Prognostic value of tumor mutational burden in patients with oral cavity squamous cell carcinoma treated with upfront surgery.

BACKGROUND: Oral cavity is the most prevalent site of head and neck squamous cell carcinomas (HNSCCs). Most often diagnosed at a locally advanced stage, treatment is multimodal with surgery as the cornerstone. The aim of this study was to explore the molecular landscape of a homogenous cohort of oral cavity squamous cell carcinomas (OCSCCs), and to assess the prognostic value of tumor mutational burden (TMB), along with classical molecular and clinical parameters. PATIENTS AND METHODS: One hundred and fifty-one consecutive patients with OCSCC treated with upfront surgery at the Institut Curie were analyzed. Sequencing of tumor DNA from frozen specimens was carried out using an in-house targeted next-generation sequencing panel (571 genes). The impact of molecular alterations and TMB on disease-free survival (DFS) and overall survival (OS) was evaluated in univariate and multivariate analyses. RESULTS: Pathological tumor stage, extranodal spread, vascular emboli, and perineural invasion were associated with both DFS and OS. TP53 was the most mutated gene (71%). Other frequent molecular alterations included the TERT promoter (50%), CDKN2A (25%), FAT1 (17%), PIK3CA (14%), and NOTCH1 (15%) genes. Transforming growth factor-ß pathway alterations (4%) were associated with poor OS (P = 0.01) and DFS (P = 0.02) in univariate and multivariate analyses. High TMB was associated with prolonged OS (P = 0.01 and P = 0.02, in the highest 10% and 20% TMB values, respectively), but not with DFS. Correlation of TMB with OS remained significant in multivariate analysis (P = 0.01 and P = 0.005 in the highest 10% and 20% TMB values, respectively). Pathological tumor stage combined with high TMB was associated with good prognosis. CONCLUSION: Our results suggest that a high TMB is associated with a favorable prognosis in patients with OCSCC treated with upfront surgery.

Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial.

Squamous cell carcinomas (SCCs) are among the most frequent solid tumors in humans. SCCs, related or not to the human papillomavirus, share common molecular features. Immunotherapies, and specifically immune checkpoint inhibitors, have been shown to improve overall survival in multiple cancer types, including SCCs. However, only a minority of patients experience a durable response with immunotherapy. Epigenetic modulation plays a major role in escaping tumor immunosurveillance and confers resistance to immune checkpoint inhibitors. Preclinical evidence suggests that modulating the epigenome might improve the efficacy of immunotherapy. We herein review the preclinical and the clinical rationale for combining immunotherapy with an epidrug, and detail the design of PEVOsq, a basket clinical trial combining pembrolizumab with vorinostat, a histone deacetylase inhibitor, in patients with SCCs of different locations. Sequential blood and tumor sampling will be collected in order to identify predictive and pharmacodynamics biomarkers of efficacy of the combination. We also present how clinical and biological data will be managed with the aim to enable the development of a prospective integrative platform to allow secure and controlled access to the project data as well as further exploitations.

Can FDG-PET/MR help to overcome limitations of sequential MRI and PET-FDG for differential diagnosis between recurrence/progression and radionecrosis of high-grade gliomas?

The aim of our study was assessing the potential of FDG-PET-MRI to overcome limitations of separately performed MRI and PET-FDG and improving the performance of high-grade gliomas evaluation. Combined PET-MRI analysis allowed differentiating between recurrence/progression and radionecrosis with improved diagnostic accuracy (95% vs 63% for PET and 82% for MRI). FDG being a reliable, cost-saving tracer in this indication, combined FDG PET-MRI analysis could play a significant role in the follow-up of high-grade brain tumors.

Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate Idiopathic Parkinson Disease.

