Multifocal recurrence on the transaxillary robotic thyroidectomy incision.

INTRODUCTION: Robotic thyroidectomy (RT) has been reported to achieve satisfactory results. However, its long-term oncological results have not been validated. The use of RT to treat thyroid cancer comprises specific risks that are not encountered with open thyroidectomy (OT). CASE SUMMARY: We report the case of a patient operated by two-stage RT for stage pT3a follicular carcinoma, followed by tumour seeding along the incision despite adjuvant Iodine-131 therapy and external beam radiotherapy. DISCUSSION: This case illustrates the limitations and insufficient perspective of RT for thyroid cancer, with the recent discovery of a risk of tumour seeding along the incision. Rigorous patient selection should help to avoid this risk of tumour seeding.

An exploratory, open-label, randomized, multicenter study to investigate the pharmacodynamics of a glycoengineered antibody (imgatuzumab) and cetuximab in patients with operable head and neck squamous cell carcinoma.

BACKGROUND: In addition to inhibiting epidermal growth factor receptor (EGFR) signaling, anti-EGFR antibodies of the IgG1 'subtype' can induce a complementary therapeutic effect through the induction of antibody-dependent cell-mediated cytotoxicity (ADCC). Glycoengineering of therapeutic antibodies increases the affinity for the Fc-gamma receptor, thereby enhancing ADCC. PATIENTS AND METHODS: We investigated the changes in immune effector cells and EGFR pathway biomarkers in 44 patients with operable, advanced stage head and neck squamous cell carcinoma treated with two preoperative doses of either glycoengineered imgatuzumab (GA201; 700 or 1400 mg) or cetuximab (standard dosing) in a neoadjuvant setting with paired pre- and post-treatment tumor biopsies. RESULTS: Significant antitumor activity was observed with both antibodies after just two infusions. Metabolic responses were seen in 23 (59.0%) patients overall. One imgatuzumab-treated patient (700 mg) achieved a 'pathological' complete response. An immediate and sustained decrease in peripheral natural killer cells was consistently observed with the first imgatuzumab infusion but not with cetuximab. The functionality of the remaining peripheral natural killer cells was maintained. Similarly, a pronounced increase in circulating cytokines was seen following the first infusion of imgatuzumab but not cetuximab. Overall, tumor-infiltrating CD3+ cell counts increased following treatment with both antibodies. A significant increase from baseline in CD3+/perforin+ cytotoxic T cells occurred only in the 700-mg imgatuzumab group (median 95% increase, P < 0.05). The most prominent decrease of EGFR-expressing cells was recorded after treatment with imgatuzumab (700 mg, -34.6%; 1400 mg, -41.8%). The post-treatment inflammatory tumor microenvironment was strongly related to baseline tumor-infiltrating immune cell density, and baseline levels of EGFR and pERK in tumor cells most strongly predicted therapeutic response. CONCLUSIONS: These pharmacodynamic observations and relationship with efficacy are consistent with the proposed mode of action of imgatuzumab combining efficient EGFR pathway inhibition with ADCC-related immune antitumor effects. CLINICAL TRIAL REGISTRATION NUMBER: NCT01046266 (ClinicalTrials.gov).

[Postoperative external beam radiotherapy for medullary thyroid carcinoma with high risk of locoregional relapse]. / Radiothérapie postopératoire des carcinomes médullaires de la thyroïde à haut risque de rechute locorégionale.

