Environmental radiation exposure at Chornobyl has not systematically affected the genomes or chemical mutagen tolerance phenotypes of local worms.

The 1986 disaster at the Chornobyl Nuclear Power Plant transformed the surrounding region into the most radioactive landscape known on the planet. Whether or not this sudden environmental shift selected for species, or even individuals within a species, that are naturally more resistant to mutagen exposure remains an open question. In this study, we collected, cultured, and cryopreserved 298 wild nematode isolates from areas varying in radioactivity within the Chornobyl Exclusion Zone. We sequenced and assembled genomes de novo for 20 Oscheius tipulae strains, analyzed their genomes for evidence of recent mutation acquisition in the field, and observed no evidence of an association between mutation and radioactivity at the sites of collection. Multigenerational exposure of each of these strains to several chemical mutagens in the lab revealed that strains vary heritably in tolerance to each mutagen, but mutagen tolerance cannot be predicted based on the radiation levels at collection sites, and Chornobyl isolates were not systematically more resistant than strains from undisturbed habitats. In sum, the absence of mutational signatures does not reflect unique capacity for tolerating DNA damage.

Quality of Life After Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Oropharynx Cancer.

Importance: Efforts are underway to deintensified treatment protocols for patients with human papillomavirus virus-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) to achieve similar excellent oncologic outcomes while reducing treatment-related adverse effects. Transoral robotic surgery (TORS) as primary treatment often requires adjuvant therapy due to the high incidence of nodal metastasis. Treatment with neoadjuvant chemotherapy followed by TORS and neck dissection (NECTORS), reserving radiation therapy for salvage, yields excellent oncologic outcomes. Objective: To assess patient-reported quality of life (QOL) and functional outcomes among patients with HPV-OPSCC who undergo NECTORS. Design, Settings, and Participants: This was a multicenter prospective cohort study of patients with HPV-OPSCC treated with the NECTORS protocol in 2017 to 2022. Consecutive patients with stage III or IVa HPV-OPSCC treated with NECTORS in 2017 to 2022 who had completed the primary QOL questionnaire at baseline and at least once during the 24-month follow-up period were included. Ninety-four patients were eligible, and 67 were included in the analyses. Outcome Measures: QOL questionnaires at baseline, and at month 1, 3, 6, 12, 18, and 24 posttreatment. Global score on the 30-item European Organization for Research and Treatment of Cancer Core quality of life questionnaire (EORTC QLQ-C30) was the primary outcome; the head and neck extension module (EORTC QLQ-HN35); the MD Anderson Dysphagia Inventory for dysphagia-related QOL; and the Decision Regret Scale were also used. Paired t tests assessed change between the baseline and 12- or 24-month patient-reported outcomes. Results: Among the study population of 67 patients (median [range] age, 63 [58-67] years; 54 [80.6%] male) with HPV-OPSCC, the most frequent cancer subsites were palatine tonsil (41 [61%]) and base of tongue (26 [39%]); none required adjuvant RT. Global QOL at 24 months improved compared with baseline (mean difference, 9.49; 95% CI, 2.45 to 16.53). All EORTC QLQ-C30 functional scores returned to baseline or improved within 3 to 6 months posttreatment and remained stable at 24 months. EORTC QLQ-HN35 symptom scale scores improved or were stable at 24 months. The MD Anderson Dysphagia Inventory scores demonstrated no significant difference between baseline and month 12 for global scores (mean difference, 6.15; 95% CI, -4.18 to 16.49) and composite scores (mean difference, 2.73; 95% CI, -1.62 to 7.09). Median (range) score on the Decision Regret Scale was 5 of 100 (0-30), representing mild overall regret. Conclusion and Relevance: The findings of this multicenter cohort study indicate that use of the NECTORS protocol is associated with excellent QOL outcomes. QOL measures returned to baseline levels or were better than baseline, which represents positive outcomes for patients with HPV-OPSCC who undergo this treatment regimen.

Environmental radiation exposure at Chornobyl has not systematically affected the genomes or mutagen tolerance phenotypes of local worms.