BACKGROUND AND PURPOSE: Several new MR imaging techniques have shown promising results in patients with Parkinson disease; however, the comparative diagnostic values of these measures at the individual level remain unclear. Our aim was to compare the diagnostic value of MR imaging biomarkers of substantia nigra damage for distinguishing patients with Parkinson disease from healthy volunteers. MATERIALS AND METHODS: Thirty-six patients and 20 healthy volunteers were prospectively included. The MR imaging protocol at 3T included 3D T2-weighted and T1-weighted neuromelanin-sensitive images, diffusion tensor images, and R2* mapping. T2* high-resolution images were also acquired at 7T to evaluate the dorsal nigral hyperintensity sign. Quantitative analysis was performed using ROIs in the substantia nigra drawn manually around the area of high signal intensity on neuromelanin-sensitive images and T2-weighted images. Visual analysis of the substantia nigra neuromelanin-sensitive signal intensity and the dorsolateral nigral hyperintensity on T2* images was performed. RESULTS: There was a significant decrease in the neuromelanin-sensitive volume and signal intensity in patients with Parkinson disease. There was also a significant decrease in fractional anisotropy and an increase in mean, axial, and radial diffusivity in the neuromelanin-sensitive substantia nigra at 3T and a decrease in substantia nigra volume on T2* images. The combination of substantia nigra volume, signal intensity, and fractional anisotropy in the neuromelanin-sensitive substantia nigra allowed excellent diagnostic accuracy (0.93). Visual assessment of both substantia nigra dorsolateral hyperintensity and neuromelanin-sensitive images had good diagnostic accuracy (0.91 and 0.86, respectively). CONCLUSIONS: The combination of neuromelanin signal and volume changes with fractional anisotropy measurements in the substantia nigra showed excellent diagnostic accuracy. Moreover, the high diagnostic accuracy of visual assessment of substantia nigra changes using dorsolateral hyperintensity analysis or neuromelanin-sensitive signal changes indicates that these techniques are promising for clinical practice.

Reproducibility of R2 * and quantitative susceptibility mapping (QSM) reconstruction methods in the basal ganglia of healthy subjects.

The basal ganglia are key structures for motor, cognitive and behavioral functions. They undergo several changes with aging and disease, such as Parkinson's or Huntington's disease, for example. Iron accumulation in basal ganglia is often related to these diseases, which is conventionally monitored by the transverse relaxation rate (R2 *). Quantitative susceptibility mapping (QSM) is a novel contrast mechanism in MRI produced by adding information taken from the phase of the MR signal to its magnitude. It has been shown to be more sensitive to subtle changes in Parkinson's disease. In order to be applied widely to various pathologies, its reproducibility must be evaluated in order to assess intra-subject variability and to disseminate into clinical and pharmaceutical studies. In this work, we studied the reproducibility and sensitivity of several QSM techniques. Fourteen subjects were scanned four times, and QSM and R2 * images were reconstructed and registered. An atlas of the basal ganglia was used to automatically define regions of interest. We found that QSM measurements are indeed reproducible in the basal ganglia of healthy subjects and can be widely used as a replacement for R2 * mapping in iron-rich regions. This reproducibility study could lead to several lines of research in relaxometry and susceptibility measurements, in vivo iron load evaluation as well as pharmacological assessment and biomarker development. Copyright © 2016 John Wiley & Sons, Ltd.

[Problematic Internet use among teenagers in Sfax, Tunisia]. / Prévalence de l'usage problématique d'Internet chez les adolescents, Sfax, Tunisie.