PURPOSE: To assess the outcome of locally advanced medullary thyroid carcinoma treated with surgery and adjuvant external beam radiotherapy. PATIENTS AND METHODS: Twenty-nine consecutive patients with non-metastatic medullary thyroid carcinoma treated in our institution between January 1995 and December 2012 were retrospectively evaluated. All underwent curative-intended optimal surgery, followed by external beam radiotherapy because of high risk of locoregional relapse. Twelve patients were stage III, 16 IVa and 1 IVb. Positive surgical margins were present in 11 cases (10 R1 and 1 R2). Median and average preradiotherapy serum calcitonin were 141pg/mL and 699pg/mL, respectively. Fourteen patients received 3D-conformal radiotherapy and 15 received intensity-modulated radiotherapy. Median prescribed dose was 63Gy to the high-risk volumes and 54Gy to the low-risk volumes. Treatment was delivered in 30 fractions. The median gap between surgery and radiotherapy was 1.9months. Median follow-up was 76.4months. RESULTS: Kaplan-Meier estimates of 5-year locoregional relapse-free survival and overall survival were 79 and 96 %, respectively. Among the five locoregional relapses, two were related to a macroscopic metastatic cervical lymph node that was unfortunately not removed during the lymphadenectomy. Eight of ten patients with microscopic positive margins (R1) were controlled regarding the thyroidectomy bed. Eight patients had normal serum calcitonin after external beam radiotherapy, of whom only one developed a locoregional relapse during follow-up. Regarding the 21 patients with persistent positive serum calcitonin after treatment, only ten developed a macroscopic locoregional or distant relapse. One grade III and no grade IV acute morbidity were reported. Fifteen patients reported grade II chronic morbidity and no grade III/IV. CONCLUSION: Maximal surgery followed by adjuvant external beam radiotherapy as a treatment for locally advanced medullary thyroid carcinoma provides a high rate of long-term locoregional control and overall survival with limited toxicity. Postoperative external beam radiotherapy should be considered when patients present features indicating a high risk of locoregional relapse.

[Value of neck dissection before definitive radiation therapy for locoregionally advanced squamous cell carcinoma of the head and neck]. / Place du curage ganglionnaire avant radiothérapie exclusive dans la prise en charge des carcinomes épidermoïdes localement évolués des voies aérodigestives supérieures.

PURPOSE: Optimal timing of neck dissection remains debated in the conservative management of patients with locoregionally advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: The files of 63 patients with radiographic evidence of bulky or necrotic nodal metastases treated by up-front neck dissection and definitive radiotherapy between 2000 and 2012 at two institutions were retrospectively reviewed. RESULTS: The primary site was oropharyngeal, hypopharyngeal or laryngeal in 63%, 21% and 13% cases, respectively. Overall, 83% of the tumours were staged pN2b or more. Extracapsular spread was found in 48 cases (77%). After a 48-month median follow-up, the 3-year locoregional control and overall survival were 88% and 68%, respectively. Only one isolated failure occurred in the dissected neck. CONCLUSION: This combination therapy provides a good locoregional tumour control. It should be considered as an option in laryngeal, hypopharyngeal or oropharyngeal squamous cell carcinomas with bulky or necrotic nodal metastases at presentation.

Osteosarcomas of the mandible: multidisciplinary management of a rare tumor of the young adult a cooperative study of the GSF-GETO, Rare Cancer Network, GETTEC/REFCOR and SFCE.

BACKGROUND: Mandibular osteosarcomas (MOS) mostly affect young adults. Their treatment is extrapolated from that of extragnathic osteosarcomas. MATERIAL AND METHODS: A retrospective multicooperative group study was conducted to determine the impact of chemotherapy, adjuvant radiation therapy and surgery on outcomes and to identify prognostic factors. This ethical committee-approved study included a centralized review of histology slides and operative reports. RESULTS: Of 111 patients, 58.6% were male, median age 35 years (13%, ≤18 years). Histology was osteoblastic, chondroblastic, fibroblastic, conventional not otherwise specified and others in 39.6%, 30.6%, 8.1%, 12.6% and 8.0%, respectively. Pathological World Health Organisation grades were low, intermediate and high grade in 6.4%, 11.8% and 81.8%, respectively. Surgery was carried out for 94.5% of patients. Neoadjuvant chemotherapy (mixed protocols) was carried out in 93.1% of patients. Postoperative chemotherapy and radiotherapy were carried out in 54.7% and 23.8%, respectively. Median follow-up was 59.6 months (range). Five-year local control, metastasis-free, disease-free and overall survival rates were 64.6%, 68.9%, 53.2% and 69.2%, respectively. Survival was significantly associated with age, tumor size and surgery. Wide surgery with clear margins and free flap reconstruction was the strongest prognostic factor. Neoadjuvant chemotherapy improved disease-free and metastatic-free survival and increased clear margins rates from 50% to 68%. Intermediate grades behaved like high grades in terms of metastatic-free and disease-free survival. CONCLUSION: This homogeneous series is the largest to date and emphasizes the major impact of clear margins and multidisciplinary management. Neoadjuvant chemotherapy improves disease-free survival and should be recommended for both high and intermediate grade MOS.

