Volume Matters: Longitudinal Retrospective Cohort Study of Outcomes Following Consultation and Standardization of Adrenal Surgery.

PURPOSE: Subspecialization of adrenal surgery through regionalization has not been adequately evaluated. We assessed implementation of subspecialization and the association of regionalization with adrenalectomy outcomes in a community-based setting. METHODS: In this longitudinal retrospective cohort study, we used an interrupted time series analysis on consecutive adrenal surgeries at Kaiser Permanente Northern California, 2010-2019. The intervention was regionalization of surgery in 2016. Main outcomes include surgical volumes, operative time, length of stay, 30-day return-to-care, and 30-day complications obtained from the electronic medical record. t-Tests and multivariable models were used to analyze time trends in outcomes after accounting for changes in patient and disease characteristics. RESULTS: In total, 850 adrenal surgery cases were eligible. Between 2010 and 2019, the annual incidence of surgery (per 100,000 persons) increased from 2.4 (95% CI 1.9-3.1) to 4.1 (95% CI 3.5-4.8). Average annual surgeon volume increased from 2.4 (95% CI 1.6-3.1) to 9.9 (95% CI 4.9-14.9), while hospital volume increased from 3.5 (95% CI 2.3-4.6) to 15.4 (95% CI 6.9-24.0). Operative time was 34 (23-45) min faster in 2018-2019 compared with 2010-2011. After regionalization, same-day discharges increased to 64% in 2019 (p < 0.0001). The frequency of return-to-care (p = 0.69) and the overall complication rate (p = 0.31) did not change. CONCLUSIONS: Regionalizing adrenal surgery through surgical subspecialization and standardized care pathways was feasible and decreased operative time, and hospital stay, while increasing the frequency of same-day discharges without increasing return-to-care or complications.

Higher rate of BRAF mutation in papillary thyroid cancer over time: a single-institution study.

BACKGROUND: The incidence of thyroid cancer has doubled over the past decade. The reason for this dramatic increase in incidence is controversial. Some investigators have suggested that the increased incidence is because of increased detection of small primary tumors as a result of diagnostic scrutiny. Conversely, some investigators have demonstrated an increased incidence across all tumor sizes, suggesting that other factors may play a role. This study was undertaken to investigate the clinical, pathologic, and molecular changes present in papillary thyroid cancer over a 15-year period during which the incidence of papillary thyroid cancer doubled. METHODS: A total of 628 patients with conventional papillary thyroid cancer and 228 tumor samples from a single institution were analyzed from 1991 to 2005. Time-trend analyses of demographic, clinical, pathologic, and tumor genotype were performed over three 5-year time periods: group I (1991-1995), group II (1996-2000), and group III (2001-2005). RESULTS: The authors found no differences in age, sex, ethnicity, primary tumor size, rate of extrathyroidal invasion, or overall TNM cancer stage among the 3 time groups. The rate of BRAF V600E mutation was significantly higher in group III (88% BRAF V600E positive) as compared with groups I and II (51% and 43%, respectively) (P < .001). The rate of all the common somatic mutations was also significantly higher in group III (92% positive) as compared with groups I and II (68% and 64%, respectively) (P < .002). CONCLUSIONS: The rate of BRAF V600E mutation increased significantly over a 15-year period at the authors' institution. The findings suggest that a higher rate of BRAF mutation in papillary thyroid cancer may contribute to the increasing incidence of thyroid cancer.

Identification of differentially expressed microRNA in parathyroid tumors.