The 1986 disaster at the Chornobyl Nuclear Power Plant transformed the surrounding region into the most radioactive landscape known on the planet. Questions remain regarding whether this sudden environmental shift selected for species, or even individuals within a species, that are naturally more resistant to radiation exposure. We collected, cultured, and cryopreserved 298 wild nematodes isolates from areas varying in radioactivity within the Chornobyl Exclusion Zone. We sequenced and assembled genomes de novo for 20 Oschieus tipulae strains, analyzed their genomes for evidence of recent mutation acquisition in the field and saw no evidence of an association between mutation and radiation level at the sites of collection. Multigenerational exposure of each of these strains to several mutagens in the lab revealed that strains vary heritably in tolerance to each mutagen, but mutagen tolerance cannot be predicted based on the radiation levels at collection sites.

Metastatic Clear Renal-Cell Carcinoma Mimicking Anaplastic Thyroid Cancer: A Case Report.

Metastatic renal cell carcinoma to the thyroid is a rare yet aggressive histopathologic diagnosis, which may often be omitted from the initial clinical differential. This is in part due to the long latency period between the initial renal primary and appearance of metastatic disease, coupled with the diagnostic limitations of fine-needle aspiration biopsies. We herein present an interesting case of a metastatic clear-cell renal-cell carcinoma mimicking an aggressive primary thyroid neoplasm, 10 years after a nephrectomy for a renal primary, highlighting key diagnostic and management considerations.

High-Grade Neuroendocrine Carcinoma Within a Tracheal Polyp: A Case Report.

INTRODUCTION: Primary carcinomas of the trachea are rare, with a reported annual incidence of one in a million. We present a case of a previously undescribed polypoid high-grade neuroendocrine carcinoma of the trachea. Resection of the carcinoma revealed only superficial invasion of the mucosa and without evidence of local or distant metastatic disease. Histologically, the tumor had high-grade features with necrosis and a high mitotic index. METHODS: Characterization of this rare neuroendocrine carcinoma of the trachea was performed by immunohistochemistry and whole-genome sequencing. RESULTS: Immunohistochemistry result was positive for neuroendocrine markers, p16 and an elevated Ki-67. Whole-genome sequencing of the lesion was performed and revealed a very unusual and very distinct mutational signature without relationship to other relevant neuroendocrine carcinomas. Neither known driver nor targetable mutations were found by whole-genome sequencing. Analysis of the sequence of numerous viral elements of human papillomavirus-18 suggests that the pathogenesis of the lesion is related to viral integration. The patient developed distal recurrence, which progressed to widespread pulmonary dissemination, presumably through aerogenous spread of disease. CONCLUSIONS: This is the first characterization of this type of tracheal tumor, including genomic findings, pathogenesis, and natural history.

Evidence-based diagnostic accuracy measurement in urine cytology using likelihood ratios.

INTRODUCTION: Recent cytology classification systems have become more evidence-based and advocate for the use of risk of malignancy (ROM) as a measure of test performance. From the statistical viewpoint, ROM represents the post-test probability of malignancy, which changes with the test result and also with the prevalence of malignancies (or pre-test probability) in each individual practice setting and individual patient presentation. Evidence-based medicine offers likelihood ratios (LRs) as a measure of diagnostic accuracy for multilevel diagnostic tests, superior to sensitivity and specificity as data binarization and information loss are avoided. LRs are used in clinical medicine and could be successfully applied to the practice of cytopathology. Our aim was to establish LRs to compare diagnostic accuracy of The Paris System for Reporting Urinary Cytology (TPS) and of a historic urine cytology reporting system. MATERIALS AND METHODS: We analyzed sequential voided urine cytology cases with histologic outcomes: 188 pre-TPS and 167 post-TPS. LRs were calculated as LR = True positive % (per category)/False positive % (per category) [95% confidence interval] and interpreted LRs = 1 nondiagnostic, LR >1 favor, LR >10 strongly favor, LRs <1 favor exclusion, and LR <0.1 strongly favor exclusion of a target condition, respectively. CATmaker open source software and Fagan nomograms were used for calculation and visualization of the corresponding post-test probability (ROM) of high-grade urothelial carcinoma (HGUC) in various scenarios. RESULTS: Both reporting systems show near-similar performance in terms of LRs, with moderate discriminatory power of negative, suspicious, and positive for HGUC test results. The atypical urothelial cell (AUC) category establishes as indiscriminate LR = 1 in the TPS, whereas in pre-TPS it favored a benign condition. We further demonstrate the utility of LRs to determine individual post-test probability (ROM) in a variety of clinical scenarios in a personalized fashion. CONCLUSIONS: The LRs allow for a quantitative performance measure in case of urine cytology across different scenarios adding numeric information on diagnostic test accuracy and post-test probability of HGUC. The diagnostic accuracy of pre-TPS and post-TPS remained similar for all but the AUC category. With the TPS, the AUC category has become genuinely diagnostically and statistically indeterminate and requires further patient investigations.

