Efficacy and safety of an artificial dermal graft for the reconstruction of exenterated sockets: a preliminary report.

PURPOSE: The purpose of this study is to report our experience with the use of artificial dermis grafts for orbital socket reconstruction following orbital exenteration (OE). METHOD: A retrospective study was conducted in our ocular oncology centre from May 2018 to June 2020 in patients undergoing OE for orbital malignancies in whom an artificial dermis device (Integra® template, 2 layers) was used for reconstruction. Data recorded included demographics, previous and adjuvant treatments, aetiologies, surgical procedure, surgical reconstruction, complications and follow-up. The main outcome measure was the time between OE and the full granulation of the cavity. RESULTS: Ten patients (mean age, 71.3 years [43-92]) were included. Tumours originated from the conjunctiva (n = 5, 50%), eyelid (n = 3, 30%) and orbit (n = 2, 20%). Nine patients underwent total OE, and one required enlarged OE. Orbital reconstruction was performed using an artificial dermis alone (n = 9, 90%) or combined with regional flaps (n = 1, 10%). The mean granulation time was 3.3 weeks (2-4). Three (30%) patients received adjuvant radiotherapy 1 month post-surgery. The mean time to spontaneous epithelialization was 9.4 weeks (6-12). Preoperative and postoperative radiotherapy was not associated with a delayed epithelialization of the socket (p = 0.463 and p = 0.236, respectively). One (10%) and 2 (20%) patients experienced postoperative socket infection and an ethmoidal fistula, respectively. The mean follow-up was 11.6 months (6-16). CONCLUSION: Using artificial dermis grafts alone or with regional flaps appears to be a viable surgical procedure for orbital socket reconstruction. They reduce surgical morbidity and hospital stay. Preoperative and postoperative radiotherapy does not seem to delay socket healing.

[Does orbital exenteration still has a place in 2019?] / L'exentération orbitaire a-t-elle encore sa place en 2019 ?

INTRODUCTION: Orbital exenteration is a radical anatomically and psychologically disfiguring procedure. It is mostly performed for management of orbital cancers or cancers with orbital involvement. The lack of benefit in terms of overall survival and the development of new molecular therapies (targeted therapies, immunotherapy) in recent years leads us to question its use. The goal of our review is to answer to the following question: is orbital exenteration a viable procedure in 2019? MATERIALS AND METHODS: A literature review was performed using the PUBMED and MEDLINE databases. The following terms were used then crossed with each other: "orbital exenteration", "exenterated socket", "overall survival", "life expectancy", "orbital reconstruction", "socket reconstruction". Oncology articles from the past 15 years were included and separated into those in the oculoplastic literature and those in the ENT literature. RESULTS: Nineteen articles were included in this review. Eyelid tumours represent the main etiology of orbital exenteration. Basal cell carcinoma is the most frequently incriminated tumor, while sebaceous carcinoma and conjunctival squamous cell carcinoma are the most frequently encountered in Asian series. Non-conservative orbital exenteration is the most prevalent surgery performed. Orbital reconstruction depends on the surgeon's speciality: healing by secondary intention and split thickness skin grafts are mostly performed by oculoplastic surgeons, whereas regional or free flaps are mostly performed by ENT surgeons. Cerebrospinal fluid leakage is the most common intraoperative complication, encountered in 0 to 13 % of cases. The most common postoperative complications are ethmoid fistula and infection of the operative site, encountered in 0 to 50 % and 0 to 43 % of cases respectively. Orbital exenteration allows surgical resection of R0 tumors in 42.5 % to 97 % of cases. Overall survival following orbital exenteration is 83 % (50.5-97) and 65 % (37-92) at 1 and 5 years respectively. Identified risk factors for poor overall survival are: age, tumor histology (worse prognosis with choroidal melanoma, better prognosis with basal cell carcinoma), non-R0 surgical resection, locally advanced tumors (size>20mm, BCVA<20/400 and the presence of metastases at diagnosis). Recent studies have demonstrated favorable outcomes when managing locally advanced basal cell carcinoma, lacrimal gland cancer and conjunctival melanoma with targeted therapies or immunotherapies without performing orbital exenteration. CONCLUSION: Orbital exenteration remains a major part of our therapeutic arsenal. Although orbital exenteration has failed to demonstrate any overall survival benefit, it allows satisfactory local control of the disease with an increasingly less invasive procedure. The development of targeted therapies and immunotherapies may change our therapeutic decisions in the future.

