Circulating levels of FoxP3, M2 (sCD163) and IGF-1 as potential biomarkers associated with Laryngeal Squamous Cell Carcinoma in Tunisian patients.

We aim to assess the clinical impact of circulating levels of sCD163, FoxP3, IGF-1 in LSCC patients (Laryngeal Squamous Cell Carcinoma). The concentrations of sCD163, FoxP3, and IGF-1 were measured using ELISA test in the serum samples collected from 70 pretreatment LSCC patients and 70 age and sex-matched healthy controls. Statistical analysis was performed using ANOVA to compare the two groups, and the correlation between markers and clinical parameters. Receiver-Operator Characteristic (ROC) curve analysis was conducted to determine the optimal cutoff values and evaluate the diagnostic impact of these markers. Significant differences in the levels of sCD163, FoxP3, and IGF-1 were observed between LSCC patients and the control group, with respective p-values of 0.01, 0.022, <0.0001. The determined cutoff values for sCD163, FoxP3, IGF-1 concentrations were 314.55 ng/mL, 1.69 ng/mL, and 1.69 ng/mL, respectively. The corresponding area under the curve (AUC) values were 0.67 (95% CI: 0.57-0.76), 0.70 (95% CI: 0.61-0.80), 0.84 (95% CI: 0.76-0.92), respectively. Furthermore, it was found that IGF-1 concentrations exceeding 125.20 ng/mL were positively correlated with lymph node metastasis. Elevated serum levels of sCD163, FoxP3 and IGF-1 are associated with the diagnosis of LSCC. IGF-1 appears to be the most promising indicator for the LSCC progression.

Tracheal Hemangioma: A Rare Cause of Hemoptysis in Children.

Tracheal hemangioma is a very rare benign vascular tumor. Few cases of tracheal hemangioma in children are reported in the literature. Chronic cough is the main symptom of the disease; however, hemoptysis is rarely reported as a symptom of tracheal hemangioma in children. Here, we report a case of tracheal hemangioma in an eight-year-old girl admitted to our pediatric department for recurrent hemoptysis. Routine biological and radiological investigations were normal. Diagnosis was made using computed tomography and bronchoscopy. Beta-blocker therapy was not efficient. Bronchoscopic treatment by electrical excision enables complete recovery. Tracheal hemangioma should be considered a cause of recurrent hemoptysis when routine biological and radiological investigations are negative.

Surgical Approaches to Parapharyngeal Space Tumors: An Example and Review of the Literature.

Parapharyngeal space tumors (PPS) are rare. They represent less than 1% of all head and neck tumors. They are of various histologies. Pleomorphic adenomas originating from the parotid (prestylian parapharyngeal space) are the most frequent. We report the case of a 50-year-old patient treated for a pleomorphic adenoma (PA) of PPS. His initial complaints were apnea and dysphagia. The correct diagnosis was preoperatively suspected by magnetic resonance imaging (MRI). The surgery was carried out using two approaches: transoral and cervical transparotid approaches. Definitive histology was consistent with encapsulated pleomorphic adenoma. In the present work, we reviewed clinical, radiological, and histological features of parapharyngeal space tumors. We tried to summarize the common surgical approaches. The chosen approach is, in fact, scheduled taking into account several parameters including tumor volume and purpose of the surgery.

Petrous metastasis of a lung small cell carcinoma.

Malignant tumors of the temporal bone are rare. They include a wide histological variety. They are mostly primary tumors with an estimated incidence of 0.8-1.0 per 1,000,000 inhabitants per year [1]. Metastases form an uncommon subgroup. The clinical features of these temporal bone metastases are nonspecific and predominantly consist of hearing loss, vertigo, facial palsy, tinnitus, headache, otalgia or otorrhoea [2]. The aim of our publication is to report a rare case of metastasis in the temporal bone as initial manifestation of lung cancer. Our patient was a 44-year-old man who presented for a right mastoid swelling with a grade VI right facial nerve palsy. Imaging and biopsy confirmed the diagnosis of small cell lung carcinoma petrous metastasis. The treatment was palliative. An osteolytic lesion of the temporal bone in an elderly patient may fit with a primary tumor of the temporal bone. It must, also, suggest the diagnosis of metastasis. The malignant tumor most frequently responsible is breast cancer, but lung cancer must also be considered in smoking patients.

The Clinical Significance of IGF-1R and Relationship with Epstein-Barr Virus Markers: LMP1 and EBERs in Tunisian Patients with Nasopharyngeal Carcinoma.