The Role of the ThyroSeq v3 Molecular Test in the Surgical Management of Thyroid Nodules in the Canadian Public Health Care Setting.

Background: Although the current gold standard for diagnosing thyroid nodule malignancy is ultrasound-guided fine-needle aspiration (FNA) cytology, about 20-25% of cytological evaluations are considered indeterminate for malignancy. This limitation has led to the emergence of next-generation sequencing panels, for example, ThyroSeq v3 (TSv3), which recognize highly diagnostic genetic mutations of common thyroid carcinomas in FNA samples and classify them as test-negative or test-positive, helping optimize treatment for indeterminate thyroid nodules (ITNs). Our goals were to evaluate the benign call rate (BCR) of TSv3 and assess its diagnostic performance and clinical utility while highlighting the points of consideration for a public Canadian institution. Methods: This is a single-center study conducted at the Royal Victoria Hospital (McGill University Health Centre) in Montreal, Canada, between January and February 2019. Patients were offered TSv3 following the McGill algorithm for ITN workup, a novel protocol developed at our institution to select only diagnostic surgery candidates to minimize waste of public resources, considering the single-payer health care system. Patient demographics, cytopathology results, TSv3 data, treatment plan, and final histopathology result were reviewed. Results: A total of 50 ITNs underwent TSv3 testing; molecular analysis yielded 20 (40%) "positive" results and 24 (48%) "negative" results. Six (12%) results were classified as "currently negative" or "negative but limited." "Currently negative" results indicate a low-risk mutation that alone is insufficient for development of a malignant lesion. "Negative but limited" results indicate a sample that is nondiagnostic for malignancy due to low cell count. BCR was calculated as ("negative" and "currently negative")/total, resulting in a BCR of 58%. Twenty-three (46%) patients were scheduled for surgery and 27 (54%) patients continued with surveillance. Ninety-one percent (20 of 22) of the resected target nodules were malignant on final pathology. Conclusions: TSv3 proved beneficial in classifying ITNs as positive or negative, avoiding surgery in the latter cases. We found a lower reduction rate in surgery and BCR than the previously published studies, which is attributable to the criteria of the McGill algorithm. In the Canadian public health care system, preventing unnecessary surgery represents significant cost savings for the provincial government while also improving patient quality of life.

The infectious thyroid nodule: a case report of mucormycosis associated with ibrutinib therapy.

BACKGROUND: Acute invasive fungal infections of the head and neck secondary to tyrosine kinase inhibitors are rare and potentially life-threatening events. CASE PRESENTATION: We report a case of mucormycosis of the thyroid gland in a patient known for chronic lymphocytic leukemia receiving ibrutinib who presented with a rapidly growing thyroid nodule and dysphonia. An acute invasive fungal infection was identified on a core needle biopsy; mucormycosis was confirmed on culture. The patient was successfully treated with surgical debridement and long-term antifungal therapy. CONCLUSION: Patients on ibrutinib may be at risk of acute invasive fungal infections of the head and neck.

Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases.

