A prospective cohort study to assess the role of FDG-PET in differentiating benign and malignant follicular neoplasms.

BACKGROUND: Follicular and Hürthle cell neoplasms are diagnostic challenges. This prospective study was designed to evaluate the efficacy of [18F]-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) in predicting the risk of malignancy in follicular/Hürthle cell neoplasms. MATERIALS AND METHODS: Fifty thyroid nodules showing follicular/Hürthle cell neoplasm on prior ultrasonography guided fine needle aspiration cytology (FNAC) were recruited into this study. A FDG-PET/CT scan, performed for neck and superior mediastinum, was reported by a single observer, blinded to the surgical and pathology findings. Receiver operating characteristic (ROC) curve analysis of maximum standardized uptake value (SUVmax) and the area under the curve (AUROC) were used to assess discrimination between benign from malignant nodules. Youden index was used to identify the optimal cut-off SUVmax for diagnosing malignancy. Sensitivity, specificity, predictive values and overall accuracy were used as measures of performance. RESULTS: Our study group comprises of 31 benign and 19 malignant thyroid nodules. After excluding all Hürthle cell adenomas, the AUROC for discriminating benign and malignant non-Hürthle cell neoplasms was 0.79 (95% CI, 0.64-0.94; p = 0.001); with SUVmax of 3.25 as the best cut-off for the purpose. PET/CT had sensitivity of 79% (95% CI, 54-93%), specificity of 83% (95% CI, 60-94%), positive predictive value (PPV) of 79% (95% CI, 54-93%), and negative predictive value (NPV) of 83% (95% CI, 60-94%). The overall accuracy was 81%. CONCLUSIONS: FDG-PET/CT can help in differentiating benign and malignant non-Hürthle cell neoplasms. SUVmax of 3.25 was found to be the best for identifying malignant non-Hürthle cell follicular neoplasms.

FDG-PET characteristics of Hürthle cell and follicular adenomas.

OBJECTIVE: Follicular (FN) and Hürthle cell neoplasms (HCN) are considered indeterminate on thyroid fine needle aspiration cytology and are preoperative diagnostic challenges. The role of [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) in characterizing indeterminate thyroid nodules remains equivocal, because of the increased FDG uptake by some benign thyroid nodules. The objective of this study was to compare the FDG positron emission tomography/computerized tomography (PET/CT) characteristics of follicular (FA) and Hürthle cell adenomas (HCA). METHODS: Twenty-nine patients with 31 thyroid nodules underwent FDG-PET/CT scans of the neck and superior mediastinum for indeterminate FN/HCN, and were later found to have benign adenomas on final histopathology. All scans were reported by a single observer, who was blinded to the surgical and pathology findings. Receiver operating characteristic (ROC) curve analysis of maximum standardized uptake value (SUVmax) and the area under the curve (AUROC) were used to assess discrimination between FA and HCA. Youden index was used to identify the optimal cut-off SUVmax. Sensitivity, specificity, predictive values and overall accuracy were used as measures of performance. RESULTS: The mean age of our study cohort was 60.7 ± 12.6 years and 77 % of the patients were females. Age of the patients (p = 0.48), their gender (p = 0.52), and the size of thyroid nodules (p = 0.79) were similar for FA and HCA. Increased focal FDG uptake was observed in 100 % of HCA and 52 % of FA (p = 0.02). SUVmax of HCA was significantly higher (p < 0.001) than that of FA. SUVmax of 5 was the best cut-off for discrimination between HCA and FA, with AUROC of 0.90 (95 % CI, 0.79-1.00; p = 0.001). With this cut-off, FDG-PET/CT had sensitivity of identifying HCA of 88 % (95 % CI 47-99 %), specificity of 87 % (95 % CI 65-97 %), positive predictive value of 70 % (95 % CI 35-92 %), and negative predictive value of 95 % (95 % CI 74-99 %). The overall accuracy was 87 %. CONCLUSIONS: HCA shows significantly higher focal FDG uptake as compared to FA and should always be considered in the differential diagnosis of FDG-PET positive thyroid nodules.