Lymph node management in clinically node-negative patients with papillary thyroid carcinoma.

AIMS: Systematic lymph node dissection in patients with papillary thyroid carcinoma (PTC) remains controversial. The objective of this study was to study the pattern of lymph node spread in patients with PTC clinically node-negative and then to propose a lymph node management strategy. METHODS: We retrospectively reviewed the records of patients who had undergone total thyroidectomy and a systematic central neck dissection (CND) and lateral neck dissection. Ninety patients with PTC without lymph nodes metastases (LNM) detected on preoperative palpation and ultrasonographic examination were included. RESULTS: Forty-one patients (45.5%) had LNM. Twenty-eight patients (31%) had a central and a lateral involvement. Thirteen patients (14.5%) had only a central involvement. All the patients without LNM in the central compartment were also free in the lateral compartment. There was no correlation between LNM status and TNM staging. The largest LNM in the central compartment was smaller than or equal to 5mm in 66% of the cases, and that could explain the lack of sensitivity of the preoperative ultrasonographic examination. CONCLUSION: CND could be considered at preoperative or intraoperative diagnosis of PTC whereas lateral neck dissection should be performed only in patients with preoperative suspected and/or intraoperatively proven LNM. Systematic CND allows an objective evaluation of lymph node status in this central cervical area where the LNM are particularly small and difficult to detect preoperatively.

[Systematic neck dissection in squamous cell carcinoma of the oral cavity]. / Evidement cervical systématique dans les cancers épidermoïdes de la cavité orale.

OBJECTIVES: To evaluate the neck control after prior surgical management of patients with squamous cell carcinoma of the oral cavity and to quantify the ratio of patients among whom neck dissection did not have a real therapeutic value. To discuss the usefulness of the sentinel node biopsy in this group of patients. METHOD: Retrospective analysis of patients with epidermoid carcinoma of the oral cavity who had systematically a neck dissection. RESULTS: Thirty-nine files of patients have been processed. We found 45% patients classified pN0 (among whom about one half where classified pT4). With a mean follow-up of 19 months, we did not find any cervical lymph node relapse. Five patients died (13.5%) without any cervical disease. CONCLUSION: The systematic cervical lymph node dissection remains the most effective means to obtain the neck control of squamous cell cancers of the oral cavity. It however was applied without therapeutic value for 45% of the patients of this series. The validation of the sentinel node concept as a method of cervical staging should make it possible to avoid this surgical procedure in more than one third of the cases.

Modification of the infra hyoid musculo-cutaneous flap.

BACKGROUND: In 1986, Wang described the infra hyoid musculo-cutaneous flap. Here, we report technical adaptations and improvements to this flap. METHODS: From 1994 to 1996, we performed 61 infrahyoid flaps using the classical procedure. After 5 years of technical evolution, we studied a new series of 91 flaps from January 2000 to June 2002. We reviewed our experience with the infra hyoid flap and described the surgical procedure, its evolution and the impact on the viability of the flap. RESULTS: In the two series, the main arterial pedicle was usually the superior thyroid artery. Venous drainage was more variable; consequently we always performed a modified neck dissection with preservation of the internal jugular vein. In the first series, the surgical results were good with only seven local complications essentially skin necrosis. The functional and aesthetic results seemed acceptable. In the second series, the results, after technical evolution with better venous drainage and cervical closure, were improved (only one necrosis) and the indications were extended. CONCLUSION: With experience, the infra hyoid myocutaneous flaps is reliable and appears as a particularly useful flap for oral cavity, oral pharynx and pharyngeolaryngeal reconstruction.