We integrated clinical, genomic, and transcriptomic data from 224 primaries and 95 metastases from 289 patients to characterize progression of pancreatic ductal adenocarcinoma (PDAC). Driver gene alterations and mutational and expression-based signatures were preserved, with truncations, inversions, and translocations most conserved. Cell cycle progression (CCP) increased with sequential inactivation of tumor suppressors, yet remained higher in metastases, perhaps driven by cell cycle regulatory gene variants. Half of the cases were hypoxic by expression markers, overlapping with molecular subtypes. Paired tumor heterogeneity showed cancer cell migration by Halstedian progression. Multiple PDACs arising synchronously and metachronously in the same pancreas were actually intra-parenchymal metastases, not independent primary tumors. Established clinical co-variates dominated survival analyses, although CCP and hypoxia may inform clinical practice.

Treatment of Keloid Scars with Botulinum Toxin Type A versus Triamcinolone in an Athymic Nude Mouse Model.

BACKGROUND: Keloid scarring is a serious condition that mostly affects patients of African or Asian descent. Often disfiguring, this condition can have devastating psychosocial consequences. To date, no treatment modality has been proven ideal. The authors' objectives were (1) to determine the efficacy of botulin toxin type A injection for the treatment of keloid scars compared to steroid injection and to control saline injection (this was achieved through a basic science animal model using athymic nude mice and implanted human keloid tissue); and (2) to analyze the histopathologic changes that occur in an organized keloid scar following botulinum toxin type A injection as compared to steroid and saline injections. METHODS: Keloid scars from four patients were excised and implanted subcutaneously into 28 mice. Three small keloid tissue samples were implanted in each of the 28 mice. One week after implantation, each implant received one of three injections: botulinum toxin type A (treatment drug), saline (control), or steroid injection (first-line gold standard). The keloid tissue was extracted 3 weeks after implantation. Weight analysis, immunohistochemistry, and standard hematoxylin and eosin pathologic analysis were performed on each extracted tissue sample. RESULTS: Paired t test analysis of pretreatment and posttreatment tissue weights revealed a statistically significant difference between the treatment and control groups (p < 0.05). Analysis by a blinded pathologist confirmed fewer collagen bundles in the treatment group. Immunohistochemistry with Ki-67, a marker of cell proliferation, revealed significantly less staining in the treatment groups. CONCLUSION: Botulinum toxin type A could be an effective treatment for keloid scars.

Implementing The Paris System for Reporting Urinary Cytology results in a decrease in the rate of the "atypical" category and an increase in its prediction of subsequent high-grade urothelial carcinoma.

BACKGROUND: In the current study, the authors evaluated the impact of implementing The Paris System for Reporting Urinary Cytology (PSRUC) on the prevalence of various cytological categories and their association with a subsequent diagnosis of high-grade urothelial carcinoma (HGUC). METHODS: A comparative study was conducted over the 6-month period before PSRUC implementation (2013), including 1653 patients and 2371 specimens versus a 6-month period after implementation of the PSRUC (2016), including 1478 patients and 2392 specimens. The following cytological categories were correlated with the subsequent biopsy result when available (355 cases): negative for HGUC (NHGUC), atypical urothelial cells (AUC), suspicious for HGUC, and HGUC. RESULTS: Although 18.6% of specimens were diagnosed as AUC in 2013, the percentage was 14.4% in 2016 (P < .0001). Concurrently, the prevalence of the "benign" category increased from 2013 to 2016 (75.4% vs 80%; P < .0001). After implementation of the PSRUC, there was no significant change noted with regard to the association between the categories of NHGUC, suspicious for HGUC, and HGUC and a subsequent HGUC biopsy diagnosis. However, the predictive value of an AUC diagnosis increased from 28.3% to 46.1% (P = .077). Most important, after the implementation of the PSRUC, there was a significant difference noted with regard to the predictive association for HGUC between the NHGUC and AUC groups (13.6% vs 46.1%; P = .003), a difference that was not found to be statistically significant before implementation of the PSRUC (18% vs 28.3%; P = .175). CONCLUSIONS: There was a much higher risk of HGUC conveyed by AUC cytology after implementation of the PSRUC, justifying more aggressive investigations of patients who receive an AUC diagnosis. Cancer Cytopathol 2018;126:207-14. © 2017 American Cancer Society.