An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC/UICC Staging System for Well-Differentiated Thyroid Cancer.

BACKGROUND: Age is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions. METHODS: A total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan-Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model. RESULTS: Using age 45 years as a cutoff, 10-year DSS rates for stage I-IV were 99.7%, 97.3%, 96.6%, and 76.3%, respectively. Using age 55 years as a cutoff, 10-year DSS rates for stage I-IV were 99.5%, 94.7%, 94.1%, and 67.6%, respectively. The change resulted in 12% of patients being downstaged, and the downstaged group had a 10-year DSS of 97.6%. The change resulted in an increase in CPE from 0.90 to 0.92. CONCLUSIONS: A change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model. Such a change would be clinically relevant for thousands of patients worldwide by preventing overstaging of patients with low-risk disease while providing a more realistic estimate of prognosis for those who remain high risk.

Stage II differentiated thyroid cancer: A mixed bag.

BACKGROUND AND OBJECTIVES: AJCC-TNM Stage II well-differentiated thyroid cancer (WDTC) comprises T2N0M0 tumors in patients ≥45 years of age or metastatic WDTC in patients younger than 45 years. The objectives of this study were to assess the oncological outcome of stage II WDTC and to compare the oncological outcome of metastatic WDTC in patient younger (stage II) and older (stage IVC) than 45 years. METHODS: This study involved review of clinical presentation and oncological outcome of population cohort of 2,128 consecutive WDTC, diagnosed during 1970-2010 that includes 215 Stage II WDTC and 61 metastatic WDTC. Cox proportional hazard model was used to assess independent impact of prognostic factors on disease-specific survival (DSS) and disease-free survival (DFS) as calculated by Kaplan-Meier method. RESULTS: Metastatic and non-metastatic stage II WDTC had a 15-year DSS of 41.7% and 96.7%, respectively (P < 0.001). Multivariable analysis showed a 52 times higher risk of death in metastatic stage II WDTC and the DSS of metastatic stage II WDTC was not statistically different from that of stage IVC WDTC. CONCLUSION: Metastatic stage II WDTC is very different from non-metastatic stage II WDTC with oncological outcome similar to stage IVC WDTC.

What is the most appropriate intraoperative baseline parathormone? A prospective cohort study.

INTRODUCTION: The time of drawing pre-incision intraoperative parathyroid hormone (ioPTH) is crucial to provide the right baseline for post-excision PTH measurement. The objective of this study was to identify the optimal time and the numbers of baseline PTH samples that best predict excision of all hypercellular parathyroid tissue when compared with 10-min post-excision PTH level. MATERIALS AND METHODS: In this prospective study, two pre-incision (pre-induction and 10-min post-induction) baseline ioPTH samples along with pre- and post-excision ioPTH were collected and analyzed for 352 parathyroidectomies in 341 patients for sporadic primary hyperparathyroidism at a University hospital. Paired Wilcoxan signed rank test was used to compare the pre-incision ioPTH levels and their percent drop to 10-min post-excision levels. Sensitivity, specificity, predictive values and receiver operating characteristic (ROC) curves were used to compare the predictability of the two pre-incision levels. RESULTS: The difference between pre- and post-induction baseline PTH levels was highly significant (p < 0.001). In 4% cases the criterion of post-excision PTH drop of ≥50% was achieved only with the post-induction baseline PTH and not with pre-induction PTH measurement. Using pre-induction baseline, ioPTH had an overall accuracy of 90% whereas ≥50% fall in the post-excision PTH from the post-induction baseline PTH had the accuracy of 94.85%. DISCUSSION: There was a significant difference between pre- and post-induction PTH levels and Miami criteria was met in 95.45% cases with post-induction baseline. CONCLUSIONS: The optimal time for drawing pre-incision baseline PTH sample is at 10 min post-induction of general anesthesia and positioning of patient.

The changing face of thyroid cancer in a population-based cohort.