BACKGROUND: The molecular factors that control parathyroid tumorigenesis are poorly understood. In the absence of local invasion or metastasis, distinguishing benign from malignant parathyroid neoplasm is difficult on histologic examination. We studied the microRNA (miRNA) profile in normal, hyperplastic, and benign and malignant parathyroid tumors to better understand the molecular factors that may play a role in parathyroid tumorigenesis and that may serve as diagnostic markers for parathyroid carcinoma. METHODS: miRNA arrays containing 825 human microRNAs with four duplicate probes per miRNA were used to profile parathyroid tumor (12 adenomas, 9 carcinomas, and 15 hyperplastic) samples normalized to four reference normal parathyroid glands. Differentially expressed miRNA were validated by real-time quantitative TaqMan polymerase chain reaction (PCR). RESULTS: One hundred fifty-six miRNAs in parathyroid hyperplasia, 277 microRNAs in parathyroid adenoma, and 167 microRNAs in parathyroid carcinomas were significantly dysregulated as compared with normal parathyroid glands [false discovery rate (FDR) < 0.05]. By supervised clustering analysis, all parathyroid carcinomas clustered together. Three miRNAs (miR-26b, miR-30b, and miR-126*) were significantly dysregulated between parathyroid carcinoma and parathyroid adenoma. Receiver-operating characteristic curve analysis showed mir-126* was the best diagnostic marker, with area under the curve of 0.776. CONCLUSIONS: Most miRNAs are downregulated in parathyroid carcinoma, while in parathyroid hyperplasia most miRNAs are upregulated. miRNA profiling shows distinct differentially expressed miRNAs by tumor type which may serve as helpful adjunct to distinguish parathyroid adenoma from carcinoma.

Prospective randomized trial of ligasure versus harmonic hemostasis technique in thyroidectomy.

BACKGROUND: Two surgical devices have become popular in thyroid surgery: a bipolar energy sealing system (B) and ultrasonic coagulation (UC). Retrospective and prospective studies have demonstrated that the use of these surgical devices for thyroidectomy compared with conventional thyroidectomy (clamp-and-tie) techniques reduces operative time and cost. We conducted a prospective randomized clinical trial to determine if there is any difference in operative time and cost between B and UC. MATERIALS AND METHODS: A single-blinded prospective randomized controlled trial was conducted at a tertiary referral center. A total of 90 patients who required a thyroidectomy for thyroid cancer, thyroid nodules, or hyperthyroidism were randomized to either B or UC during thyroidectomy. The operative time and cost of thyroidectomy were compared between the two groups. RESULTS: There was no statistically significant difference in patient age, gender, body mass index, indication for thyroidectomy and thyroid gland weight between the two groups. There was no statistically significant difference in operating room cost or total cost for thyroidectomy between the B and UC groups. There was also no statistically significant difference in the operative time between the B and UC groups (187.6 vs. 184.2 min, P = 0.48) or in postoperative complication rates. The only statistically significant difference in total cost was between surgeons independent of the device used (P < 0.01). CONCLUSIONS: In thyroid surgery, total cost and operative time were similar between the two surgical devices used.

Expression profiling of difficult-to-diagnose thyroid histologic subtypes shows distinct expression profiles and identify candidate diagnostic microRNAs.

BACKGROUND: The incidence of thyroid cancer is increasing worldwide. The findings of up to 30% of thyroid fine-needle aspiration biopsies (FNAB) are inconclusive, primarily as a result of several thyroid histologic subtypes with overlapping cytologic features. MicroRNAs (miRNAs) are small noncoding RNAs and have been implicated in carcinogenesis. We hypothesized that there are miRNAs that are differentially expressed between benign and malignant thyroid tumors that are difficult to distinguish by FNAB. METHODS: The expression of 1263 human miRNAs was profiled in 47 tumor samples representing difficult to diagnose histologic subtypes of thyroid neoplasm (21 benign, 26 malignant). Differentially expressed miRNAs were validated by quantitative real-time reverse transcriptase-polymerase chain reaction. The area under the receiver operating characteristic curve (AUC) was used to determine the diagnostic accuracy of differentially expressed miRNAs. RESULTS: Supervised hierarchical cluster analysis demonstrated grouping of 2 histologies (papillary and follicular thyroid carcinoma). A total of 34 miRNAs were differentially expressed in malignant compared to benign thyroid neoplasms (P<0.05). A total of 25 of the 34 nonproprietary miRNAs were selected for validation, and 15 of the 25 miRNAs were differentially expressed between benign and malignant samples with P-value<0.05. Seven miRNAs had AUC values of >0.7. miR-7 and miR-126 had the highest diagnostic accuracy with AUCs values of 0.81 and 0.77, respectively. CONCLUSION: To our knowledge, this is the first study to evaluate the diagnostic accuracy of miRNAs in thyroid histologies that are difficult to distinguish as benign or malignant by FNAB. miR-126 and miR-7 had high diagnostic accuracy and could be helpful adjuncts to thyroid FNAB.