Head and neck squamous cell carcinoma in elderly patients: a long-term retrospective review of 273 cases.

BACKGROUND: The prolongation of life expectancy results in an increasing number of malignant neoplasms occurring in the elderly population. For a long time these patients were not considered good candidates to receive aggressive therapy and probably were inadequately treated in many instances. OBJECTIVE: To assess the outcome of patients older than 74 years who had had head and neck squamous cell carcinoma. MATERIALS AND METHODS: In our database of 4610 consecutive patients with head and neck squamous cell carcinomas who were evaluated and treated at the Centre Oscar Lambret, Northern France Comprehensive Cancer Center, Lille, over a 10-year period (1974-1983), we identified 273 patients who were 75 years or older. The outcome was updated for all patients included in the database. RESULTS: A significantly higher proportion of females were noted in the older patient group (43/273, 15.8%) than in younger patient group (192/4337, 4.4%, P<.001). There were no differences for primary site except for hypopharyngeal squamous cell carcinoma that occurred less frequently in the elderly patients (8.8% vs 14.5%, borderline significance P =.02). There were no differences for TNM stage grouping, histological classification, incidences of previous cancer, and comorbidities. Surgery was performed in a smaller proportion of older patients (13.9% vs 27.4%, P<.001, for the primary site and 15.4% vs 35.6%, P<.001, for those occurring in the neck) as well as chemotherapy that was delivered in 5.5% vs 17.7% (P<.001). On the contrary, there was no difference in radiotherapeutic treatments. Tolerance to treatment was similar and there was the same proportion of persistent diseases 2 months after completion of the overall treatment (27.8% vs 25.4%, P =.94). Pooling local, regional, and distant failures and metachronous cancers, there was a borderline lower incidence in older patients (57.1% vs 64.2%, P =.02), which is explained by an obvious shorter life expectancy. If survival is not meaningful in such a comparison (5-year survival 23.8% vs 36.4%), then the causes of deaths may be compared. Among the 4067 patients who were dead at the last update, index tumor evolution-related deaths numbered 130 (48.1% of dead patients in this cohort) in older patients compared with 2045 (53.9% of dead patients in this cohort), which was not significantly different. There was no difference in treatment-related deaths (11.1% vs 9.3%). Fewer intercurrent disease-related deaths occurred in the older patients (19.7% vs 11.8%). CONCLUSIONS: Head and neck squamous cell carcinoma in elderly patients did not seem to have a significantly different outcome when compared with head and neck squamous cell carcinoma occurring in younger patients. When properly monitored, conventional therapies seem feasible in older patients.

[Anticancer chemotherapy, risk factor for infection at the operated site in cervicofacial surgery]. / Chimiothérapie anti-cancéreuse, facteur de risque d'infections du site opératoire en chirurgie propre cervico-faciale.

BACKGROUND: In order to evaluate occurrence and risk factors for wound infection (WI) in head and neck uncontaminated surgery, we carried out a prospective study. METHODS: From january 1997 through january 1999, we prospectively evaluated 212 wounds of all patients having uncontaminated head and neck surgery at the Oscar Lambret Cancer Center (neck dissections, parotidectomies, thyroidectomies, explorative cervicotomies, cutaneous resections). No antibiotic prophylaxis was given. WI was defined as a wound with pus. Statistical evaluation was performed using the chi 2 test. In univariate analysis, differences were considered significant p < 0.05. RESULTS: The overall WI rate was 6.6% (14/212). In univariate analysis, previous chemotherapy is the only risk factor for WI were: (p < 0.00001). Multivariate analysis was not performed. CONCLUSION: Like other cancer locations, chemotherapy was a major risk factor for WI. In these cases, a phase ill trial could confirm efficacy of standard antibiotic.

Risk factors for wound infection in head and neck cancer surgery: a prospective study.

