Transoral robotic surgery for the treatment of T1-T2 carcinoma of the larynx: preliminary study.

OBJECTIVES/HYPOTHESIS: To determine the feasibility and the preliminary oncological results of transoral robotic surgery (TORS) for the treatment of early stage laryngeal tumors. STUDY DESIGN: Retrospective single center study. METHODS: We reviewed the medical records of 23 patients who underwent TORS for the treatment of T1 or T2 laryngeal squamous cell carcinoma between August 2009 and March 2012. RESULTS: Laryngeal tumors were involving the glottis (13 cases) and the supraglottis (10 cases). They were classified T1 N0 in 16 cases, T2 N0 in four cases, and T2 N+ in three cases. The median TORS operative time was 60 minutes (ranging from 30 to 118 minutes). The median hospitalization time was 7.5 days. Histopathological examination of the resected tumors confirmed 14 cases in which the margins were clear, four cases in which the surgical margins were close (less than 1 mm), one case in which the margins were microscopically positive, and in four cases margins status were not able to be recorded. A tracheostomy was carried out for three patients, and 11 patients got a nasogastric feeding tube postoperatively. The local recurrence rate was 8.7% (2/ 23 cases), and in both cases the recurrence occurred in the anterior commissure area only. The overall larynx preservation rate was 95,7% (22/ 23 cases). CONCLUSION: In this preliminary study, we demonstrated that laryngeal TORS is feasible and may result in oncological results comparable with other treatment strategies, including laser CO2 surgery. This innovative approach needs to be evaluated through randomized multi-institutional trial. LEVEL OF EVIDENCE: 4.

Transaxillary robotic thyroid surgery: a preliminary European experience.

BACKGROUND: Robot-assisted endoscopic transaxillary thyroidectomy is an emerging surgical technique that needs to be evaluated in European patients. We evaluate the feasibility and preliminary results of our experience of this technique in a cohort of patients from within a single European university hospital (Nîmes, France). METHODS: We performed a retrospective review of the first 23 patients, treated consecutively between September 2010 and June 2012. RESULTS: Nine patients underwent total thyroidectomy and 14 patients lobectomies. All procedures were completed successfully with a mean total operative time of 134 min. We observed a single case of internal jugular vein injury during the console time. No instances of persistent complications were observed; however, minor postoperative events occurred in 5 patients. Pathological diagnoses included benign follicular adenoma in 18 patients, benign adenoma with lymphoid thyroiditis in 1 patient, and benign adenoma with Graves' disease in 4 patients. CONCLUSIONS: Robotic thyroid surgery is feasible in European patients and can be safely performed on selected patients. This technique has infrequent minor complications and provides a high level of satisfaction.

Robotic thyroid surgery: our experience with the infraclavicular approach.

BACKGROUND: Robot-assisted endoscopic transaxillary thyroidectomy is an emerging surgical technique. Despite promising results it presents some limitations and remains controversial in terms of usefulness and validity. We developed an alternative robotic technique using a gasless infraclavicular approach. METHODS: We tested this approach using cadaveric dissection, then we performed the technique on a series of 21 patients from October 2009 to July 2010. RESULTS: Sixteen patients underwent total thyroidectomy and 5 patients underwent lobectomies. Mean total operative time was 197 minutes. We observed postoperative complications in 4 patients. Pathologic diagnoses included: benign follicular adenoma (19 patients) and single papillary carcinoma <1 cm in diameter pT1a (2 patients). CONCLUSIONS: The infraclavicular approach for robotic thyroidectomy is feasible, but is not safe enough to be recommended, based on our experience and on the technical difficulties encountered. The use of 2 robotic arms instead of 3 is a major limitation for this technique.

The use of preoperative routine measurement of basal serum thyrocalcitonin in candidates for thyroidectomy due to nodular thyroid disorders: results from 2733 consecutive patients.

