Avital Harari

Objective: To examine environmental factors that influence risk of thyroid cancer. Methods: We performed a case-control study utilizing thyroid cancer cases from the California Cancer Registry (1999-2012) and controls sampled in a population-based manner. Study participants were included if they were diagnosed with thyroid cancer, lived in the study area at their time of diagnosis, and were ≥35 years of age. Controls were recruited from the same area and eligible to participate if they were ≥35 years of age and had been living in California for at least 5 years prior to the interview. We examined residential exposure to 29 agricultural use pesticides, known to cause DNA damage in vitro or are known endocrine disruptors. We employed a validated geographic information system–based system to generate exposure estimates for each participant. Results: Our sample included 2067 cases and 1003 controls. In single pollutant models and within a 20-year exposure period, 10 out of 29 selected pesticides were associated with thyroid cancer, including several of the most applied pesticides in the United States such as paraquat dichloride [odds ratio (OR): 1.46 (95% CI: 1.23, 1.73)], glyphosate [OR: 1.33 (95% CI: 1.12, 1.58)], and oxyfluorfen [OR: 1.21 (95% CI: 1.02, 1.43)]. Risk of thyroid cancer increased proportionately to the total number of pesticides subjects were exposed to 20 years before diagnosis or interview. In all models, paraquat dichloride was associated with thyroid cancer. Conclusions: Our study provides first evidence in support of the hypothesis that residential pesticide exposure from agricultural applications is associated with an increased risk of thyroid cancer.

Four-dimensional computed tomography (4DCT) is an emerging imaging modality in the evaluation of primary hyperparathyroidism (PHPT). We assessed the role of 4DCT in patients presenting for reoperative parathyroidectomy. A prospective database of patients with persistent or recurrent PHPT undergoing reoperative parathyroidectomy during the years 2006–2014 was analyzed. Patients treated before versus after the advent of 4DCT were compared for operative eligibility, operative success, operative time, and concordance of imaging results with surgical findings. Ninety patients were included in the study (61 before 4DCT, 29 after 4DCT). The post-4DCT group had a higher rate of surgical concordance with imaging results (63 vs. 90 %, p < 0.01) and shorter operative time (114 vs. 76 min, p < 0.05). The operative success rate was not different (87 vs. 86 %). A similar pattern was observed in the subset of sestamibi-negative patients, with post-4DCT patients having a higher rate of surgical concordance (12 vs. 83 %, p < 0.0001) and shorter operative time (181 vs. 89 min, p < 0.05). Among patients ultimately found to have parathyroid hyperplasia, 4DCT correctly identified multiple enlarged glands in 80 % (4 of 5) and correctly lateralized one or more glands in 100 % (5 of 5) of cases, facilitating successful subtotal parathyroidectomy in the reoperative setting. 4DCT enables successful and efficient reoperative parathyroidectomy. These benefits extend to difficult cases, including sestamibi-negative patients and those with missed hyperplasia.

Background: A higher body mass index (BMI) is associated with more advanced stages of thyroid cancer. Screening obese patients for thyroid cancer has been proposed but has yet to be examined for cost-effectiveness. The objective of this study was to assess the cost-effectiveness of ultrasound (US) screening of obese patients for thyroid cancer. Methods: A decision-tree model compared cost savings for the following: (i) base case scenario of an obese patient with thyroid nodule found by palpation, (ii) universal US screening of all obese patients, and (iii) risk-based US screening in obese patients. Risk-based screening consisted of patients who had at least one of four major identified risk factors for thyroid cancer (family history of thyroid cancer, radiation exposure, Hashimoto's thyroiditis, and/or elevated thyrotropin). Patients with nodules underwent established treatment and management guidelines. The model accounted for recurrence, complications, and long-term treatment/follow-up for five years. Outcome probabilities were identified from a literature review. Costs were estimated using a third-party payer perspective. Sensitivity analyses were performed to examine the impact of risk factor prevalence and US cost on the model. Results: The resulted costs per patient were $210.73 in the base case scenario, $434.10 in the universal US screening arm, and $166.72 in the risk-based screening arm. Risk-based screening remained cost-effective until more than 14% of obese patients had risk factors and with a wide variation of US costs ($0–$1113). Conclusion: Risk-based US screening in selected obese patients with risk factors for thyroid cancer is cost-effective. Recommendations for screening this subgroup will result in cost savings and a likely decreased morbidity and mortality in this subpopulation with more aggressive disease.