Role of supracricoid partial laryngectomy with cricohyoidoepiglottopexy in glottic carcinoma with anterior commissure involvement.

OBJECTIVES: To analyze oncologic and functional outcomes after supracricoid laryngectomy with cricohyoidoepiglottopexy (SCL-CHEP) in glottic carcinoma with anterior commissure (AC) involvement, to determine predictive factors, and to compare results with those reported for other therapeutic strategies. MATERIAL AND METHODS: A retrospective analysis included all patients who underwent SCL-CHEP for glottic squamous cell carcinoma with anterior commissure involvement in our institution, between 2000 and 2014. Swallowing function was evaluated on the DOSS (Dysphagia Outcomes and Severity Scale). RESULTS: Fifty-three patients were included. Three-year overall, cause-specific and recurrence-free survival rates were 86, 95 and 80%, respectively. There were 5 cases of local recurrence (9%), all treated by total laryngectomy. Smoking was the only predictive factor of recurrence-free survival (P=0.02). Mean DOSS score was 5.5±0.9. DOSS scores≥6 (normal oral feeding) were recovered by 59% of patients. T-stage≥2 was the only predictive factor for DOSS score (P=0.04). CONCLUSION: In glottic carcinoma with anterior commissure involvement, SCL with CHEP provided a local control rate of more than 90%, which is higher than reported with endoscopic surgery or external radiotherapy. However, contrary to LSC, salvage of local recurrence can often be obtained by conservative treatments after endoscopic surgery. Therefore, total-laryngectomy-free survival rates after SCL-CHEP and endoscopic surgery are finally comparable.

[Reirradiation of head and neck cancers]. / Réirradiation des cancers des voies aérodigestives supérieures.

Locoregional relapse in previously irradiated region for head and neck tumours is associated with a bad locoregional and distant prognosis. Reirradiation might be exclusive, or feasible in addition with surgery and/or chemotherapy, according to histopronostic factors. Data show that reirradiation is feasible with some severe toxicity due to the bad prognosis of this situation. Hyperfractionnated regimen with split course or normofractionnated regimen without split course are possible with similar efficacy. If tumour size is small, stereotactic ablative radiotherapy may be considered, and if the treatment centre has proton therapy, it could be proposed because of better organs at risk sparing. There is no standard regarding reirradiation schedules and several trials have to be done in order to determine the best technique. Nevertheless, it is agreed that a total dose of 60Gy (2Gy per fraction) is needed. Other trials testing the association with new systemic agents have to be performed, among them agents targeting the PD1/PD-L1 axis.

Candidate apoptotic and DNA repair gene approach confirms involvement of ERCC1, ERCC5, TP53 and MDM2 in radiation-induced toxicity in head and neck cancer.

INTRODUCTION: Single nucleotide polymorphisms (SNPs) of DNA repair and apoptosis genes have been associated with outcome in head and neck squamous cell carcinoma (HNSCC) patients receiving radiotherapy (RT). Our goal was to conduct a candidate gene study in HNSCC patients receiving RT or chemoRT. METHODS: 122 non-resectable HNSCC patients undergoing RT (N=38) or chemoRT (N=84) between 1992 and 2006 were retrospectively analyzed. ERCC1 Lys259Thr (rs735482), ERCC2 Lys751Gln (rs13181), ERCC5 His46His C>T (rs1047768), XRCC1 Arg399Gln (rs25487), TP53 Arg72Pro (rs1042522) and MDM2 309T>G (rs2279744) were analyzed on tumor DNA. SNP profile was considered to assess RT-related toxicity. RESULTS: All 120 evaluable patients experienced RT-related toxicity at any time. Among them, 83% had G3-4 acute side-effects during RT, mainly dysphagia, mucositis, epithelitis and/or xerostomia (DMEX). 28/105 patients (27%) had early G3-4 toxicity up to 3months after the end of RT. 29/96 patients (30%) had G3-4 late toxicity thereafter. The presence of G allele of MDM2 or Thr allele of ERCC1 was associated with a significantly higher risk of acute and/or early DMEX toxicity. The MDM2 309GG genotype was linked to a higher risk of acute G3-4 dermatitis. The ERCC5 TT genotype was associated with more frequent G3-4 late cervical skin fibrosis or xerostomia. Pro allele of TP53 72 was associated with a higher risk of G3-4 osteoradionecrosis. CONCLUSION: Relevant SNPs in DNA repair (ERCC1 and ERCC5) and apoptosis (MDM2 and TP53) genes might influence the severity of radiation-related side-effects in HNSCC patients. Prospective clinical SNP-based validation studies are needed on these bases.