Impact of Implementing the Paris System for Reporting Urine Cytology in the Performance of Urine Cytology: A Correlative Study of 124 Cases.

OBJECTIVES: We assessed the performance of urine cytology using the Paris System for Reporting Urine Cytology (PSRUC) in comparison to our current system. METHODS: In total, 124 specimens with histologic correlation were reviewed and assigned to the PSRUC categories: benign, atypical urothelial cells (AUCs), suspicious for high-grade urothelial carcinoma (SHGUC), and high-grade urothelial carcinoma (HGUC). Original cytological diagnoses were recorded. RESULTS: Fewer cases were given an AUC diagnosis using the PSRUC in comparison to the original diagnoses (26% vs 39%), while the association of AUCs with subsequent HGUC increased from 33% to 53% with the PSRUC. Using the PSRUC resulted in a higher number of low-grade carcinomas assigned to the benign (40%) rather than the AUC (22%) category. The performance of SHGUC/HGUC diagnoses was similar in both systems (predictive value = 94%). CONCLUSIONS: The PSRUC seems to improve the performance of urine cytology by limiting the AUC category to cases that are more strongly associated with HGUC.

Completion thyroidectomy: predicting bilateral disease.

INTRODUCTION: It is not uncommon for patients with indeterminate thyroid nodules to undergo diagnostic hemithyroidectomy. When the final pathology determines that the nodule is in fact malignant, patients require counseling as to the whether a completion thyroidectomy is necessary. OBJECTIVES: 1. Determine the incidence of well differentiated thyroid cancer (WDTC) in the contralateral thyroid lobe in patients undergoing completion thyroidectomy. 2. Identify features of the malignant tumor in the initial resection that increase the likelihood of malignancy in the contralateral lobe. METHODS: Retrospective chart review of 97 patients who underwent hemithyroidectomy and completion thyroidectomy in a university's teaching hospital network between 2006 and 2012. Pathology reports from both surgeries as well as patient and thyroid nodule characteristics were reviewed. RESULTS: Of the 97 patients, 47 (48%) had a malignancy in the contralateral lobe. In the contralateral lobe, 42/47 (89%) of malignancies were papillary microcarcinomas (PMC) and 15/42 (36%) of the PMC were multifocal. Multifocal malignancies in the initial specimen had a 60% rate of contralateral malignancy and were found to be a predictor of bilateral disease (p = 0.04) with OR = 2.74 (95% CI: 1.11-6.79; p = 0.003) in WDTC and OR = 3.59 (95% CI:1.35 9.48; p = 0.01) in papillary cancer specifically. There was no statistical significant correlation established for the following variables: presence of positive cervical nodes, extrathyroidal extension, positive resection margins, size and angio-lymphatic invasion. Moreover, there was no statistical correlation between any of the variants of papillary thyroid cancer and bilateral disease, even though most aggressive subtypes were found to be bilateral. CONCLUSION: In this study, the rate of malignancy in the contralateral lobe was 48%. Multifocality and presence of an aggressive subtype of papillary thyroid cancer in the initial specimen were found to be more important variables to consider in decision-making regarding completion thyroidectomy than size of the initial tumor alone.

Urine cytology: does the number of atypical urothelial cells matter? A qualitative and quantitative study of 112 cases.