BACKGROUND: The goal of this prospective study is to determine risk factors for wound infections (WI) for patients with head and neck cancer who underwent surgical procedure with opening of upper aerodigestive tract mucosa. METHODS: One hundred sixty-five consecutive surgical procedures were studied at Oscar Lambret Cancer Center within a 24-month interval. Twenty-five variables were recorded for each patient. Statistical evaluation used Chi2 test analysis (categorical data) and Mann-Whitney test (continuous variables). RESULTS: The overall rate of WI was 41.8%. Univariate analysis indicated that five variables were significantly related to the likelihood of WI: tumor stage (p =.044), previous chemotherapy (p =.008), duration of preoperative hospital stay (p = 022), permanent tracheostomy (p =.00008), and hypopharyngeal and laryngeal cancers (p =.008). CONCLUSIONS: Despite antibiotic prophylaxis, WI occurrence is high. These data inform the head and neck surgeon, when a patient is at risk for WI and may help to design future prospective studies.

[Elements of epidemiology and initiation of carcinogenesis in carcinomas of the upper aerodigestive tract. Future therapeutic consequence?]. / Eléments d'épidémiologie et initiation de la cancérogénèse dans les carcinomes des VADS. Conséquence thérapeutique future?

The study of epidemiology and of the carcinogenesis in epidermoid carcinomas of the upper aerodigestive tract shows that their occurrence is not random. Tobacco abuse plays a major role, especially because of benzopyrene, mutagen of the P53 gene, however it is associated with many other potentiating factors: alcohol, metals, hydrocarbures, virus, food, climate, genetic fragility that create genetic lesions at the origin of carcinogenesis. The latter occurs as "field cancerization" with multiple alterations of the mucosa and general attack of the control systems of the differentiation, growth and cell apoptosis which usually protect the cell against the phenomena of carcinogenesis. The P53 protein gene, retinoid receptors as well as the system of detoxifying glutathion S transferase are modified at the very early stage of these diseases, these abnormalities can be logically related to epidemiological data. These data lead us therefore to imagine complementary specific reverting therapies of induced genetic abnormalities, through the reexpression of non mutated gene encoding P53 protein and the use of retinoid. These various modalities are reported hereafter.

[Current knowledge on the action of retinoids in carcinoma of the head and neck]. / Connaissances actuelles sur l'action des rétinoides dans les carcinomes des VADS.

The retinoids are a pharmacologic class based on the vitamin A or retinol. The most known related derivatives are the all-trans (ATRA), 13 and 9 Cis retinoic acids. The antitumor and differenciative activities have been demonstrated in: in vitro, in vivo and clinical studies. In head and neck cancers, the clinical phase III trials in chemoprevention of second primary tumors have shown discordant results related to the type of retinoic acid. Nuclear retinoic acid receptors are members of the steroid-thyroid and vitamin D3 superfamily of nuclear receptors which regulate differenciation proliferation and apoptosis in cooperation with mediated proteins of the apoptosis (especially p53 protein). A thorough knowledge on the earlier mechanisms involved in carcinogenesis of squamous cell carcinomas would lead to futur reversal therapy with the reversal of pathologic to normal tissues by the restauration of mechanisms of the physiologic control. This futur clinical trial research could provide cancer prevention and control by the induction of cellular differentiation rather than proliferation (retinoids) and/or the expression of tumor-suppressor genes (p53 protein transfection). Finally, the retinoids treatment should be performed in control studies because of the toxicity at high doses.

[Endonasal ethmoidectomy in the treatment of nasal sinus polyposis]. / L'ethmoïdectomie endonasale dans le traitement de la polypose naso-sinusienne.

Endonasal surgery of paranasal polyposis. Two hundred and fifty one microscopical sphenoethmoidectomies with a major complication rate of 2.6% are reported. Long term results are analysed. Nasal obstruction disappears in 96% and persists in 70% of the cases 5 years later. Through topical steroid therapy and surgical experience polyp recurrence rate is reduced to 30%.