UNLABELLED: Use of the Internet in Tunisian society and especially among teenagers has increased in recent years. While the use of Internet is primarily intended for research and communication, the Internet has also become an important part of teenager's life. Most people use the Internet in healthy and productive ways. However, some teenagers develop a problematic use of the Internet, which is a condition also known by the term of "Internet addiction". In Tunisia, the literature does not report data on problematic Internet use prevalence among Tunisian teenagers. PURPOSE: The aim of this study was to determine the prevalence of problematic Internet use among teenagers, in the urban area of Sfax. METHODS: This transversal study was carried out between the 15th January and the 15th February 2009. Participants were 600, first to third grade secondary school students, aged 14 to 20. They were recruited from seven secondary schools randomly selected in the urban area in Sfax City. The self-administered Young's 8-item questionnaire was used in this survey. Participants who scored five or more can be considered problematic Internet users. Finally, 587 valid data samples were collected, 263 (44%) males and 324 (56%) females. Eighty-five percent of the participants were in the 15-17 age range. The mean age was 16 years (±1.26). RESULTS: The prevalence of problematic Internet use was 18.05% (total of 587 students). The sex-ratio was 0.75. The problematic Internet use was not correlated with sex. The average time of Internet use per day among problematic Internet users was 4.5hours (±2.84) against 1.02hours (±1.56) among non problematic Internet users (P=0.000). DISCUSSION: In this study, the prevalence of problematic Internet use was higher than that reported in previous studies. Two facts can explain this: first, the use of the only self-administered questionnaire does not distinguish between a simple abuse and a problematic Internet use. A psychiatric examination is essential to support the diagnosis of problematic Internet use. Second, this study was conducted exclusively in an urban area where access to the Internet is easier than in rural areas. This study was not representative of teenagers in Sfax. The gender difference was consistent with the findings of prior research, as was the average time of Internet use per day among problematic Internet users. CONCLUSION: This study shows that problematic Internet use is frequent in our teenage population. A preventive outreach for youths, their families and health professionals is needed to limit the extension of this problem among young people. The existence of misuse of the Internet should not lead to avoiding this media. Reflections on how to moderate the relationship with the Internet are necessary; especially since Internet becomes an essential medium of information and communication. The current lack of Internet education in school curricula is also a shortage to fulfil.

Algorithm for detection of the internal components of the heart sounds and their split using a Hilbert transform.

Valvular heart disease is a serious heart condition that is difficult to diagnose in ambulatory settings. Heart sounds is one of the most relevant diagnosis signals in this context. The time interval between the two internal components of the two heart sounds in the medical field known as 'split' was considered by many researchers and one study is described as the key medical diagnosis by many clinicians. Compared to the energy envelope Shannon Hilbert envelope is greater awareness of the internal components of the first and second heart sound. The morphology of this envelope will allow one to apply the necessary tests for the temporal localization of the internal components of the two heart sounds. According to the results obtained, the Hilbert envelope is an approach and representation taking into account the physiological attenuation and giving a good separation.

[Malignant pheochromocytomas: about three cases]. / Les phéochromocytomes malins: à propos de trois observations.

The authors report three cases of malignant pheochromocytomas. Metastases occurred in the liver in two cases whereas malignancy was suspected in the third case because of recurrence and local invasion. One case was pregnant at diagnosis of pheochromocytoma. Pheochromocytoma was associated to papillary thyroïd carcinoma in another case. The treatment considered was surgery in all cases.

[Etiologic and therapeutic aspects of acquired central diabetes insipidus]. / Aspects étiologiques et thérapeutiques du diabète insipide central acquis.

Acquired central diabetes insipidus (CDI) is a rare disease due to anatomic lesions of the hypothalamo-pituitary system. We discuss the etiologic and therapeutic aspects of CDI. Through 5 cases and a review of the literature. We report: Two cases of Langerhans histiocytosis, a 21 year old man and a 37 year old women. The CDI was the only endocrine manifestation in the man, but it was associated with panhypopituitarism and infiltration of the thyroid gland by histiocytosis cells in the women. One case of suprasellar germinoma, a 18 year old adolescent had hypocorticism, hypothyroidism, and hypogonadism associated with CDI and hyperprolactinemia. One case of pituitary cystic lesion with extension to the suprasellar area, a 36 year old women presenting with hypocorticism, growth hormone deficiency, and hyperprolactinemia. One case of neuro-Behçet's disease in a 47 year old man. He presented with strokes and CDI. When the CDI is isolated Langerhans Histiocytosis should be considered first. The exploration of the hypothalamo-pituitary region using MRI showed different anatomic lesions in patients with CDI. It is very difficult to determine definitive diagnosis before surgery in the cases of cystic lesions.

[Ectopic thyroid: two cases]. / L'ectopie thyroïdienne: à propos de deux cas.