Thyroid cancer gender disparity.

Cancer gender disparity in incidence, disease aggressiveness and prognosis has been observed in a variety of cancers. Thyroid cancer is one of the fastest growing cancer diagnoses worldwide. It is 2.9-times more common in women than men. The less aggressive histologic subtypes of thyroid cancer are more common in women, whereas the more aggressive histologic subtypes have similar gender distribution. The gender disparity in incidence, aggressiveness and prognosis is well established for thyroid cancer but the cause of the disparity is poorly understood. The aim of this article is to evaluate the current evidence on the cause of thyroid cancer gender disparity. Dietary and environmental factors do not appear to have a significant role in thyroid cancer gender disparity. Common somatic mutations in BRAF, rearranged in transformation/papillary thyroid carcinomas (RET/PTC) and neurotrophin receptor-tyrosine kinase (NTRK) also do not account for the gender disparity in thyroid cancer. While reproductive factors would seem a logical hypothesis to account for the gender disparity, there appears to be no conclusive effect on the risk of developing thyroid cancer. Recent studies on estrogen receptor status in thyroid cancer show a difference in the receptor subtypes expressed based on the histology of thyroid cancer. Moreover, the response to estrogen is dependent on the specific estrogen receptor expressed in thyroid cancer cells. However, what determines the tumor-specific sex hormone receptor expression is unclear. No established molecular factors appear to explain gender differences in thyroid cancer. Therefore, the application of high-throughput genomic and proteomic approaches to the study of thyroid cancer gender disparity could be helpful for better understanding the molecular basis for gender differences in thyroid and other cancers.

Rapid Implementation of Intraoperative Ultrasonography to Reduce Wire Localization in The Permanente Medical Group.

CONTEXT: Preoperative wire localization (WL), the most common localization technique for nonpalpable breast lesions, has drawbacks including scheduling constraints, cost, and patient discomfort. OBJECTIVE: To reduce WL use in our health care system, we investigated using hydrogel clips to facilitate intraoperative ultrasonography-guided lumpectomies. DESIGN: We retrospectively reviewed electronic medical records of patients with nonpalpable, ultrasound-visible breast lesions who underwent lumpectomy by 7 surgeons at 4 pilot sites in Kaiser Permanente Northern California between January 2015 and October 2015. Hydrogel clips, used for several years before the study period, were placed routinely during core-needle biopsy in all patients with nonpalpable, ultrasound-visible breast lesions. MAIN OUTCOME MEASURES: Localization method, lesion size, margin positivity, and receipt of neoadjuvant therapy. RESULTS: One hundred forty-three patients underwent hydrogel clip placement and lumpectomy by pilot-site surgeons. Localization consisted of intraoperative ultrasonography alone, preoperative skin marking, or WL. Of the 143 patients, 71.3% did not need WL (60.8% ultrasonography alone and 10.5% skin marking). The non-WL and WL groups had similarly sized lesions, and the positive margin rate was 7.2% overall, with no significant difference between the non-WL and WL groups (5.9% vs 11.5%, p = 0.33). Of the 12 patients who underwent neoadjuvant chemotherapy, 8 (67%) did not require WL. CONCLUSION: A multifacility protocol using intraoperative ultrasonography to visualize hydrogel clips was implemented, which decreased WL procedures and produced no significant difference in margin positivity between the WL and non-WL groups. This technique can be a cost-effective alternative to WL in patients who are candidates for hydrogel clip placement.