CONTEXT: The preoperative routine measurement of basal serum thyrocalcitonin (CT) in candidates for thyroidectomy due to thyroid nodules is currently a subject of debate. OBJECTIVE: The objective of this study was to evaluate the role of systematic basal serum CT measurement in improving the diagnosis and surgical treatment of medullary thyroid carcinoma (MTC) in patients undergoing thyroidectomy for nodular thyroid disorders, regardless of preoperative CT levels. DESIGN: We determined basal serum CT levels in 2733 consecutive patients before thyroid surgery and performed a pentagastrin test in patients with hypercalcitoninemia. We correlated basal and stimulated CT levels with intraoperative and definitive histopathological findings, and we analyzed the impact of these results on surgical procedures. RESULTS: Twelve MTCs were found among the 43 patients with basal serum CT level of 10 pg/ml or greater. Two MTCs were present among the 2690 patients with normal CT levels. MTC was always present in patients with a basal CT of 60 pg/ml or greater. For CT levels ranging from 10 to 59 pg/ml, MTC was diagnosed in 11% of patients. When preoperative hypercalcitoninemia was present, total thyroidectomy associated with comprehensive intraoperative histopathological analysis allowed the intraoperative diagnosis of five latent, subclinical MTCs. The pentagastrin test gave no additional diagnostic information for the management of patients with elevated preoperative basal serum CT level. CONCLUSION: Routine measurement of CT in the preoperative work-up of nodular thyroid disorders is useful. This procedure improves intraoperative diagnosis of MTC and enables adapted initial surgery, the most determinant factor of treatment success.

Gene expression profiling in head and neck squamous cell carcinoma: Clinical perspectives.

BACKGROUND: To date, more than 60 gene expression profiling (GEP) studies have been published in the field of head and neck squamous cell carcinoma (HNSCC) with variable objectives, methods, and results. METHODS: The purpose of this study was to present a state-of-the-art review of GEP in HNSCC focusing on the current advances and perspectives for clinical applications. RESULTS: Gene expression signatures have been developed to identify screening and diagnostic molecular markers, to improve tumor staging (cervical lymph node and distant metastasis prediction), to differentiate lung metastasis of HNSCC from primary lung squamous cell carcinoma, to predict tumor response to chemoradiotherapy, and to provide outcome predictors. CONCLUSION: Some transcriptional signatures that could improve HNSCC management have been identified, but further analyses are required to properly validate and to precisely evaluate their clinical relevance. After an exploratory phase, the completion of large scale projects with stringent methodology is now necessary to transfer GEP from bench to bedside.

Clinical relevance of nine transcriptional molecular markers for the diagnosis of head and neck squamous cell carcinoma in tissue and saliva rinse.

BACKGROUND: Analysis of 23 published transcriptome studies allowed us to identify nine genes displaying frequent alterations in HNSCC (FN1, MMP1, PLAU, SPARC, IL1RN, KRT4, KRT13, MAL, and TGM3). We aimed to independently confirm these dysregulations and to identify potential relationships with clinical data for diagnostic, staging and prognostic purposes either at the tissue level or in saliva rinse. METHODS: For a period of two years, we systematically collected tumor tissue, normal matched mucosa and saliva of patients diagnosed with primary untreated HNSCC. Expression levels of the nine genes of interest were measured by RT-qPCR in tumor and healthy matched mucosa from 46 patients. MMP1 expression level was measured by RT-qPCR in the salivary rinse of 51 HNSCC patients and 18 control cases. RESULTS: Dysregulation of the nine genes was confirmed by the Wilcoxon test. IL1RN, MAL and MMP1 were the most efficient diagnostic markers of HNSCC, with ROC AUC > 0.95 and both sensitivity and specificity above 91%. No clinically relevant correlation was found between gene expression level in tumor and T stage, N stage, tumor grade, global survival or disease-free survival. Our preliminary results suggests that with 100% specificity, MMP1 detection in saliva rinse is potentially useful for non invasive diagnosis of HNSCC of the oral cavity or oropharynx, but technical improvement is needed since sensitivity was only 20%. CONCLUSION: IL1RN, MAL and MMP1 are prospective tumor diagnostic markers for HNSCC. MMP1 overexpression is the most promising marker, and its detection could help identify tumor cells in tissue or saliva.

Reference gene selection for head and neck squamous cell carcinoma gene expression studies.