INTRODUCTION: This study presents a detailed and systematic morphological and quantitative analysis of urine cytology specimens in order to determine which qualitative and quantitative features are mostly associated with high-grade urothelial carcinoma (HGUCA). MATERIAL AND METHODS: This study included 112 urine cytology cases with a surgical follow-up within 1 year that were originally reported as "atypical," "suspicious for HGUCA," or "positive for HGUCA." The morphological characteristics as well as the number of abnormal cells were correlated with a diagnosis of HGUCA on follow-up biopsy. RESULTS: Multivariate analysis showed that the presence of hyperchromatic atypical cells with nuclear-cytoplasmic ratio ≥ 0.7 was an independent predictor of HGUCA. Similarly, irregular nuclear membranes, single cells, and pleomorphism correlated with surgical outcome whereas eccentric nuclear location, prominent nucleoli, nuclear-cytoplasmic ratio between 0.5 and 0.7 did not. Cases with ≤10 atypical cells had significantly lower rates of subsequent HGUCA than did those with >10 atypical cells (58% versus 77%). Cases with ≤5 atypical cells (n = 26) showed similar prediction rates (58%) for HGUCA than did those with 6 to 10 atypical cells (n = 12). CONCLUSIONS: The number of atypical urothelial cells is an important criterion that should be taken into account when assigning cases to the "positive" or the "suspicious" categories. A preliminary cutoff of 10 cells appears to be easily applicable and valid from the clinical standpoint.

Sentinel Lymph Node Biopsy Status Correlates with Postoperative Stimulated Thyroglobulin Levels in Low-risk Papillary Thyroid Cancer Patients.

OBJECTIVE: Radioactive iodine (RAI) remnant ablation in low-risk papillary thyroid cancer (PTC) is controversial. Current patient selection guidelines recommend the use of postoperative stimulated thyroglobulin (stim-Tg), neck dissections, and sonography but fail to include sentinel lymph node biopsy (SLNB). The objective of this study was to evaluate the correlation between SLNB status and postoperative stimulated thyroglobulin as a surrogate marker of clinical outcome. METHODS: Retrospective chart review of low-risk PTC patients who underwent a total thyroidectomy with SLNB at the McGill Thyroid Cancer Center. SLNBs were obtained using methylene blue dye. Biochemical measurements were acquired between 4 and 12 weeks postoperatively. Statistical analyses were performed using logistic regression models and receiver operating characterisitc (ROC) curves. A P-value <.05 was considered significant. RESULTS: Ninety-six patients were included in this study. The positive SLNB rate was 14.6%. The mean postoperative Tg level was 1.41 µg/L. There were no significant correlations between the SLNB and the covariates analyzed (age, gender, histology, tumor size, and thyrotropin levels). Patients with negative SLNB were significantly more likely to have a lower stim-Tg (P<.0001). When postoperative Tg was analyzed as a categorical variable, a threshold of <1 µg/L was significantly associated with a negative SLNB, with a sensitivity and specificity (determined by ROC curves) of 0.86 and 0.88, respectively. CONCLUSION: There exists a correlation between SLNB and postoperative Tg. This creates the possibility of a new approach to RAI administration among low-risk PTC patients incorporating SLNB to the current guidelines.

Inflammatory myofibroblastic tumor of the larynx-a case report.

OBJECTIVES: Inflammatory myofibroblastic tumor (IMT) is a borderline neoplasm with uncertain malignant potential. It is a rare disease also referred to as an inflammatory pseudotumor, a plasma cell granuloma, and an inflammatory fibrosarcoma. IMT rarely also involves the head and neck region with only 50 cases of laryngeal IMT reported in the literature, and this is the first case with reported magnetic resonance imaging (MRI) findings. METHODS: A 37-year-old man with a 1-year history of hoarseness, dysphagia, and fatigue presented with a right vocal fold submucosal mass and was treated conservatively. RESULTS: The MRI of the neck revealed a mildly spontaneously hyperintense right true vocal fold on GRE images and relative hyperintensity on fat-saturation T2-weighted images. A biopsy of the right-sided submucosal laryngeal mass was performed and the pathologic examination revealed a lesion consistent with an IMT. CONCLUSION: IMT is a borderline neoplasm with uncertain malignant potential. There are many variants of IMT and its etiology is not truly understood. In general, IMT of the larynx has a benign clinical course with low rates of recurrence.

Ectomesenchymal chondromyxoid tumour of the posterior tongue.