Ectopic thyroid is a rare condition (1/4000 to 1/8000 among patients with hypothyroidism). The underlying etiological pathogenic mechanisms remain unknown. Diagnosis is established on the basis of imaging findings. We report two cases of hypothyroidism in adult females who had ectopic sublingual thyroid glands. The first patient was a 20-Year-old woman who had been treated for hypothyroidism since the age of 13 Years before the diagnosis of ectopic thyroid 7 Years later. In both patients, the thyroid gland was palpable. In the first patient the physical examination revealed an ectopic sublingual gland. Scintigraphy confirmed the diagnosis in both patients. The CT-scan and MRI were positive in the second patient. Hormonal substitution therapy using L-thyroixine was given.

[Virilism during pregnancy]. / Virilisme au cours de la grossesse: à propos d'un cas.

We discuss the causes of virilism in pregnancy and the impact of hyperandrogeny on the female foetus. We report a case of virilism in a 28-year-old, gravida 1, para 1 patient with normal pregnancy and review the literature. After conception, the patient had been well until the 18th week of gestation, when she developed signs of virilization; her serum testosterone was markedly elevated. She delivered of a normal male infant at term. After delivery, signs of virilization regressed with normalization of testosterone level but a wide mass of the left ovary that persisted for 8 months. The histological study of the tumor showed luteinized thecoma. Luteomas and hyper-reactio luteinalis were the principal causes of virilism in pregnancy, thecomas are rare.

[Obstructive acute renal failure revealing visceral leishmaniasis in a diabetic patient]. / Une insuffisance rénale aiguë obstructive révélant une leishmaniose viscérale chez un diabétique.

We report a case of a 22 years old type 1 diabetic man with a history of weight loss, weakness, anorexia, fever and recurrent urinary tract infection since February 2001. In April 2001, he presented anuria due to obstructive acute renal failure. Hepatosplenomegaly and lymphadenopathy were absent at physical examination. Laboratory tests revealed a high level of gamma globulin (53.4 g/l) and anaemia (haemoglobin 7.7 g/100 ml) without leukopenia and thrombocytopenia. CT scan showed multiple retroperitoneal lymphadenopathies causing compression of the two ureters, hydro-ureter associated with hydronephrosis, hepatosplenomegaly and multiple pulmonary nodes. Lymphadenopathies, anaemia, high level of gamma globulin, high titres of anti-leishmanial antibodies and the excellent outcome after treatment with meglumine antimoniate (Glucantime) confirmed visceral leishmaniasis. This report documented an unusual clinical presentation of Visceral leishmaniasis in a diabetic patient.

[Central diabetes insipidus with Behçet disease. A case report]. / Diabète insipide central en rapport avec une maladie de Behçet. A propos d'un cas.

Vasculitis with central diabetes insipidus is a rare condition which must be recognized for an appropriate management. We report a case of Behçet disease with central diabetes insipidus. A forty seven year old men presented recurring oral and genital ulcers, skin lesions, polyarthralgia. Two years later, he showed right uveitis and central diabetes insipidus without dysfunction of the pituitary gland. Computed tomographic scan showed normal neurohypophysis and pituitary gland. Later on, he presented hemiplegia. The cerebral computed tomographic scan showed hypodense lesions. Central diabetes insipidus should not be systematically searched because it is a rare feature of the Behçet disease.

[Diabetic fibrous mastopathy: a case report]. / Mastopathie fibreuse diabétique.

Diabetic fibrous mastoplasty or diabetic fibrous breast disease is a benign condition rarely observed. First described in 1984, it can lead to misdiagnosis because it simulates breast cancer. Diabetic fibrous mastoplasty usually occurs in patients with autoimmune disorders, particularly in patients with longstanding and complicated insulin-dependent diabetes mellitus. We present a case of fibrous mastoplasty in a patient with insulin-dependent diabetes mellitus known for 17 years. The clinical and radiological features and the clinical course are illustrative. We discuss the different pathogenic theories put forward.