Validation of the ICON-S staging for HPV-associated oropharyngeal carcinoma using a pre-defined treatment policy.

OBJECTIVES: To determine whether the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) for HPV associated oropharyngeal carcinoma (HPV+OPC) is a better discriminator of overall survival (OS), compared with the 7th edition (7th Ed) AJCC/UICC TNM staging following curative radiotherapy (RT). MATERIAL AND METHODS: The 5-year OS for all patients with non-metastatic (M0) p16-confirmed OPC treated between 2005 and 2015 was determined and grouped based on the 7th Ed AJCC/UICC TNM and ICON-S staging. RESULTS: A total of 279 patients met the inclusion criteria. The 5-year OS with the 7th Ed TNM classification were Stage I/II 88.9% (95% CI; 70.6-100%), Stage III 93.8% (95% CI; 85.9-100%), Stage IVa 86.4% (95% CI; 81.6-91.5%) and Stage IVb 62.3% (95% CI; 46.8-82.8%). On multivariate Cox regression analysis there was no statistically significant OS difference when comparing Stage I/II with, Stage III (p=0.98, HR=0.97, 95% CI; 0.11-8.64), IVa (p=0.67, HR=1.56, 95% CI; 0.2-11.94) and IVb (p=0.11, HR=5.54, 95% CI; 0.69-44.52), respectively. The 5-year OS with ICON-S staging were Stage I 93.6% (95% CI; 89.4-98.0%), Stage II 81.9% (95% CI; 73.7-91.1%) and Stage III 69.1% (95%; 57.9-82.6%). There was a consistent decrease of OS with increasing stage. On multivariate Cox regression analysis, when compared to Stage I, OS was significantly lower for stage II (p=0.007, HR=2.84, 95% CI; 1.33-6.05) and stage III (p<0.001, HR=3.78, 95% CI; 1.81-7.92), respectively. CONCLUSION: The ICON-S staging provides better OS stratification for HPV+OPC following RT compared with the 7th Ed TNM staging.

In vitro prediction of breast cancer therapy toxicity.

BACKGROUND: Understanding the basis of clinical radiosensitivity is a key goal of radiation research. In this study, we used the limiting dilution assay (LDA) to analyze in vitro radiosensitivity of cell lines from individuals with breast and other cancers, who had been treated with ionizing radiation, and who either had a non-radiosensitive (RS) radiation response or who were clinically RS. METHODS: Lymphoblastoid cell lines (LCLs) were created from 29 cancer patients including 19 RS patients, 10 controls who had not developed severe normal tissue reactions, and 1 ataxia telangiectasia RS control cell line. The clinically RS patients had grade 3 or grade 4 reactions; one had a grade 2 reaction. All cells were exposed to graded doses of gamma-radiation in vitro and cell survival assessed via LDA. Cell survival was expressed on non-linear regression analysis-fitted survival curves and also as the surviving fraction at 2 Gray (Gy) (SF2). RESULTS: Our LDA analysis yielded two notable positive results. Firstly, it could distinguish control cells from cells from pooled breast cancer cases with severe reactions of all types (acute reactors, consequential late reactors and late reactors). Secondly, two radiosensitivity outliers were detected on the fitted curves, corresponding clinically to grade 3 and 4 late radiation reactions in breast and head and neck cancer cases respectively. The assay showed considerable cell survival heterogeneity. CONCLUSIONS: The LDA as used here may provide unique clinical utility in detecting potential RS breast cancer patients prior to radiotherapy (RT), a form of personalized medicine. The assay may be especially useful in situations where its results can be temporally available prior to therapy initiation (e.g., those patients not undergoing RT until some months after surgery, typically those having adjuvant chemotherapy prior to RT). Two LCLs from RS outliers could potentially yield insight into the cellular and/or genetic basis of radiosensitivity, for example by undertaking genomic analyses on these cell lines.