OBJECTIVES: Tunisia is in the endemic area of nasopharyngeal carcinoma. Epstein-Barr virus (EBV) based assays have been commonly used as standard markers for screening and monitoring the disease. So, it is very important to find novel factors for the early diagnostic and prognostic evaluation of this cancer. The aim of the study was to evaluate the expression of IGF-1R (Insulin Growth Factor Receptor 1), LMP 1 (Latent Membrane Protein 1) and EBERs (EBV encoded RNAs) in order to determine their correlation with clinicopathologic parameters and survival rates in patients with nasopharyngeal carcinoma (NPC). We also looked for the relationship between these biomarkers. METHODS: IGF-1R and LMP1 expression was performed by means of immunohistochemical method and EBERs were detected using in situ hybridization of paraffin embedded tumor tissues of 94 patients with nasopharyngeal carcinoma and 45 non-cancerous nasopharyngeal mucosa samples. RESULTS: Our findings demonstrated that IGF-1R was over expressed in 47.87% of NPC patients and only in 2.22% of controls. Positive LMP1 expression was detected in 56.38% of NPC patients and all NPC patients were positive for the EBV-encoded RNAs staining. A statistically significant positive correlation was observed between IGF-1R expression and the tumor size (P < .001). Kaplan-Meier survival curves showed that NPC patients with a strong IGF-1R expression level have shorter median and 5-year Overall Survival than those with weak expression rates (100.15 vs 102.68 months, P = .08). In addition, median and 5-year Disease-Free Survival was significantly lower in the LMP1 positive NPC patients than in the LMP1 negative ones (53.38 vs 93.37 months, P = .03). Moreover, LMP1 expression correlated strongly with IGF-1R expression (P = .018). The relationship between these two biomarkers could influence patient survival. CONCLUSION: IGF1-R and LMP1 could be valuable prognostic markers in Tunisian NPC patients.

Lip reconstruction after cancer resection : clinical study of 70 cases.

BACKGROUND: By virtue of their multiple functions, lips are essential organs. Thus, lip cancers represent a distinct entity in head and neck surgery. Their treatment is fundamentally surgical. We aimed, in this study, to define modalities of repairing techniques of lip defects after surgical resection and post-operative complications. METHODS: We conducted a 4 years retrospective descriptive study including 70 adult patients admitted with lip cancers. RESULTS: Suture, local and regional flaps were the performed techniques for repairing defects (respectively n=28, 35 and 7). The most common postoperative complications were wound dehiscence (n=4), and surgical site necrosis (n=2) and infection (9 patients). Functional sequelae were dominated by microstomia (n=26), (food leakage) (n=9) and gingival exposure (n=11). Aesthetic results were good, fair or poor respectively in 54.3%; 32.9% and 12.8% of patients. CONCLUSION: Lip cancers surgery is relatively well-codified. However, it may be difficult to choose the best repairing technique, especially in case of large lip defect considering functional and aesthetic prejudices.

Bilateral external laryngocele: a case report.

Laryngocele is a rare benign lesion of the larynx caused by an abnormal dilatation of the laryngeal saccule. We report the case of a 78-year-old man presenting bilateral cervical painless soft mass. Bilateral external laryngocele diagnosis was confirmed by CT scan and the patient underwent a surgical resection.

Risk factor of pharyngocutaneous fistula.

INTRODUCTION: Pharyngocutaneous fistula is the most frequent complication of primary and secondary laryngectomy and pharyngolaryngectomy. It has an important impact on the patient, his entourage and the healthcare team. The risk factors for pharyngostoma are multiple and its treatment is not codified. AIM: To identify the various factors that may predispose to this complication and to describe the different therapeutic means to control it. METHODS: This retrospective study examined 68 cases of laryngeal cancer treated by total laryngectomy or pharyngolaryngectomy at Salah Azaїez's head and neck oncologic surgery department between 2015 and 2017. RESULTS: Most of our patients were male (97%) who were major consumer of tobacco and alcohol. The most common stage were T4aN0M0 (34%) and T4aN1M0 (22%). Regarding treatment, we found that 73.5% of patients were operated on by total laryngectomy, 17.7% of patients were operated on by total pharyngolaryngectomy and 8.8% of patients were operated on by square laryngectomy. Pharyngostoma was diagnosed in 20.5% of cases within an average of 15 days. Among the risk factors studied, those that were statistically correlated with the occurrence of CPF in univariate studies were pre-laryngeal infiltration (p = 0.006), postoperative CRP level (p= 0.017), extension to piriform recess (p = 0.009), TNM stage (p=0.039), an associated thyroid surgery (p = 0.020) and pharyngeal closure under tension (p=0.000). In multivariate studies, five of the risk factors identified in the univariate analysis were found. This testifies to their major role as a risk factor for pharyngostoma. These factors were pre-laryngeal infiltration (p=0.001), postoperative CRP level (p=0.000), piriform recess involvement (p=0.004) Associated thyroid surgery (p=0.012) and pharyngeal closure under tension (p = 0.000). CONCLUSION: By identifying predictive factors for pharyngostoma, we can identify patients in which this complication may occur and manage the medical care means to prevent it more efficiently.