In North America, the incidence of thyroid cancer is increasing by over 6% per year. We studied the trends and factors influencing thyroid cancer incidence, its clinical presentation, and treatment outcome during 1970-2010 in a population-based cohort of 2306 consecutive thyroid cancers in Canada, that was followed up for a median period of 10.5 years. Disease-specific survival (DSS) and disease-free survival were estimated by the Kaplan-Meier method and the independent influence of various prognostic factors was evaluated by Cox proportional hazard models. Cumulative incidence of deaths resulting from thyroid cancer was calculated by competing risk analysis. A P-value <0.05 was considered to indicate statistical significance. The age standardized incidence of thyroid cancer by direct method increased from 2.52/100,000 (1970) to 9.37/100,000 (2010). Age at diagnosis, gender distribution, tumor size, and initial tumor stage did not change significantly during this period. The proportion of papillary thyroid cancers increased significantly (P < 0.001) from 58% (1970-1980) to 85.9% (2000-2010) while that of anaplastic cancer fell from 5.7% to 2.1% (P < 0.001). Ten-year DSS improved from 85.4% to 95.6%, and was adversely influenced by anaplastic histology (hazard ratio [HR] = 8.7; P < 0.001), male gender (HR = 1.8; P = 0.001), TNM stage IV (HR = 8.4; P = 0.001), incomplete surgical resection (HR = 2.4; P = 0.002), and age at diagnosis (HR = 1.05 per year; P < 0.001). There was a 373% increase in the incidence of thyroid cancer in Manitoba with a marked improvement in the thyroid cancer-specific survival that was independent of changes in patient demographics, tumor stage, or treatment practices, and is largely attributed to the declining proportion of anaplastic thyroid cancers.

Prognostic nomograms to predict oncological outcome of thyroid cancers.

CONTEXT: Thyroid cancers represent a conglomerate of diverse histological types with equally variable prognosis. There is no reliable prognostic model to predict the risks of relapse and death for different types of thyroid cancers. OBJECTIVE: The purpose of this study was to build prognostic nomograms to predict individualized risks of relapse and death of thyroid cancer within 10 years of diagnosis based on patients' prognostic factors. DESIGN: Competing risk subhazard models were used to develop prognostic nomograms based on the information on individual patients in a population-based thyroid cancer cohort followed up for a median period of 126 months. Analyses were conducted using R version 2.13.2. The R packages cmprsk10, Design, and QHScrnomo were used for modeling, developing, and validating the nomograms for prediction of patients' individualized risks of relapse and death of thyroid cancer. SETTING: This study was performed at CancerCare Manitoba, the sole comprehensive cancer center for a population of 1.2 million. PATIENTS: Participants were a population-based cohort of 2306 consecutive thyroid cancers observed in 2296 patients in the province of Manitoba, Canada, during 1970 to 2010. MAIN OUTCOME MEASURES: Outcomes were discrimination (concordance index) and calibration curves of nomograms. RESULTS: Our cohort of 570 men and 1726 women included 2155 (93.4%) differentiated thyroid cancers. On multivariable analysis, patient's age, sex, tumor histology, T, N, and M stages, and clinically or radiologically detectable posttreatment gross residual disease were independent determinants of risk of relapse and/or death. The individualized 10-year risks of relapse and death of thyroid cancer in the nomogram were predicted by the total of the weighted scores of these determinants. The concordance indices for prediction of thyroid cancer-related deaths and relapses were 0.92 and 0.76, respectively. The calibration curves were very close to the diagonals. CONCLUSIONS: We have successfully developed prognostic nomograms for thyroid cancer with excellent discrimination (concordance indices) and calibration.

The age factor in survival of a population cohort of well-differentiated thyroid cancer.