Definitive intensity-modulated radiotherapy concurrent with systemic therapy for oropharyngeal squamous cell carcinoma: Outcomes from an integrated regional Australian cancer centre.

INTRODUCTION: Oropharyngeal squamous cell carcinoma (OPSCC) incidence has increased over the past two decades largely because of an increase in human papilloma virus (HPV)-related OPSCC. We report here outcomes of definitive radiation therapy for OPSCC with simultaneous integrated boost intensity-modulated radiotherapy (IMRT) in a regional Australian cancer centre. METHODS: We retrospectively reviewed electronic medical records (EMR) of all patients treated with IMRT for head and neck cancer. We included patients who received a curative intent IMRT for OPSCC (2010-2014). RESULTS: Of 61 patients, 80% were men, and the median age was 57 years. Ninety percent of our patients received concurrent systemic therapy, and 68% were p16 positive. The median radiotherapy dose received was 70 Gy in 35 fractions. The median follow up for surviving patients was 22 months. Twenty-four month actuarial data show that the loco-regional recurrence free, metastasis-free MFS, cancer-specific (CaSS) and overall survival percentages were 98.3%, 92.6%, 91% and 90.3%, respectively. We did not observe grades 4 or 5 acute or late toxicities, and 10 patients (16.2%) exhibited persistent grade 3 toxicity 6 months after completing the treatment. CONCLUSION: The results from curative IMRTs for OPSCC delivered in a regional cancer centre are comparable with results published by tertiary referral centres. A long-term follow up of this patient cohort will continue for further analyses and comparisons with tertiary centres.

RTN4IP1 is down-regulated in thyroid cancer and has tumor-suppressive function.

CONTEXT: Previously we identified RTN4IP1 to be differentially expressed in thyroid cancer by sex and the gene is located on chromosome 6q21, a chromosomal region frequently deleted or with loss of heterozygosity in a variety of human malignancies including thyroid cancer. OBJECTIVE: Because the expression and function of this gene is unknown, we sought to characterize its expression in normal, hyperplastic, and benign and malignant thyroid tissue samples and to evaluate its function in cancer cells. DESIGN: RTN4IP1 expression was analyzed in normal and hyperplastic thyroid tissue and benign and malignant thyroid tissue samples. In 3 thyroid cancer cell lines (TPC1 from a papillary thyroid cancer, FTC133 from a follicular thyroid cancer, XTC1 from a Hürthle cell carcinoma), small interfering RNA knockdown of RTN4IP1 was used to determine its role in regulating the hallmarks of malignant cell phenotype (cellular proliferation, migration, apoptosis, invasion, tumor spheroid formation, anchorage independent growth). RESULTS: We found RTN4IP1 mRNA expression was significantly down-regulated in follicular and papillary thyroid cancer as compared with normal, hyperplastic, and benign thyroid neoplasms (P < .05). Moreover, RTN4IP1 mRNA expression was significantly lower in larger papillary thyroid cancers (P < .05). Small interfering RNA knockdown of RTN4IP1 expression increased cellular proliferation (2- to 4-fold) in all 3 of the cell lines tested and increased cellular invasion (1.5- to 3-fold) and migration (2- to 7.5-fold), colony formation (3- to 6-fold), and tumor spheroid formation (P < .05) in 2 of the 3 cell lines tested (FTC-133 and XTC1). CONCLUSIONS: This is the first study to characterize the expression and function of RTN4IP1 in cancer. Our results demonstrate RTN4IP1 is down-regulated in thyroid cancer and is associated with larger papillary thyroid cancer and that it regulates malignant cell phenotype. These findings, taken together, suggest that RTN4IP1 has a tumor-suppressive function and may regulate thyroid cancer progression.

Emerging understanding of dosimetric factors impacting on dysphagia and nutrition following radiotherapy for oropharyngeal cancer.