Oncologic outcomes of early glottic cancers with anterior commissure involvement treated with advanced laser cordectomies.

INTRODUCTION: The contribution of transoral laser microsurgery (TLM) in the management of early glottic cancer is now well established. The anterior commissure (AC) is a delicate anatomic subsite due to its difficult access and the high risk of tumour spread from this site to the thyroid cartilage, the subglottis and the pre epiglottic space. These reasons make the endoscopic approach controversial in case of AC involvement. METHODS: This is a single centre retrospective study performed between the years 2012 and 2015. Eighteen patients treated with advanced Va laser cordectomies were included. RESULTS: All tumours were staged T1 (78% were T1a and 12% T1b). After laser surgery 4 patients (22.22%) had positive margins. These patients were candidate to second look procedure allowing detection and treatment of residual disease.  Oncologic outcomes were studied. Two patients experienced local relapses within a mean delay of 7 months. The local control rate was 88.9% while the local control using laser only was 83.33%. One patient underwent a total laryngectomy (TL) followed by adjuvant radiation therapy (RT) after a massive recurrence in the AC with infiltration of the thyroid cartilage. The laryngeal preservation rate was 94.44%. The 3 years overall survival rate reached 100% while the 3 years disease free survival was 88.9%. CONCLUSION: the TLM offers acceptable oncologic outcomes in the treatment of T1 laryngeal cancer with AC involvement.

Laryngocele after Subtotal Laryngectomy.

INTRODUCTION: Laryngocele is an air-filled dilatation of the laryngeal saccule that extends upward within the false vocal folds. Different etiologies lead to laryngocele congenital malformation, weakness of the laryngeal tissues and increased intralaryngeal pressure. Laryngocele may be a secondary iatrogenic complication following subtotal laryngectomy. CASE REPORT: We report the case of a 61-year-old patient who presented an external laryngomucocele 8 years after a supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCPL-CHEP). We focus on the clinical aspects and therapeutic attitude, then discuss the physiopathological conditions that could generate this late complication. CONCLUSION: Laryngocele after subtotal laryngectomy should be considered a late iatrogenic complication. Histological examination is necessary after surgical management of laryngocele, as the association with cancer is frequent.

Overexpression of the Oncogenic Variant (KLF6-SV1) in Young NPC Patients and Correlation with Lack of E-Cadherin.

PURPOSE: The transcription factor Krüppel-like factor 6 (KLF6) regulates various cellular functions, such as metabolism, cell proliferation, and differentiation. KLF6 plays a key role in the development and progression of multiple human cancers. METHODS: Fifty primary biopsies and 10 normal nasopharyngeal mucosae were used to analyze by RT-QPCR the expression and the copy number of wtKLF6 and the spliced variants (KLF6-SV1, KLF6-SV2, and KLF6-SV3) in Tunisian patients with nasopharyngeal carcinoma. The expression analysis of E-cadherin and cyclin D1 was conducted by RT-QPCR and Western blot, respectively. RESULTS: The wtKLF6 was significantly downexpressed in tumors compared to normal tissues (p = 0.0015), whereas KLF6-SV1 and KLF6-SV2 were overexpressed in tumors compared to wtKLF6 and KLF6-SV3 (p < 0.0001). Copy number variation was reduced in tumors compared to normal tissues (p = 0.0071). Interestingly, KLF6-SV1 is associated with the juvenile form (p = 0.0003) which is more aggressive than the adult form of NPC. Furthermore, the oncogenic variant KLF6-SV1 was overexpressed in tumors lacking the expression of E-cadherin (p = 0.0022) suggesting its role in metastasis and tumor progression. The wtKLF6 is associated negatively with cyclin D1 in tumor tissues (p = 0.048). CONCLUSION: The wtKLF6 was downexpressed in contrast with the oncogenic variants. Overexpression of KLF6-SV1 is associated with young patients, and loss of E-cadherin suggests that this variant correlated with the aggressiveness of NPC.

