Tranexamic acid in head and neck procedures: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: We conducted a meta-analysis of all randomized controlled trials (RCTs) that examined the benefits of tranexamic acid (TXA) among cancer patients undergoing head and neck (H&N) procedures. METHODS: We screened five databases from inception until 20 June 2021 and evaluated the risk of bias of the eligible studies. We pooled continuous outcomes using the weighted mean difference (WMD) with 95% confidence interval (CI). RESULTS: Five studies, comprising seven RCTs, met the inclusion criteria. This meta-analysis included a total of 540 patients; 265 and 275 patients were assigned to the TXA and control group, respectively. Overall, the included RCTs revealed a low risk of bias. The volume of postoperative bleeding was significantly lower in favor of the TXA group compared with the control group (n = 7 RCTs, WMD = - 51.33 ml, 95% CI [- 101.47 to - 1.2], p = 0.04). However, no significant difference was found between both groups regarding the volume of intraoperative bleeding (n = 6 RCTs, WMD = - 3.48 ml, 95% CI [- 17.11 to 10.15], p = 0.62), postoperative hemoglobin (n = 3 RCTs, WMD = 0.42 mg/dl, 95% CI [- 0.27 to 1.11], p = 0.23), duration of drainage tube removal (n = 4 RCTs, MD = - 0.41 days, 95% CI [- 1.14 to 0.32], p = 0.27), and operation time (n = 6 RCTs, WMD = 1.59 min, 95% CI [- 10.09 to 13.27], p = 0.79). TXA was safe and did not culminate in thromboembolic events or major coagulation derangements. CONCLUSION: TXA administration is safe and significantly reduces the volume of postoperative bleeding. However, no difference is identified between TXA and control groups regarding the volume of intraoperative bleeding, postoperative hemoglobin level, duration of drainage tube removal, and operation time.

Risk for Thyroid Cancer Recurrence Is Higher in Men Than in Women Independent of Disease Stage at Presentation.

Background: Well-differentiated thyroid cancer (DTC) presents at a more advanced stage in men than in women, and the mortality in men is higher than that in women. However, it is not clear whether DTC recurrence is affected by sex independent of stage at presentation. The objective of the present study was to assess if male sex is an independent risk factor for recurrence of DTC. Methods: The Canadian Collaborative Network for Cancer of the Thyroid (CANNECT) is a collaborative registry to describe patterns of care for thyroid cancer. We included patients from the CANNECT registry with DTC diagnosed at age 18 or older between 2000 and 2010. We compared men and women with respect to presentation, management, and recurrence risk, stratified for American Joint Committee on Cancer (AJCC) stage. Results: We included 2595 patients, 2067 (79.7%) women and 528 (20.3%) men. Men presented with more advanced AJCC stage (p < 0.001), T stage (p < 0.001), N stage (p < 0.001), and M stage (p = 0.002) There was no difference in follow-up duration between women (7.7 ± 4.0 [mean ± standard deviation] years) and men (7.7 ± 4.0 years, p = 0.985). Overall recurrence was 2.2% (n = 46) for women and 8.5% (n = 45) for men (p < 0.001). In multivariate analysis adjusted for AJCC stage, men were at significantly greater risk for DTC recurrence than women (adjusted hazard ratio 2.72 [95% confidence interval [CI] 1.78-4.20]; p < 0.001). In multivariate analysis adjusted for tumor-node-metastasis (TNM) stage, men were at significantly greater risk for DTC recurrence than women (adjusted hazard ratio 2.31 [CI 1.48-3.60]; p < 0.001). Conclusions: Our study confirms that the risk for recurrence of DTC is higher in men than in women. Although men tend to present with more advanced-stage disease, the difference in recurrence risk persists when adjusted for stage of presentation. It needs to be determined whether sex should influence follow-up intensity and/or duration.

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.

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.

Transient early increase in thyroglobulin levels post-radioiodine ablation in patients with differentiated thyroid cancer.

OBJECTIVES: Treatment of differentiated thyroid cancer (DTC) includes surgical thyroidectomy and, in most cases, radioactive iodine (RAI) ablation. Measurement of serum thyroglobulin (Tg) levels is used for assessing disease burden and identifying persistent-recurrent DTC. This prospective study determined the Tg profile before and after RAI-ablation in patients with DTC. DESIGN AND METHODS: Fifty-five DTC patients with complete resection received RAI-ablation and were assessed for Tg at baseline (non-stimulated), pre-ablation (stimulated), 7 days post-ablation (stimulated) and at 6 months (stimulated). Stimulation of Tg was achieved by thyroid hormone withdrawal to achieve serum thyroid stimulating hormone (TSH) ≥30 mU/L. Thyroid remnant size was estimated from whole body scintigraphy. Similar protocols were implemented for nine patients with incomplete resection/metastatic disease for comparison. RESULTS: Mean stimulated Tg levels for DTC patients with complete resection at 7 days post-RAI increased 13-fold from 13.7 to 175.5 µg/L (p<0.0001), and the Tg levels reduced to 2.3 µg/L (p<0.0001 versus post-RAI) by follow-up. None of the patients had recurrence of disease. For the nine patients with incomplete resection/metastases, Tg levels were higher throughout compared to the patients with complete resection. There was no increase in Tg between pre- and post-RAI. We did not observe a significant correlation between the remnant size and Tg increase. CONCLUSIONS: This study confirms a prominent transient early increase in Tg post-RAI ablation in DTC patients with complete resection, with the Tg levels falling below baseline by 6 months. This is presumed to reflect RAI-induced thyroid tissue destruction/inflammation with subsequent release of Tg from the thyroid remnant. Recognizing this transient phenomenon is important for post-ablation Tg interpretation and patient management.