Well-differentiated thyroid carcinoma (WDTC) represents a group of thyroid cancers with excellent prognosis. Age, a well-recognized risk factor for WDTC, has been consistently included in various prognostic scoring systems. An age threshold of 45 years is currently used by the American Joint Cancer Committee-TNM staging system for the risk stratification of patients. This study analyzes the relationship between the patients' age at diagnosis and thyroid cancer-specific survival in a population-based thyroid cancer cohort of 2115 consecutive patients with WDTC, diagnosed during 1970-2010, and evaluates the appropriateness of the currently used age threshold. Oncological outcomes of patients in terms of disease-specific survival (DSS) and disease-free survival (DFS) were calculated by the Kaplan-Meier method, while multivariable analysis was done by the Cox proportional hazard model and proportional hazards regression for sub-distribution of competing risks to assess the independent influence of various prognostic factors. The mean age of the patients was 47.3 years, 76.6% were female and 83.3% had papillary carcinoma. The median follow-up of the cohort was 122.4 months. The DSS and DFS were 95.4 and 92.8% at 10 years and 90.1 and 87.6% at 20 years, respectively. Multivariable analyses confirmed patient's age to be an independent risk factor adversely affecting the DSS but not the DFS. Distant metastasis, incomplete surgical resection, T3/T4 stages, Hürthle cell histology, and male gender were other independent prognostic determinants. The DSS was not independently influenced by age until the age of 55 years. An age threshold of 55 years is better than that of 45 years for risk stratification.

Impact of a regional acute care surgery model on patient access and outcomes.

BACKGROUND: The consolidation of acute care surgery (ACS) services at 3 of 6 hospitals in a Canadian health region sought to alleviate a relative shortage of surgeons able to take emergency call. We examined how this affected patient access and outcomes. METHODS: Using the generalized linear model and statistical process control, we analyzed ACS-related episodes that occurred between 39 months prior to and 17 months after the model's implementation (n = 14,713). RESULTS: Time to surgery increased after the consolidation. Wait times increased primarily for patients presenting at nonreferral hospitals who were likely to require transfer to a referral hospital. Although ACS teams enabled referral hospitals to handle a much higher volume of patients without increasing within-hospital wait times, overall system wait times were lengthened by the growing frequency of patient transfers. Wait times for inpatient admission were difficult to interpret because there was a trend toward admitting patients directly to the ACS service, bypassing the emergency department (ED). For patients who did go through the ED, wait times for inpatient admission increased after the consolidation; however, this trend was cancelled out by the apparently zero waits of patients who bypassed the ED. Regionalization showed no impact on length of stay, readmissions, mortality or complications. CONCLUSION: Consolidation enabled the region to ensure adequate surgical coverage without harming patients. The need to transfer patients who presented at nonreferral hospitals led to longer waits.

CONTEXTE: Le regroupement des services chirurgicaux d'urgence (SCU) dans 3 hôpitaux sur 6 d'une région sanitaire canadienne visait à contrer une relative pénurie de chirurgiens capables d'effectuer les interventions d'urgence. Nous en avons analysé l'impact sur l'accessibilité des services et sur les résultats chez les patients. MÉTHODES: À l'aide du modèle linéaire généralisé et d'un contrôle statistique des procédés, nous avons analysé les cas adressés aux SCU entre 39 mois précédant et 17 mois suivant l'entrée en vigueur du regroupement des services (n = 14 713). RÉSULTANTS: L'intervalle avant l'intervention chirurgicale s'est allongé après le regroupement des services. Les temps d'attente ont principalement augmenté pour les patients qui consultaient dans un hôpital de premier recours d'où ils étaient susceptibles d'être réorientés vers un hôpital de référence. Même si les équipes des SCU ont permis aux hôpitaux de référence de gérer un volume beaucoup plus important de patients sans augmentation du temps d'attente à l'hôpital même, le temps d'attente dans son ensemble s'est prolongé à l'échelle du système en raison de l'accroissement du nombre de transferts. Les temps d'attente pour les hospitalisations ont été difficiles à interpréter parce qu'on avait tendance à admettre les patients directement aux SCU, en contournant les services d'urgences. Pour les patients qui passaient par les urgences, les temps d'attente pour une hospitalisation ont augmenté après le regroupement; toutefois, cette tendance a été compensée par l'attente pour ainsi dire nulle des patients qui contournaient les services d'urgence. La régionalisation n'a exercé aucun impact sur la durée du séjour, les réadmissions, la mortalité ou les complications. CONCLUSIONS: Le regroupement a permis à la région d'assurer une couverture chirurgicale adéquate sans nuire aux patients. La nécessité de réorienter des patients vers les hôpitaux de référence a contribué à prolonger les temps d'attente.