Primary total laryngectomy and pharyngolaryngectomy in T4 pharyngolaryngeal cancers: Oncologic and functional results and prognostic factors.

OBJECTIVES: The aims of this study were to assess oncologic and functional outcome in primary total laryngectomy or pharyngolaryngectomy (TL/TL/TPL) for laryngeal or hypopharyngeal cancer with extra-laryngeal extension (T4) and to determine the predictive factors of these results. MATERIAL AND METHODS: A retrospective analysis was performed on the computerized medical records of all patients undergoing primary TL/TPL for T4 larynx or hypopharynx squamous cell carcinoma between 2000 and 2014 at our institution. Predictive factors of oncologic and functional outcome were investigated on univariate and multivariate analysis. RESULTS: Sixty-three patients (58 men, 5 women; mean age, 68.8±9.7 years) were included. Overall and disease-specific survivals were 69% and 80% at 3 years, and 56% and 69% at 5 years, respectively. On multivariate analysis, gender (female, P<0.001), ASA score (ASA≥3; P=0.006) and vascular embolism (P=0.006) had significant pejorative impact on overall survival. Six months after end of treatment, 90% of patients had recovered independent oral feeding and 83% of those with tracheoesophageal voice prostheses had recovered an intelligible voice. CONCLUSION: Primary TL/TPL remains the gold standard treatment for T4 larynx or hypopharynx cancer. It provides satisfactory oncologic and functional outcomes.

Transoral-transcervical oropharyngectomy without mandibulotomy, associated to fasciocutaneous radial forearm free-flap reconstruction, for oropharyngeal cancer: Postoperative course, oncologic and functional results, and prognostic factors.

OBJECTIVE: To analyze postoperative course, oncologic and functional results and prognostic factors of transoral-transcervical oropharyngeal cancer surgery without mandibulotomy, associated to radial forearm free-flap reconstruction. MATERIAL AND METHODS: Retrospective analysis of computerized medical records of all patients who underwent this type of surgery in our institution between 2004 and 2014. Predictive factors of oncologic and functional results were investigated on univariate and multivariate analyses. RESULTS: Forty-four patients (37 male, 7 female; mean age, 62.3±9.3years) were included. Three-year overall, disease-specific and recurrence-free survival was 90%, 92% and 79%, respectively. Functional scores were satisfactory (normal or slight impairment) for feeding, speech and oral opening functions in 86%, 93% and 100% of cases, respectively. ASA score≥III had significantly negative impact on overall survival (P=0.005) and on feeding (P=0.01) and speech (P=0.01). CONCLUSION: Transoral-transcervical oropharyngeal cancer surgery without mandibulotomy provided excellent oncologic and functional outcomes; it is an advantageous alternative to the conventional conservative transmandibular oropharyngectomy.

Review of sentinel node procedure in cN0 head and neck squamous cell carcinomas. Guidelines from the French evaluation cooperative subgroup of GETTEC.

The reliability of the sentinel lymph node (SN) technique has been established for more than ten years in T1-T2 oral cavity and oropharynx squamous cell carcinoma. Although most authors stress the necessity of rigorous implementation, there are no agreed guidelines. Moreover, other indications have been described, in other anatomical areas of the upper aerodigestive tract and in case of previous surgery or radiotherapy. SN expert teams, under the GETTEC head and neck tumor study group, conducted a review of the key points for implementation in head and neck cancers through guidelines and a review of classical and extended indications. Reliability depends on respecting key points of preoperative landmarking by lymphoscintigraphy, and intraoperative SN sampling and histological analysis. The SN technique is the best means of diagnosing occult lymph node involvement, whatever the primary tumor location, T stage or patient history.

Virtual planning and guided surgery in fibular free-flap mandibular reconstruction: A 29-case series.

INTRODUCTION: Virtual planning and guided surgery (VPGS) has been recently developed for mandibular reconstruction, but benefit remains to be assessed. The aim of this study was to analyze the impact of VPGS on operative time and postoperative course. MATERIAL AND METHODS: All patients who underwent fibula free-flap mandibular reconstruction between 2013 and 2014 in our institution were included in a retrospective study. Operative times and postoperative course were compared between patients who underwent conventional surgery in 2013 and those who underwent VPGS in 2014. RESULTS: A total of 29 patients were included: 11 in 2013 and 18 in 2014. Taking all types of mandibular defect together, ischemia time was significantly decreased by VPGS (75min, vs 150min for conventional surgery; P<0.001), whereas overall operative time was not significantly reduced (481 and 516min, respectively; P=0.4). VPGS had no impact on postoperative course: local or general complications, time to decannulation and nasogastric tube removal, or length of stay. CONCLUSION: VPGS significantly reduced fibula free-flap ischemia time. Long-term functional and esthetic benefit remains to be evaluated.

