Effect of Exposure to Agent Orange on the Risk of Monoclonal Gammopathy and Subsequent Transformation to Multiple Myeloma: A Single-Center Experience From the Veterans Affairs Hospital, Detroit.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is an indolent, premalignant plasma cell disorder with the potential of transforming into symptomatic multiple myeloma (MM). There are multiple risk factors that contribute to transformation. Agent Orange (AO) has been linked with multiple malignant and nonmalignant conditions. PATIENTS AND METHODS: We conducted a retrospective chart review of patients with monoclonal gammopathy who were seen at John D. Dingell Veterans Affairs Medical Center (Detroit, Michigan) between 2005 and 2015 with MGUS, smoldering multiple myeloma, and MM. We explored baseline patient characteristics and explored AO exposure. Dates of diagnosis, dates of progression, and expiration dates were recorded to time to progression and overall survival (OS). RESULTS: We identified 211 patients with monoclonal gammopathy; 96% were male and 122 were African American. Eleven patients had reported AO exposure. Cumulative risk of progression in the overall population was 1.4% at 1 year. Risk of transformation in the population exposed to AO was significantly higher with a hazard ratio (HR) of 11.19 (95% confidence interval [CI], 2.10-59.47; P = .005). OS was numerically shorter in AO-exposed patients with a median OS of 7 years compared with 11.1 years in those not exposed. However, AO exposure was not associated with OS in multivariable analysis (HR, 0.50; 95% CI, 0.07-3.83; P = .508). CONCLUSION: Monoclonal gammopathy is a premalignant condition with the risk of progressing to MM. Exposure to AO has been implicated in multiple conditions including MM. Our study demonstrates an increased risk of progression in exposed patients.

The Impact of Agent Orange Exposure on Prostate Cancer Outcomes.

PURPOSE: In this study we explored the effect of Agent Orange exposure on prostate cancer survival in VA (Veterans Affairs) patients receiving androgen deprivation therapy for advanced prostate cancer. MATERIALS AND METHODS: We retrospectively examined the association between Agent Orange exposure in men with prostate cancer in national VA databases who were being treated with androgen deprivation therapy. Patients were diagnosed with prostate cancer from 2000 to 2008 with followup through May 2016. Clinical, pathological and demographic variables were compared by Agent Orange exposure. Associations of Agent Orange with overall survival, skeletal related events and cancer specific survival were performed using adjusted Cox proportional hazard models after IPSW (inverse propensity score weighted) adjustment. RESULTS: Overall 87,344 patients were identified. The 3,475 Agent Orange exposed patients were younger (p <0.001), had lower prostate specific antigen (p = 0.002) and were more likely to receive local therapy and chemotherapy (p <0.001) than the 83,869 nonexposed patients. The Charlson comorbidity index was similar in the groups (p = 0.40). After IPSW adjustment Agent Orange exposure was associated with improved overall survival (HR 0.84, 95% CI 0.73-0.97, p = 0.02). However, no difference was observed in the risk of skeletal related events (HR 1.04, 95% CI 0.80-1.35, p = 0.77) or cancer specific survival (HR 0.79, 95% CI 0.60-1.03, p = 0.08). CONCLUSIONS: Agent Orange exposure was associated with a decreased risk of death in men receiving androgen deprivation therapy for advanced prostate cancer. It does not appear to be associated with worse oncologic outcomes.

Jock McCulloch (1945-2018): A Tribute.

Jock William McCulloch, who died at Melbourne, Australia, in January 2018, was one of the foremost historians of occupational health of his generation. This tribute reviews his career and oeuvre, which was tragically ended by his death from mesothelioma.

Impact of presumed service-connected diagnosis on the Department of Veterans Affairs healthcare utilization patterns of Vietnam-Theater Veterans: A cross-sectional study.

During the Vietnam War, the US military sprayed almost 20 million gallons of Agent Orange (AO), an herbicide contaminated with dioxin, over Vietnam. Approximately, 2.7 million US military personnel may have been exposed to AO during their deployment. Ordinarily, veterans who can demonstrate a nexus between a diagnosed condition and military service are eligible for Department of Veterans Affairs (VA) service-connected disability compensation. Vietnam Veterans have had difficulty, however, establishing a nexus between AO exposure and certain medical conditions that developed many years after the war. In response, VA has designated certain conditions as "presumed service connected" for Vietnam Veterans who were present and possibly exposed. Veterans with any of these designated conditions do not have to document AO exposure, making it easier for them to access the VA disability system. The extent to which VA healthcare utilization patterns reflect easier access afforded those with diagnosed presumptive conditions remains unknown. In this cross-sectional study, we hypothesized that Vietnam Veterans with diagnosed presumptive conditions would be heavier users of the VA healthcare system than those without these conditions. In our analysis of 85,699 Vietnam Veterans, we used binary and cumulative logit multivariable regression to assess associations between diagnosed presumptive conditions and VA healthcare utilization in 2013. We found that diagnosed presumptive conditions were associated with higher odds of 5+ VHA primary care visits (OR = 2.01, 95% CI: 1.93-2.07), 5+ specialty care visits (OR = 2.11, 95% CI: 2.04-2.18), emergency department use (OR = 1.22, 95% CI: 1.11-1.34), and hospitalization (OR = 1.23, 95% CI: 1.17-1.29). Consistent with legislative intent, presumptive policies appear to facilitate greater VA system utilization for Vietnam Veterans who may have been exposed to AO.

HIGH PREVALENCE OF AGENT ORANGE EXPOSURE AMONG THYROID CANCER PATIENTS IN THE NATIONAL VA HEALTHCARE SYSTEM.

OBJECTIVE: Thyroid cancer is the most common endocrine malignancy and the most rapidly increasing cancer in the U.S. Little is known regarding the epidemiology and characteristics of patients with thyroid cancer within the national Veterans Health Administration (VHA) integrated healthcare system. The aim of this study was to further understand the characteristics of thyroid cancer patients in the VHA population, particularly in relation to Agent Orange exposure. METHODS: This is a descriptive analysis of the VA (Veterans Affairs) Corporate Data Warehouse database from all U.S. VHA healthcare sites from October1, 1999, to December 31, 2013. Information was extracted for all thyroid cancer patients based on International Classification of Diseases-ninth revision diagnosis codes; histologic subtypes of thyroid cancer were not available. RESULTS: There were 19,592 patients (86% men, 76% white, 58% married, 42% Vietnam-era Veteran) in the VHA system with a diagnosis of thyroid cancer within this 14-year study period. The gender-stratified prevalence rates of thyroid cancer among the Veteran population during the study period were 1:1,114 (women) and 1:1,023 (men), which were lower for women but similar for men, when compared to the U.S. general population in 2011 (1:350 for women and 1:1,219 for men). There was a significantly higher proportion of self-reported Agent Orange exposure among thyroid cancer patients (10.0%), compared to the general VHA population (6.2%) (P<.0001). CONCLUSION: Thyroid cancer patients, in this sample, have a higher prevalence of self-reported Agent Orange exposure compared to the overall national VA patient population. ABBREVIATIONS: T4 = thyroxine TCDD = 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin TSH = thyroid-stimulating hormone VA = Veterans Affairs VHA = Veterans Health Administration.