Lateral approach to central compartment of neck.

Revision surgery in central compartment of neck is often a challenge for the head and neck surgical oncologists/endocrine surgeons. This is often required for completion thyroidectomies, central compartment lymph node dissections, and re-exploration for persistent hyperparathyroidism. Scarring in midline due to prior surgery makes midline access to central compartment difficult and increases the risk of injury to recurrent laryngeal nerve and parathyroid glands. This article describes a simple technique of approaching central compartment between sternocleidomastoid and strap muscles.

What is the adequate margin of surgical resection in oral cancer?

OBJECTIVE: The "adequate surgical margin" has always remained an enigma in the minds of head and neck surgeons. This study systematically analyses the impact of the width of the clear surgical margin on survival in oral cancer. STUDY DESIGN: A historical cohort of 277 surgically treated patients with oral cancer were followed for a median period of 36 months. Cox proportional hazard models were used to determine the independent effect of the clear surgical margin, in millimeters, on 5-year survival. RESULTS: Patients with margins of 5 mm or more had a 5-year survival rate of 73% when compared to those with margins of 3 to 4 mm (69%) , 2 mm or less (62%), and involved margins (39%, P = .000). After controlling for confounding variables (age, gender, stage) each 1-mm increase in clear surgical margin decreased the risk of death at 5 years by 8% (HR 0.92; 95% CI 0.86, 0.99; P = .021). Based on this model, patients with positive surgical margins had a 2.5-fold increase in risk of death at 5 years and those with close (

Impact of use of frozen section assessment of operative margins on survival in oral cancer.

OBJECTIVE: This study looked at the independent impact of intraoperative frozen section assessment of the adequacy of margins of excision on disease control and survival. STUDY DESIGN: The design was a review of outcome of historical cohort of 416 surgically treated oral cancer patients at a comprehensive cancer center. Status of the margins at permanent sections, disease failure at the primary site, and survival data of 229 patients who had frozen sections were compared by univariate and multivariate analysis with 197 patients who did not have frozen sections. RESULTS: Failure at the primary site was independently influenced by age at diagnosis (P < .001), T stage (P = .016), N stage (P = .042), and status of margins on paraffin sections (P = .005). Chance of achieving clear margins on paraffin sections was, however, not significantly improved by the use of frozen sections. On multivariate analysis, the use of frozen sections did not independently have an impact on local failure or survival. CONCLUSIONS: Frozen section assessment of mucosal margins has not improved the disease outcome.

Sternocleidomastoid muscle interposition to prevent carotid artery blowout.

Carotid blow-out syndrome is the most dreaded complication in head and neck surgical oncology practice This article describes a simple technique of interposition of sternocleidomastoid muscle between pharynx and carotid sheath to isolate the latter from salivary contamination in the event of salivary leak. Authors have used this technique in 83 laryngectomies with excellent results.

Treatment outcomes in squamous cell carcinoma of the maxillary alveolus and palate: a population-based study.

OBJECTIVE: This population-based historical cohort study evaluates the treatment outcomes of primary squamous cell carcinoma of the maxillary alveolus and hard palate. METHODS: A historical cohort of 37 cases of previously untreated biopsy-proven squamous cell carcinoma of the upper jaw registered in the Province of Manitoba from January 1975 to January 2004 was analyzed. RESULTS: The tumor epicenter involved the maxillary alveolus in 26 patients and the hard palate in 11 patients. The mean age of the study population was 72.8 years and 67% were women with a documented tobacco use rate of 50%. Forty-one percent had stage I or II disease, 51% stage III or IV, and 8% could not be staged. Treatment included radiotherapy as a single modality (13.5%), surgery (38%), surgery and radiotherapy (24%), and palliative treatment (24%). Local recurrence was observed in 10 patients with 6 failing at the primary site. The absolute and disease-free survival at 5 years was 33% and 62% respectively. The 5-year disease-free survival was 82% for stage I and II and 48% for stage III and IV (P = .056). No patient treated with radiotherapy as a single treatment modality survived 5 years. Disease-free survival for patients treated with surgery, and surgery +/- radiotherapy, was 69% and 73% at 5 years, respectively (P = .001). CONCLUSIONS: Squamous cell carcinoma of the maxillary alveolus and palate differs from other oral cancers in that the patients are relatively older with a slight female predilection. Treatment with surgery, with or without radiotherapy, appears to improve disease control.