HLA-A*26-A*30 and HLA-DRB1*10 could be predictors of nasopharyngeal carcinoma risk in high-risk Tunisian families.

We investigated human leukocyte antigen (HLA) profiles for Tunisians with nasopharyngeal carcinoma (NPC), their families, and a sample of unrelated healthy Tunisians in order to identify HLA specificities associated with familial NPC. HLA-A, -B, and -DRB1 typing was successful for 36 NPC patients, 72 unaffected family members, and 130 community controls, and the chi square or Fisher exact test was used to compare allele frequencies between cases and controls. We observed a consistent protective effect of HLA-DRB1*10 on NPC development. However, none of the NPC patients or their family members had a positive result for this HLA marker (0% vs 9.2% in controls, P = 0.047). In addition, HLA-A*26 was probably an induction marker, as its allelic frequency was significantly higher among NPC patients than among controls (P = 0.003) and among NPC patients than among at-risk family members (P = 0.067). Logistic regression analysis of the joint effect of selected HLA specificities showed that HLA-A*26 and HLA-A*30 were co-associated and have an important effect on NPC risk. Despite the small size of our cohort, we showed that HLA-A*26-A*30 and HLA-DRB1*10 might be predictive markers for NPC screening of Tunisian families with a high risk of NPC.

Polymorphisms in oxidative stress-related genes are associated with nasopharyngeal carcinoma susceptibility.

Nasopharyngeal carcinoma (NPC) is a complex multifactorial disorder involving both genetic and environmental factors. Polymorphisms of genes encoding nitric oxide synthase (NOS) and antioxidant glutathione-S transferases (GSTs) have been associated with various tumors. We examined the combined role of NOS3, NOS2 and GST polymorphisms in NPC risk in Tunisians. We found that NOS3−786C allele and −786 CC genotype, NOS3+894T allele and +894 GT+TT genotypes, NOS2−277 G allele and −277 GG genotype, and GSTT1 del/del genotype, are more prevalent in NPC patients as compared to healthy controls. Our results suggest that genetically driven dysfunction in red­ox stress pathway could augment the risk in NPC-susceptible individuals.

[The value of multimodal imaging by single photon emission computed tomography associated to X ray computed tomography (SPECT-CT) in the management of differentiated thyroid carcinoma: about 156 cases]. / Place de l'imagerie multimodale par tomoscintigraphie couplée au scanner dans la prise en charge des cancers différenciés de la thyroïde: étude sur 156 cas.

BACKGROUND: Single photon emission computed tomography combined with a low dose computed tomography (SPECT-CT), is a hybrid imaging integrating functional and anatomical data. The purpose of our study was to evaluate the contribution of the SPECTCT over traditional planar imaging of patients with differentiated thyroid carcinoma (DTC). METHODS: Post therapy 131IWhole body scan followed by SPECTCT of the neck and thorax, were performed in 156 patients with DTC. RESULTS: Among these 156 patients followed for a predominantly papillary, the use of fusion imaging SPECT-CT compared to conventional planar imaging allowed us to correct our therapeutic approach in 26.9 % (42/156 patients), according to the protocols of therapeutic management of our institute. CONCLUSION: SPECT-CT is a multimodal imaging providing better identification and more accurate anatomic localization of the foci of radioiodine uptake with impact on therapeutic management.

Malar bone metastasis revealing a papillary thyroid carcinoma.

Papillary thyroid carcinoma is the most common form of differentiated thyroid carcinoma. It is generally confined to the neck with or without spread to regional lymph nodes. Metastatic thyroid carcinomas are uncommon and mainly include lung and bone. Metastases involving oral and maxillofacial region are extremely rare. We described a case of malar metastasis revealing a follicular variant of papillary thyroid carcinoma, presenting with pain and swelling of the left cheek in a 67-years-old female patient with an unspecified histological left lobo-isthmectomy medical history. To our knowledge, this is the first recorded instance of a malar metastasis from a follicular variant of papillary thyroid carcinoma.

Complementary determination of Epstein-Barr virus DNA load and serum markers for nasopharyngeal carcinoma screening and early detection in individuals at risk in Tunisia.