Thyroglobulin antibodies (TgAb) are present in approximately 20% of patients with papillary thyroid cancer (PTC) and invalidate the serum thyroglobulin (Tg) level as a tumour marker. We examined whether trends in the TgAb level could serve as a surrogate marker of disease status in the surveillance of patients with PTC. All patients found to have a least one positive postoperative TgAb level (determined by the Beckman-Coulter Access Assay) after undergoing initial surgery for PTC from 2000 to 2010 at a single institution were included. Log-log transformation and linear regression were applied to longitudinal TgAb levels, yielding patient-specific regression coefficients that categorized as follows: highly negative, moderately negative and positive/no trend. The recurrence rate in each category was then assessed. Ninety-three of 967 patients with PTC were included. Recurrent disease was detected in 19 patients (20%) after a mean follow-up time of 51 months. Regression coefficients in the highly negative and moderately negative groups were not different, and hence these groups were pooled. The proportion of recurrent cases in the negative trend group was similar to that in the positive/no trend group (19.7% vs 21.9%, NS). The mean regression coefficients were similar for recurrent and nonrecurrent cases within both the negative trend group (-0.89 vs -0.80, NS) and the positive/no trend group (0.08 vs 0.33, NS). Trends in the TgAb level do not predict disease status in PTC in our experience. In the context of most commercially available TgAb assays, surveillance of TgAb-positive patients will hinge on high-quality imaging until a valid alternative serum marker to Tg is identified.

Context: Racial/ethnic minorities suffer disproportionate morbidity and mortality from chronic diseases. Objective: Our objective was to assess racial and socioeconomic status (SES) disparities in well-differentiated thyroid cancer (WDTC) patients. Design and Participants: We conducted a retrospective cohort study on 25 945 patients with WDTC (1999–2008) from the California Cancer Registry (57% white, 4% black, 24% Hispanic, and 15% Asian-Pacific Islander [API]). Main Outcomes: We evaluated effect of race and SES variables on stage of cancer presentation and overall/disease-specific survival. Results: Significant differences in stage of presentation between all racial groups were found (P < .001), with minority groups presenting with a higher percentage of metastatic disease as compared with white patients (black, odds ratio [OR] = 1.36 with confidence interval [CI] 1.01–1.84; Hispanic, OR = 1.89 [CI, 1.62–2.21], API, OR = 1.82 [CI, 1.54–2.15]). Hispanic (OR = 1.59, [CI, 1.48–1.72]) and API (OR = 1.32 [1.22–1.44]) patients also presented with higher odds of regional disease. Patients with the lowest SES presented with metastatic disease more often than those with the highest SES (OR = 1.45 [CI, 1.16–1.82]). Those that were poor/uninsured and/or with Medicaid insurance had higher odds of presenting with metastatic disease as compared with those with private insurance (OR = 2.41, [CI, 2.10–2.77]). Unadjusted overall survival rates were higher among API and Hispanic patients and lower among black patients (P < .001 vs white patients). Adjusted overall survival also showed a survival disadvantage for black patients (hazard ratio = 1.4, [CI, 1.10–1.73]) and survival advantage for API patients (hazard ratio = 0.83, [CI, 0.71–0.97]). In disease-specific survival analyses, when only those patients with metastatic disease were analyzed separately, black patients again had the lowest survival rates, and Hispanic/API patients had the highest survival rates (P < .04). Conclusion: Black patients and those with low SES have worse outcomes for thyroid cancer. API and Hispanic patients may have a protective effect on survival despite presenting with more advanced disease.

Reoperation in the neck can be challenging and is associated with increased complication rates and operative times. Here we analyze our methylene blue dye injection method to localize reoperative neck pathology in patients with thyroid cancer and lymph node metastases. We retrospectively reviewed the records of all patients at a single university tertiary care center who had reoperative neck surgery for recurrent thyroid cancer between 2004 and 2009, and who also underwent intraoperative methylene blue dye injection. Outcomes measured were efficacy and safety of the injection technique as well as complication rates. Fifty-three operations were performed in 44 patients (average age, 51.2 years [range 16 to 83 years]). Ninety-one percent (48 of 53) of the operations resulted in successful resection of recurrent disease. Of these, 96% (46 of 48) were guided successfully by blue dye injection. Thyroglobulin became undetectable in 42% (11 of 26) of patients. Neck pathology included the following thyroid cancers: papillary (48 of 53), follicular (2 of 53), medullary (2 of 53), and tall cell variant (1 of 53). Among these patients, there were a total of 26 central and 38 lateral neck dissections. The average number of previous neck dissections was 2 (range 1 to 5). The mean intraoperative ultrasound/injection time was 21.3 min (n = 13). Median operative time was 90 minutes (range 40 to 300 minutes). Complications included 2 permanent vocal cord paralyses, 1 instance of permanent hypocalcemia, and 3 instances of temporary hypocalcemia. There were no complications related to the dye injection. Intraoperative, ultrasound-guided, methylene blue dye injection is a safe and effective technique. It facilitates tumor localization and removal especially in patients requiring reoperative neck surgery.