Population-based study of treatment outcomes in squamous cell carcinoma of the retromolar trigone.

BACKGROUND: Carcinoma of the retromolar trigone is relatively uncommon. High rates of local recurrence account for a relatively poor prognosis. STUDY DESIGN: A population-based historical cohort of 76 cases with biopsy-proven squamous cell carcinoma of the retromolar trigone were studied as a case series. Kaplan-Meier survival curves and log rank test were used for statistical analysis. RESULTS: The mean age was 67.2 years. Fifty-six patients were male, 45% had T1 or T2 tumors, and 61% were staged as N0. Treatment included radiotherapy in 35%, surgery alone in 26%, surgery and radiotherapy in 23%, and 16% received palliative treatment. The absolute and disease-specific survivals at 5 years were 51.4% and 67.7%, respectively. In patients treated with surgery, the resection margin status predicted the overall 5-year survival (P = .027), with 75% of patients with negative margins surviving 5 years versus a survival of 0% of patients with involved margins. CONCLUSIONS: Squamous cell carcinoma of the retromolar trigone has a poor survival rate for early-stage disease. Adequate surgical margins can improve survival.

The clinical significance of the positive surgical margin in oral cancer.

The objective of surgical management of squamous cell carcinoma of the oral cavity is adequate resection with a clear margin. This study examines the significance of the positive surgical margin. An historical cohort of 425 patients from the cancer registry of the Province of Manitoba with squamous cell carcinoma of the oral cavity treated with surgery +/-radiotherapy was examined. A Cox's proportional hazard model was used to examine the independent effect of surgical margins on five-year survival. Seventy-two percent of tumors involved the tongue and floor of mouth, and 43% of patients presented with Stage III and IV disease. The 5-year absolute and disease specific survivals were 62% and 74.5% respectively. Survival was related to age >65 years (P=0.0177), T-Stage (P=0.0002), and N-Stage (P=0.0465). Patients with clear margins had a survival rate of 69% at 5 yrs (median survival >60 mos) compared to 58% with close (median survival >60 mos) and 38% with involved margins (median survival 31 mos, P=.0000). After controlling for significant prognostic factors, involved surgical margins increased the risk of death at 5 years by 90% (HR 1.9, 95% CI 1.2,2.9, P=0.0026). The status of the surgical margin is an important predictor of outcome. The surgical margin, in contrast to the other prognostic indicators, is under the direct control of the surgeon.

Dynamic MR lymphangiography and carbon dye for sentinel lymph node detection: a solution for sentinel lymph node biopsy in mucosal head and neck cancer.

BACKGROUND: The practical application of sentinel lymph node biopsy in squamous cell carcinoma of the head and neck is restricted by the time sensitivity of blue dye and lack of spatial resolution and nonspecific node enhancement with radiocolloid. This study evaluates the use of magnetic resonance (MR) lymphangiography and carbon dye labeling to circumvent these limitations. METHODS: Gadomer/carbon dye mixture was injected into the tongue and stifle of adult swine (n = 4). MR lymphatic mapping was followed by intraoperative mapping with isosulfan blue dye. Sentinel lymph node biopsy and completion node dissection were performed 60 minutes after injection in four nodal basins and at 7 days after injection in eight. RESULTS: The technique was successful in all 12 nodal basins. The sentinel lymph nodes were stained black at the time of the immediate and delayed dissections. CONCLUSIONS: MR lymphangiography provides temporal and anatomic localization of the sentinel lymph node with a single investigation. Carbon dye is a sensitive and persistent visual marker of MRI-targeted sentinel lymph nodes.