BACKGROUND: It is no longer adequate to choose reference genes blindly. We present the first study that defines the suitability of 12 reference genes commonly used in cancer studies (ACT, ALAS, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPL27, RPS29, SHAD and TBP) for the normalization of quantitative expression data in the field of head and neck squamous cell carcinoma (HNSCC). RESULTS: Raw expression levels were measured by RT-qPCR in HNSCC and normal matched mucosa of 46 patients. We analyzed the expression stability using geNorm and NormFinder and compared the expression levels between subgroups. In HNSCC and/or normal mucosa, the four best normalization genes were ALAS, GAPDH, RPS18 and SHAD and the most stable combination of two genes was GAPDH-SHAD. We recommend using KALPHA-TBP for the study of T1T2 tumors, RPL27-SHAD for T3T4 tumors, KALPHA-SHAD for N0 tumors, and ALAS-TBP for N+ tumors. ACT, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPS29, SHAD and TBP were slightly misregulated (<1.7-fold) between tumor and normal mucosa but can be used for normalization, depending on the resolution required for the assay. CONCLUSION: In the field of HNSCC, this study will guide researchers in selecting the most appropriate reference genes from among 12 potentially suitable reference genes, depending on the specific setting of their experiments.

Updated definition of level VI lymph node classification in the neck.

CONCLUSION: This update will enable us to precisely address the involvement pattern of level VI and to standardize treatment procedures in order to refine their indications and eventually improve their results and avoid treatment morbidity. BACKGROUND: The neck level classification is being used worldwide to describe the lymph nodes status of the neck. It provides standardized data to properly evaluate and then improve our protocols for the management of neck metastasis in an evidence-based medical manner. Although level VI treatment is challenging in cancer of the larynx, pharynx, trachea, esophagus, and thyroid, our knowledge about its involvement relies on few non-standardized data, due to the inadequate definition of this region. METHOD: We propose an updated radiological and surgical definition of level VI, with the introduction of two sublevels which fulfill surgical, radiotherapy, radiological, and pathological concerns. RESULTS: Level VIa encompasses prelaryngeal, intercricothyroidal, pretracheal, and perithyroidal nodes. Level VIb encompasses inferior laryngeal nodes. Within the traditional limits of level VI, all lymph nodes lying between the inferior border of the hyoid bone and the inferior border of the cricoid cartilage belong to level VIa. Between the inferior border of the cricoid cartilage and the top of the suprasternal notch, lymph nodes lying in front of the posterior face of the thyroid gland belong to level VIa; those lying behind this boundary belong to level VIb. We also discuss the definition of the superior mediastinal lymph nodes, which should not be mistaken for level VI.

Early maturation of evoked otoacoustic emissions and medial olivocochlear reflex in preterm neonates.

The present study was designed to investigate the early maturation of the brainstem regulation of the cochlear function in preterm neonates. Evoked otoacoustic emissions (EOAE) and their regulation via the medial olivocochlear efferent (MOC) reflex were investigated in a large population of preterm neonates and compared with full-term neonates and young babies from birth to 4 y and school-aged children. In 28-wk preterm neonates, EOAE were seen in the mid-frequency range. These responses extended both to the low (down to 1025 Hz) and high (up to 6152 Hz) frequency ranges at 38 wk of gestational age and remained stable up to 4 mo. At this stage, the amplitude of EOAE overlapped adult values. EOAE amplitudes then decreased to reach adult values at 3 y of age. Maturation of MOC efferents innervating the outer hair cells was investigated by studying the suppressive effect of contralateral sound on the EOAE amplitudes (MOC reflex). The first MOC responses were recorded in preterm neonates of 32-33 wk of gestational age, reaching adult-like values at 37 wk of gestational age. The maximum effect of MOC efferent activation occurred between 2000 and 4000 Hz. These results suggest that, in humans, MOC efferents mature in utero. Thus, testing the MOC reflex may have a clinical relevance to detect an abnormal development of the auditory pathways, particularly of a brainstem circuitry not explored through conventional testing.

Contralateral sound stimulation suppresses the compound action potential from the auditory nerve in humans.

BACKGROUND: In the past decade, contralateral sound suppression of otoacoustic emissions has been extensively used to study the role of the medial olivocochlear efferent in humans. In most studies, the suppressive effect of contralateral sound stimulation was not greater than 2 to 4 dB. However, the relation between the degree of otoacoustic emission reduction and the neural auditory threshold is unknown. METHODS: The current study investigates the effect of contralateral sound stimulation by measuring compound action potential response from the auditory nerve during retrosigmoid surgery in humans. RESULTS: Although only a small number of subjects responded to contralateral sound stimulation, we report that efferent activation by contralateral sound stimulation results in 10 dB effective neural attenuation. CONCLUSIONS: Together with previous otoacoustic emission measurements in humans, this result demonstrates that the suppressive effect of contralateral noise suppression is greater when measured with compound action potential than otoacoustic emissions, and that contralateral sound suppressive effect is at least as strong in humans as in animals.