BACKGROUND: Research has reported relationships between 3-dimensional (3D) radiation dose to head and neck structures and consequential swallowing/nutritional outcomes. However, this evidence is preliminary. The current study aimed to identify which reported dose constraints identified functional impairment at 6 months posttreatment. METHODS: Dose constraints with reported relationships to swallowing and nutrition were identified through a systematic literature review. Dose-volume histograms for 12 patients with T1-T3 oropharyngeal cancer treated with 3D conformal radiotherapy determined dosages delivered to specific structures. Doses were examined in relation to published dose constraints and the swallowing and nutritional outcomes at 6 months posttreatment. RESULTS: In all, 66% of the reported mean, maximum, and partial doses to 8 structures correctly identified swallowing and nutrition outcomes at 6 months. CONCLUSION: The relationships observed between known dosimetric constraints and functional outcomes highlight the potential for dosimetric data to assist in prognosis and treatment. Systematic research is required to refine dosimetric parameters and the impact on functional outcomes.

Evaluation of candidate diagnostic microRNAs in thyroid fine-needle aspiration biopsy samples.

BACKGROUND: Thyroid cancer diagnosis in the United States has increased by 2.3-folds in the last three decades. Up to 30% of thyroid fine-needle aspiration biopsy (FNAB) results are inconclusive. Several differentially expressed microRNAs (miRNAs) have been identified as candidate diagnostic markers for thyroid nodules. We hypothesized that these differentially expressed miRNAs may improve the accuracy of FNAB in difficult to diagnose thyroid nodules. METHODS: Expression levels of four miRNAs (miR-7, -126, -374a, and let-7g) were analyzed using quantitative real-time reverse transcription-polymerase chain reaction in 95 FNAB samples as the training set. A predictor model was formulated based on the most differentially expressed miRNA (miR-7) ΔCt value and the model was applied on a separate cohort of 59 FNAB samples as the validation set. RESULTS: miR-7 was the best predictor to distinguish benign from malignant thyroid FNAB samples. The other three miRNAs were co-expressed and did not significantly contribute to the predictor model. miR-7 had a sensitivity of 100%, specificity of 29%, positive predictive value (PPV) of 36%, negative predictive value (NPV) of 100%, and overall accuracy of 76% when applied to the validation set. In subgroup analysis of preoperative nondiagnostic, indeterminate, or suspicious FNAB samples, the predictor model had an overall accuracy of 37% with sensitivity of 100%, specificity of 20%, PPV of 25%, and NPV of 100%. CONCLUSIONS: miR-7 may be a helpful adjunct marker to thyroid FNAB in tumor types which are inconclusive. Given the high NPV of miR-7, a patient with a benign result based on the predictor model may be followed as opposed to performing an immediate diagnostic thyroidectomy. Future prospective clinical trials evaluating its accuracy in a larger cohort are warranted to determine its clinical utility.

CDC23 regulates cancer cell phenotype and is overexpressed in papillary thyroid cancer.

Cancer gender disparities have been observed for a variety of human malignancies. Thyroid cancer is one such example where there is a dramatic difference in the incidence, aggressiveness, and death rate by gender. The molecular basis for gender disparity is poorly understood. To address this, we performed genome-wide gene expression profiling in matched papillary thyroid cancer (PTC) samples and identified nine candidate genes differentially expressed by gender. One of these genes was CDC23 that was upregulated in PTC in men compared with women. Because the function and expression of CDC23 is unknown in eukaryotic cells, we further characterized the expression of CDC23 in normal, hyperplastic, and PTC tissue samples. We found CDC23 was overexpressed in PTC and absent in normal and hyperplastic thyroid tissue. In thyroid cancer cells, functional knockdown of CDC23 resulted in an increase in the number of cells in both the S and G(2)M phases of the cell cycle, and an inhibition of cellular proliferation, tumor spheroid formation, and anchorage-independent growth. Cellular arrest in both S and G(2)M phases was associated with significant cyclin B1 and securin protein accumulation after CDC23 knockdown. Moreover, the effect of CDC23 on cellular proliferation and cell cycle progression was reversed on triple knockdown studies of CDC23, cyclin B1, and securin. Our data taken together suggests CDC23 has important biologic effects on cell proliferation and cell cycle progression. The effect of CDC23 on cellular proliferation and cell cycle progression is mediated, at least in part, by cyclin B1 and securin protein levels. Therefore, we propose that CDC23 is a critical regulator of cell cycle and cell growth, and may be involved in thyroid cancer initiation and progression, and may explain the different tumor biology observed by gender.