Head and neck adenoid cystic carcinoma: A prospective multicenter REFCOR study of 95 cases.

OBJECTIVES: To describe the clinical, histological and therapeutic characteristics of a prospective multicenter series of 95 head and neck adenoid cystic carcinoma patients, and to determine any prognostic factors for disease-free survival. PATIENTS AND METHODS: Ninety-five patients with adenoid cystic carcinoma were included in the Réseau d'Expertise Français Des Cancers ORL Rares (REFCOR, French Rare Head and Neck Cancer Expert Network) database between 2009 and 2012. The primary site was the salivary glands in 39 cases, sinus cavities (including hard palate) in 36 cases, pharynx-larynx-trachea in 14 cases, and lips and oral cavity in 4 cases. The tumor was stage I in 15% of cases, stage II in 23%, stage III in 26% and stage IV in 36%. Nine patients had cervical lymph node involvement and 5 had metastases at diagnosis. Fifty-six percent of patients were managed by surgery with postoperative radiation therapy. During follow-up, 3 patients died, 9 developed metastases and 12 showed recurrence or local progression. RESULTS: Mean follow-up was 18 months. On univariate analysis, disease-free survival correlated with T stage (P=0.05), N stage (P=0.003), resection margins (P=0.04), lymph node involvement on histology (P=0.01), and absence of chemotherapy (P=0.03). On multivariate analysis, disease-free survival correlated with T stage (P=0.01), N stage (P=0.09) and surgery (P=0.005). CONCLUSION: The essential issue in adenoid cystic carcinoma is long-term control. The present results confirm that the reference attitude is radical surgical resection for optimal local control. Adjuvant radiation therapy did not emerge as a prognostic factor. This study also provides a starting-point for translational studies in pathology and genetics.

Why and how immunohistochemistry should now be used to screen for the BRAFV600E status in metastatic melanoma? The experience of a single institution (LCEP, Nice, France).

BACKGROUND: Knowledge of the BRAFV600E status is mandatory in metastatic melanoma patients (MMP). Molecular biology is currently the gold standard method for status assessment. OBJECTIVES: We assessed and compared the specificity, sensibility, cost-effectiveness and turnaround time (TAT) of immunohistochemistry (IHC) and molecular biology for detection of the BRAFV600E mutation in 188 MMP. METHODS: IHC, with the VE1 antibody, and pyrosequencing analysis were performed with formalin fixed paraffin embedded tumour samples. RESULTS: The BRAFV600E mutation was detected by pyrosequencing in 91/188 (48%) patients. IHC was strongly positive (3+) in all of these 91 cases. IHC was strongly positive in 9/188 (5%) cases in which the molecular testing failed due to non-amplifiable DNA. Weak or moderate staining was noted in 10/188 (5%) cases in which the molecular biology identified BRAF wild-type tumours. The ratio of the global cost for IHC/molecular biology testing was 1 : 2.2. The average TAT was 48 h vs. 96 h, for IHC vs. molecular biology testing, respectively. CONCLUSIONS: This study showed that VE1 IHC should be a substitute for molecular biology in the initial assessment of the BRAFV600E status in MPP. This methodology needs to be set up in pathology laboratories in accordance with quality control/quality assurance accreditation procedures. Under these strict conditions the question is to know if BRAFV600E-IHC can serve not only as a prescreening tool, but also as a stand-alone test (at least in cases displaying an unequivocally staining pattern) as well as an alternative predictive test for samples for which the molecular biology failed.

[Ectopic thyroid basi-lingual: A case report].

Introduction: The thyroid ectopic gland is a rare anomaly, especially when it's a lingual thyroid. It is characterized by aspecific clinical presentation, causing a diagnostic problem. The diagnosis is based on a combination of imaging techniques as well as histological examination. Case presentation: We are presenting a case of a patient with thyroid basi-lingual treated surgically. Discussion: The low incidence of ectopic lingual thyroid , and their clinical variability requires radiological and isotopic investigations. Conclusion: The diagnosis of this disease is primarily histological. The management of these ectopic thyroid is surgical.

