[SURGICAL TREATMENT OF LOCALLY ADVANCED WELL DIFFERENTIATED THYROID CARCINOMA].

AIMS: We aimed to better define the most appropriate therapeutic protocol for this type of tumor. BACKGROUND: The incidence of well-differentiated thyroid carcinoma is rising and the mortality from the disease remains low for patients with early disease. Nevertheless, the survival of patients with advanced disease has not improved during the last four decades and a controversy still exists in the literature regarding the optimal treatment in patients with locally advanced (T4) differentiated thyroid carcinoma. METHODS: Meta-analysis of the literature and our institutional experience, in treating patients with advanced papillary/follicular thyroid carcinoma. The main outcome measures were overall survival (OS) and disease-specific survival (DSS). RESULTS: The study group consisted of 38 patients with locally advanced thyroid carcinoma (T4). Regional spread to nodal metastases was present in 25 (65.7%) patients. Tracheal invasion was diagnosed in 29 (76.3%), of those 10 (26.3%) patients had airway obstruction. Recurrent laryngeal nerve (RLN) paralysis was revealed with clinical evidence during diagnosis in 23 (60.5%) patients. The 5-years OS was 66% and DSS was 87%. Multivariate analysis of outcome showed that undifferentiated carcinoma foci and vocal cord paralysis were associated with significantly reduced 5-years OS, and vocal cord paralysis was the only independent prognostic variable for DSS. Male gender and adjuvant radioactive iodine treatment were significant prognostic variables for disease free survival but not OS or DSS. CONCLUSIONS: Surgical resection remains the mainstay of treatment for locally advanced differentiated thyroid cancers. Foci of poorly differentiated cells, vocal cord paralysis and male gender are associated with poor prognosis. Radioactive iodine treatment improved local control but did not not affect OS. These patients should be managed by a multidisciplinary team in university centers specializing in treating complicated cancer patients.

Primary tumor staging for oral cancer and a proposed modification incorporating depth of invasion: an international multicenter retrospective study.

IMPORTANCE: The current American Joint Committee on Cancer (AJCC) staging system for oral cancer demonstrates wide prognostic variability within each primary tumor stage and provides suboptimal staging and prognostic information for some patients. OBJECTIVE: To determine if a modified staging system for oral cancer that integrates depth of invasion (DOI) into the T categories improves prognostic performance compared with the current AJCC T staging. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 3149 patients with oral squamous cell carcinoma treated with curative intent at 11 comprehensive cancer centers worldwide between 1990 and 2011 with surgery ± adjuvant therapy, with a median follow-up of 40 months. MAIN OUTCOMES AND MEASURES: We assessed the impact of DOI on disease-specific and overall survival in multivariable Cox proportional hazard models and investigated for institutional heterogeneity using 2-stage random effects meta-analyses. Candidate staging systems were developed after identification of optimal DOI cutpoints within each AJCC T category using the Akaike information criterion (AIC) and likelihood ratio tests. Staging systems were evaluated using the Harrel concordance index (C-index), AIC, and visual inspection for stratification into distinct prognostic categories, with internal validation using bootstrapping techniques. RESULTS: The mean and median DOI were 12.9 mm and 10.0 mm, respectively. On multivariable analysis, DOI was a significantly associated with disease-specific survival (P < .001), demonstrated no institutional prognostic heterogeneity (I² = 6.3%; P = .38), and resulted in improved model fit compared with T category alone (lower AIC, P < .001). Optimal cutpoints of 5 mm in T1 and 10 mm in T2-4 category disease were used to develop a modified T staging system that was preferred to the AJCC system on the basis of lower AIC, visual inspection of Kaplan-Meier curves, and significant improvement in bootstrapped C-index. CONCLUSIONS AND RELEVANCE: We propose an improved oral cancer T staging system based on incorporation of DOI that should be considered in future versions of the AJCC staging system after external validation.

Minimum nodal yield in oral squamous cell carcinoma: defining the standard of care in a multicenter international pooled validation study.

PURPOSE: There is evidence to suggest that a nodal yield <18 is an independent prognostic factor in patients with clinically node negative (cN0) oral squamous cell carcinoma (SCC) treated with elective neck dissection (END). We sought to evaluate this hypothesis with external validation and to investigate for heterogeneity between institutions. PATIENTS AND METHODS: We analyzed pooled individual data from 1,567 patients treated at nine comprehensive cancer centers worldwide between 1970 and 2011. Nodal yield was assessed with Cox proportional hazard models, stratified by study center, and adjusted for age, sex, pathological T and N stage, margin status, extracapsular nodal spread, time period of primary treatment, and adjuvant therapy. Two-stage random-effects meta-analyses were used to investigate for heterogeneity between institutions. RESULTS: In multivariable analyses of patients undergoing selective neck dissection, nodal yield <18 was associated with reduced overall survival [hazard ratio (HR) 1.69; 95 % confidence interval (CI) 1.22-2.34; p = 0.002] and disease-specific survival (HR 1.88; 95 % CI 1.21-2.91; p = 0.005), and increased risk of locoregional recurrence (HR 1.53; 95 % CI 1.04-2.26; p = 0.032). Despite significant differences between institutions in terms of patient clinicopathological factors, nodal yield, and outcomes, random-effects meta-analysis demonstrated no evidence of heterogeneity between centers in regards to the impact of nodal yield on disease-specific survival (p = 0.663; I (2) statistic = 0). CONCLUSION: Our data confirm that nodal yield is a robust independent prognostic factor in patients undergoing END for cN0 oral SCC, and may be applied irrespective of the underlying patient population and treating institution. A minimum adequate lymphadenectomy in this setting should include at least 18 nodes.

Laser-induced hyperthermia for treatment of granulation tissue growth in rats.

OBJECTIVE: We aimed to develop a new technique for treatment of granulation tissue (GT) growth using local hyperthermia. METHODS: A temperature-controlled diode laser system was developed for induction of mild hyperthermia in real time. GT was generated by harvesting the skin over the gluteal fascia in rats. Histopathological analysis was used to estimate the effect of hyperthermia on the tissue. RESULTS: In untreated rats, GT was detected within 3 days and reached maximal thickness after 12 days. Hyperthermia at 43 degrees C and above significantly decreased GT thickness (n = 8 per group). Hyperthermia at 48 degrees C for 3 minutes was the most efficient parameter for treatment of GT (51% reduction), with minimal (5%) muscle necrosis. CONCLUSIONS: Hyperthermia can significantly inhibit GT growth, with minimal damage to surrounding structures. Our findings suggest a possible role for hyperthermia as a therapeutic model against GT. Further research and long-term studies are needed to explore the utility of laser-induced hyperthermia for inhibition of GT growth.