Comparison of 6-18F-fluoro-L-DOPA, 18F-2-deoxy-D-glucose, CT, and MRI in patients with pancreatic neuroendocrine neoplasms with von Hippel-Lindau disease.

INTRODUCTION: There are limited data on the utility of 6-(18)F-fluoro-l-3,4-dihydroxyphenylalanine ((18)F-DOPA) and (18)F-2-deoxy-d-glucose ((18)F-FDG) in the workup of patients with pancreatic neuroendocrine tumors (PNETs). The aim of our study was to determine the accuracy of (18)F-DOPA and (18)F-FDG to detect PNETs in patients with von Hippel-Lindau disease (vHL). METHODS: We studied prospectively 69 patients with a diagnosis of vHL and pancreatic lesion(s) using computed tomography (CT), magnetic resonance imaging (MRI), (18)F-FDG, and (18)F-DOPA. Clinical, genetic, and laboratory characteristics were analyzed to determine association with imaging study results. RESULTS: In sum, 40 patients underwent evaluation by all 4 modalities; 98 PNETs and 55 PNETs were identified on CT and MRI, respectively. Only 11 of the 98 lesions (11%) were positive on (18)F-DOPA and 45 of the 98 (46%) lesions were positive on (18)F-FDG. There were 13 (18)F-DOPA and 26 (18)F-FDG avid extrapancreatic lesions. One patient underwent resection of an (18)F-DOPA avid extrapancreatic lesion in the lung, with pathology demonstrating a NET. There was no association between (18)F-DOPA and (18)F-FDG avidity and tumor size, age, gender, vHL mutation, or serum chromogranin A level. CONCLUSION: (18)F-FDG and MRI may be adjuncts to CT in identifying PNETs and metastatic disease. (18)F-DOPA has limited value in identifying PNETs in patients with vHL, but may be useful for identifying extrapancreatic NET lesions.

Prior head and neck radiation exposure is not a contraindication to minimally invasive parathyroidectomy.

BACKGROUND: Most patients with primary hyperparathyroidism can have a minimally invasive parathyroidectomy based on localization studies showing single-gland disease. In patients with a history of head and neck irradiation, due to the increased risk of multigland disease and risk of concurrent thyroid cancer, minimally invasive parathyroidectomy is considered by some to be a contraindication. We postulated that previous history of head and neck irradiation should not be a contraindication for minimally invasive parathyroidectomy and tested this hypothesis in a prospective cohort of patients undergoing parathyroidectomy for primary hyperparathyroidism. STUDY DESIGN: We performed a retrospective analysis of a prospective database of 491 consecutive parathyroidectomies performed between May 2005 and May 2007 at a tertiary referral medical center. RESULTS: Fifty-two (12.6%) patients had a history of head and neck irradiation and 360 (87.4%) had no exposure to radiation. The 2 groups had no significant difference in terms of gender or ethnicity. The radiation group was older, with an average age of 65.1 years versus 58.1 years (p < 0.0009). There was no significant difference in concurrent benign thyroid neoplasm, thyroid cancer, and type of parathyroid disease (single vs multigland) in the 2 groups. There was no significant difference in the operative approach used between the 2 groups (focused vs unilateral or bilateral). CONCLUSIONS: Head and neck irradiation should not be a contraindication for minimally invasive parathyroidectomy in patients with primary hyperparathyroidism in the setting of preoperative localization studies showing single-gland disease and no concurrent thyroid neoplasm. Furthermore, history of head and neck irradiation is associated with a later age of presentation for parathyroidectomy.