[Cervical lymph nodes: surgeon's point of view]. / Ganglions cervicaux : point de vue du chirurgien.

Squamous cell carcinomas of the upper aerodigestive tract or head and neck cancers, are localized in a complex anatomical region with a major lymphohilic locoregional cervical extension. Cervical lymph node surgery is systematized and drainage areas are sectorized with an increasingly conservative attitude. Improving imaging techniques allow the realization of selective neck dissection; sentinel node techniques are being evaluated. The traditional dissection is reserved to the lymph in capsular rupture or cervical interstitial mass.

[Free flap reconstruction after oral and oropharyngeal advanced stage carcinoma surgery]. / Reconstruction par lambeau libre après chirurgie des cancers de la cavité buccale et de l'oropharynx de stade avancé.

INTRODUCTION: The aim of the study was to evaluate the survival and locoregional recurrence in patients with advanced oral and oropharyngeal squamous cell carcinoma treated by surgery with free flap reconstruction followed or not by radiochemotherapy. POPULATION AND METHODS: A retrospective study was performed on 188 patients treated by surgery with microvascular reconstruction with or without postoperative radiochemotherapy for an advanced stage squamous carcinoma of the oral cavity and/or of the oropharynx. All patients underwent free flap reconstruction. The study parameters were survival and recurrence rates. RESULTS: The 5-year overall survival, disease specific survival, and disease free survival rates were 54%, 65%, and 61% respectively. A high level of comorbidity was the only factor that influenced the survival rate. The overall recurrence rate was 34%. Only 9% of patients having recurred were treated successfully. The survival rate after locoregional recurrence and metastasis was 6% at 2 years. DISCUSSION: Surgery and postoperative radiochemotherapy allows for an acceptable survival rate for patients with advanced oral and oropharyngeal squamous cell carcinoma.

Impact of preoperative radiotherapy on head and neck free flap reconstruction: a report on 429 cases.

BACKGROUND: The primary objective of this study was to evaluate the impact of preoperative radiotherapy on the outcomes of head and neck microvascular reconstruction. The secondary objective was to assess the specific effects of irradiation doses (IDs) ≥60 Gy on the outcomes of head and neck microvascular reconstruction. METHODS: All patients who underwent head and neck free-flap reconstruction in our institution between 2000 and 2010 were included in this retrospective study. A total of 429 patients were enrolled including 136 patients previously irradiated on the head and neck. The impact of preoperative radiotherapy on free-flap success, local and general complications, postoperative mortality, time of decannulation, duration of enteral nutrition and length of stay was assessed in univariate and multivariate analyses. RESULTS: In multivariate analysis, preoperative radiotherapy (irrespective of ID) was a significant risk factor for fistula formation (p = 0.003) and wound infection (p = 0.005). Previous neck irradiation at doses ≥60 Gy was associated with an increased risk of free-flap failure (p = 0.04), overall local complications (p = 0.05), haematoma (p = 0.04) and longer duration of enteral nutrition (p = 0.006) and hospital stay (p = 0.004). CONCLUSIONS: Preoperative radiotherapy, particularly for ID ≥ 60 Gy, is one of the main determinants of the outcomes of head and neck microvascular reconstruction.

Clinical and histological prognostic factors in locally advanced oral cavity cancers treated with primary surgery.

OBJECTIVE: The primary objective of this study was to determine the clinical and pathological prognostic factors in locally advanced oral cavity cancers treated by primary surgery. METHODS: All patients treated by primary surgery with free-flap reconstruction for locally advanced oral cavity squamous cell carcinoma in our institution between 2000 and 2010 were included in this retrospective study. Overall, cause-specific and locoregional disease-free survivals were determined by Kaplan-Meier analyses. Clinical and histological prognostic factors were assessed by univariate (Log Rank tests) and multivariate (Cox models) analyses. RESULTS: A total of 149 patients (102 men and 47 women; mean age=61.3±12.1 years) were included in the study. Five-year overall, cause-specific and locoregional disease-free survivals were 55%, 68% and 71%, respectively. Age, comorbidity and tumour size (histological evaluation) were significantly correlated with overall survival (P<0.05). Age, tumour size, bone invasion and surgical margins were significantly correlated with locoregional disease-free survival (P<0.05). CONCLUSION: The main prognostic factors identified in this study were clinical (age and comorbidity) and histological (pathological tumour size, bone invasion and surgical margins).