Because nasopharyngeal carcinoma (NPC) has a close association with Epstein-Barr virus (EBV), measuring serum EBV DNA and anti-EBV serum marker concentrations could be a feasible method for NPC diagnosis, monitoring and probably screening especially in a community at risk. The aim of this study was to determine the EBV pattern in sporadic NPC and in high risk NPC Tunisian families in order to evaluate their risk factors and help for NPC screening. The rates of anti-EBV antibodies and EBV DNA were determined in the serum of 47 healthy members randomly selected from 23 NPC multiplex families with two or more affected members, 93 healthy Tunisian community controls chosen with the same age, sex and geographic origin as unaffected individuals and 66 EBV positive sporadic NPC patients whose serum was available before and after treatment. Unexpectedly, significant lower concentrations of anti-EA (Early Antigen) IgG and anti-VCA (Viral Capsid Antigen) IgG were found in unaffected members from NPC families than in healthy controls while viral loads were negative in all the tested sera. For sporadic NPC patients, anti-EA IgG and anti-VCA IgA concentrations were significantly higher than in healthy controls and these rates decreased after treatment. The level of EBV DNA load varied according to the condition of the tumour. This study suggests that in the Tunisian NPC families, screening for malignancy is based on serum concentrations but not on EBV DNA load while in the sporadic NPC group, serologic markers and EBV DNA load are complementary for diagnosis and follow-up.

Nasopharyngeal cancer (NPC) around the Mediterranean area: standard of care.

Mediterranean area (MA) represents a zone of intermediate incidence (1-5/100,000) for NPC, the highest frequency being observed in North Africa (NA) where it is characterized by a bimodal age repartition due to a first adolescence peak. In MA and NA, NPC remain diagnosed at advanced stages which impact poorly on overall and disease-free survival. It's therapy in MA followed the progresses and standardisation of protocols, based on concomitant chemoradiotherapy (CCRT) alone or preceded by induction chemotherapy (ICT) in advanced (N2-3, T3-4) stages, while localized cases are managed irradiation alone. NPC overall an disease-free survival improved, due to the use of combined chemo and radiotherapy.

[Update on medical therapies of nasopharyngeal carcinomas]. / Actualités des traitements médicaux des cancers du nasopharynx.

Nasopharyngeal carcinomas (NPC) are predominantly of undifferentiated type (UCNT or undifferentiated carcinoma of nasopharyngeal type), rare (<1/100,000) and sporadic in occidental countries, but endemic in the Mediterranean area of intermediate incidence (2 to 10/100,000) and highly frequent (>10/100,000) in South East Asia. NPC staging is based on TNM UICC 2002 that has a prognostic and therapeutic orientation impact. Irradiation of the primitive tumor and its extensions remains the standard loco-regional treatment. The recent introduction of primary and concomitant chemotherapy leads to an improvement in terms of overall and disease-free survival, specially for for high-risk-patients (T3-4 and N2-3 disease). Prognosis remain linked to T, N, histologic type and quality of response to chemotherapy and radiotherapy.

Head and neck liposarcomas: a 32 years experience.

OBJECTIVE: The aim of this review is to study natural history, presentation, treatment and prognosis of head and neck liposarcomas. METHODS: We carry a retrospective study about 15 patients diagnosed and treated in our department between 1969 and 2001. Therapeutic modalities included surgery, radiotherapy and chemotherapy. RESULTS: Tumors were mostly localized at the neck (4 cases) and the scalp (3 cases). Cervical lymphadenopathy was found in 1 case. Chest X-ray found showed metastases in 2 cases. Histological types of liposarcomas were the following: myxoid (5 cases), well differentiated (4 cases), pleomorphic (4 cases), round cell (1 case) and dedifferentiated (1 case). Twelve patients underwent surgery. Complete excision was performed in 7 cases. In the other 5 cases, exeresis was incomplete and 4 of them received postoperative radiotherapy. Three patients were not operated because of vascular involvement (1 case) or metastasis (2 cases), and they all received radiotherapy alone. After initial treatment, complete remission was achieved in 7 cases (46.7%). A recurrence occurred in 8 cases (53.3%). Two of these patients were reoperated and another one received chemotherapy. In the other 5 cases, the tumor was uncontrollable and no additional treatment has been proposed. Five-year survival rate was 87% for patients who underwent surgery alone, 75% for those who underwent surgery and postoperative radiotherapy, and 0% for those treated by radiotherapy alone. CONCLUSION: The mainstay of treatment of head and neck liposarcomas is surgical excision and the prognosis is largely determined by the histological grade and the clinical stage.