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.

Clinicopathological and prognostic implications of genetic alterations in oral cancers.

This study evaluated the clinicopathological and prognostic implications of genetic alterations characterizing oral squamous cell carcinoma(OSCC). Comparative genomic hybridization(CGH) was used to identify chromosomal alterations present in primary OSCCs obtained from 97 pateints. In this population, tobacco use was a significant risk factor for OSCC. By contrast, all 97 of our samples are negative for human papillomavirus (HPV) DNA integration, which is another known risk factor for OSCC in certain populations. Results of the Fisher's exact test followed by Benjamini-Hochberg correction for multiple testing, showed a correlation of 7p gain and 8p loss with node-positive OSCC (p≤0.04 for both genetic alterations) and association of 11q13 gain with high-grade OSCC (p≤0.05). Univariate Cox-proportional hazard models, also corrected for multiple testing, showed significant association of 11q13 gain and 18q loss with decreased survival (p≤0.05). These findings were supported by multivariate analysis which revealed that 11q13 gain and 18q loss together serve as a strong bivariate predictor of poor prognosis. In conclusion, our study has identified genetic alterations that correlate significantly with nodal status, grade, and poor survival status of OSCC. These potential biomarkers may aid the current TNM system for better prediction of clinical outcome.

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.

Marginal mandibulectomy: 11 years of institutional experience.

PURPOSE: Literature on marginal mandibulectomy deals mainly with floor of mouth cancers. The purpose of the present study was to evaluate the oncologic outcome of marginal mandibulectomy in buccal sulcus cancer as compared with floor of mouth cancer. PATIENTS AND METHODS: Chart review of 179 patients who underwent marginal mandibulectomy during 1993 to 2003 at Tata Memorial Hospital yielded 161 marginal mandibulectomies done for squamous cell carcinoma (SCC). Oncologic outcomes in terms of disease control and cause-specific survival for the gingival buccal and tongue/floor of mouth cancers were compared. Independent impact of various prognostic factors on the local control and cause-specific survival was evaluated using Cox proportional hazards model. RESULTS: A total of 137 marginal mandibulectomies were done for SCC in gingival buccal complex and 24 for floor of mouth SCC. Bone was microscopically involved in 13 (8.1%) cases and mucosal margin of excision showed tumor in 12 (7.5%) cases. However, they had no influence on locoregional failure or cause-specific survival. Cause-specific survival at 2 and 5 years was 85.6% and 72.2%, respectively. Cause-specific survival at 5 years was significantly better for buccal cancer than floor of mouth cancer (P = .041). On multivariate analysis patients with floor of mouth cancer were at a 3 times higher risk of dying of disease than those with buccal cancer. CONCLUSION: In carefully selected patients, marginal mandibulectomy in buccal sulcus cancer achieves at least as good local control and survival as compared with the floor of mouth cancer.

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.

Tumor antigens eliciting autoantibody response in cancer of gingivo-buccal complex.

Cancer of the gingivo-buccal complex (GBC) is a major cancer in Indian men. This study reports the identification of tumor antigens, which elicit an antibody response in cancer of GBC using immunoproteomics. Proteins from KB cells separated by 2-D PAGE, were immunoblotted with IgG from sera of 28 cancer patients, 12 patients with leukoplakia, and 28 healthy individuals. Antigens detected by the IgGs from the patient's sera were different among different individuals with presence of any single antigen ranging from 7 to 79%. Several of these antigens have been identified by MS and confirmed by immunostaining. They are three forms of α-enolase, peroxiredoxin-VI, annexin-II, HSP70, pyruvate kinase, α-tubulin, ß-tubulin, ATP-synthase, phosphoglycerate mutase (PGM), aldose reductase, triosephosphate isomerase, and cyclophilin-A. Except, HSP70, these antigens are being reported in cancer of GBC for the first time. Pyruvate kinase and aldose reductase have not been reported to elicit autoantibody response in any other cancer earlier. Initial results show that autoantibody response against α-enolase, HSP70, annexin-II, peroxiredoxin-VI, and aldose reductase are also seen in patients with leukoplakia of GBC, which suggest early occurrence of these autoantibodies during the process of oral carcinogenesis. These antigens can be further validated for their use in cancer management by immune intervention.