Ectomesenchymal chondromyxoid tumor (ECMT) is a rare benign neoplasm arising in the tongue. With only 45 cases reported in the literature, there are several unique features defining this lesion. Firstly, almost all patients present with an asymptomatic slow growing mass on the anterior dorsum of the tongue. At the microscopic level, it is recognizable as a well-circumscribed unencapsulated proliferation of uniform round to fusiform cells embedded in a chondromyxoid matrix. Lastly, the immunohistochemistry profile is characterised by positivity for glial fibrillary acidic protein and frequent positivity for S-100 and cytokeratins. We report a case of a mass located on the posterior dorsum of the tongue and meeting the aforementioned morphological and immunohistochemical criteria of ECMT.

Frozen section analysis and sentinel lymph node biopsy in well differentiated thyroid cancer.

BACKGROUND: The aim of this study is to prospectively review the role of sentinel lymph node (SLN) biopsy in the management of well differentiated thyroid carcinoma (WDTC), and to determine the efficacy of intraoperative frozen section analysis at detecting SLN metastasis and central compartment involvement. METHODS: The SLN biopsy protocol using 1% methylene blue was performed in 300 patients undergoing thyroidectomy for WDTC. A limited pretracheal central compartment neck dissection (CCND) was performed on all patients. Lymph nodes staining blue were considered as SLN's. Both frozen and permanent section analyses were performed. RESULTS: SLN's with metastasis were found in 14.3% (43/300) of cases. Of this, 11% (33/300) were positive on intraoperative frozen section analysis. Frozen section results failed in predicting central compartment involvement in 15 cases (5%) whereas central neck compartment involvement was missed in 5 cases (1.7%) when based on permanent section results. On frozen section analysis, the sensitivity, specificity, positive predictive value and negative predictive value (95% CI) of our SLN biopsy technique aiming to remove all disease from the central compartment was 68.8% (53.6-80.9), 100% (98.1-100), 100% (87.0-100) and 94.4% (90.7-96.7) respectively with P < 0.0001. On permanent section analysis, the values were 89.6% (76.6-96.1), 100% (98.1-100), 100% (89.8-100), and 98.1% (95.3-99.3) with P < 0.0001. CONCLUSION: This data series demonstrates that patients with WDTC have positive SLN's in 14.3% of cases. Moreover, when the SLN's are negative for metastasis on frozen section, the central compartment was disease-free in 94.4% of cases. Finally, this study shows that 23.3% of positive SLN's were false negatives on intraoperative frozen section. According to this data, SLN involvement is an accurate predictor of central compartment metastasis, however surgeons should use caution when relying on intraoperative frozen section to determine whether to perform a CCND.

Vitamin D deficiency as a potentially modifiable risk factor for thyroid cancer.

BACKGROUND: Vitamin D, classically involved in calcium homeostasis, has garnered recent interest for its potential role in cancer prevention and therapy. Although few risk factors have been established in the development of well-differentiated thyroid carcinoma, some would argue that no clear modifiable risk factor exists. Our study is one of the first to explore the relationship between vitamin D deficiency and thyroid cancer. METHODS: This retrospective cohort study was done at a university-affiliated thyroid cancer centre. In 2010, 212 patients undergoing thyroidectomy had their preoperative 25-hydroxyvitamin D(3) levels recorded in addition to the final pathologies of their resected thyroid nodule. The patients were stratified based on vitamin D status; vitamin D deficiency (VDD), reflecting levels under the established threshold of 37.5 nmol/L; and vitamin D sufficiency (VDS), reflecting levels above it. The primary outcome of malignancy rate was used to compare the proportion of malignant nodules in the VDD versus the VDS groups. RESULTS: The malignancy rate rises when comparing the VDS and VDD groups, from 37.5 (33 of 88) to 75% (9 of 12), respectively, corresponding to a relative risk of 2.0 (p  =  .03, 95% CI 1.07-2.66). CONCLUSION: This is the first study to demonstrate the inverse relationship between VDD and well-differentiated thyroid carcinoma. Larger prospective studies are needed to replicate these results. Should this happen, VDD may be the first modifiable risk factor for thyroid cancer.