L’apport de l’imagerie hybride TEMP/TDM dans la prise en charge du cancer différencié de la thyroïde

IntroductionSingle 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 SPECT/CT over traditional planar imaging of patients with differentiated thyroid carcinoma (DTC).MethodsPost-therapy iodine 131 (¹³¹I) whole-body scan followed by cervico-thoracic SPECT/CT, were performed in 100 patients with DTC.ResultsAmong these 100 patients followed for a predominantly papillary DTC, planar imaging and SPECT/CT, were perfectly concordant in 70% of patients and discordant in the remaining 30%. The use of fusion imaging SPECT/CT compared to conventional planar imaging allowed us to correct our therapeutic approach in 27% (27/100 patients), according to the protocols of therapeutic management of our institute.ConclusionSPECT/CT is a hybrid imaging modality which provides better identification and more correct anatomic localization of the foci of radioiodine uptake with impact on therapeutic management.     

First report of molecular diagnosis of Tunisian hemophiliacs A: identification of 8 novel causative mutations

ABSTRACT: INTRODUCTION: Hemophilia A is an X linked recessive hemorrhagic disorder caused by mutations in the F8 gene that lead to qualitative and/or quantitative deficiencies of coagulation factor VIII (FVIII). Molecular diagnosis of hemophilia A is challenging because of the high number of different causative mutations that are distributed throughout the large F8 gene. Molecular studies of these mutations are essential in order to reinforce our understanding of their pathogenic effect responsible for the disorder. Aim In this study we have performed molecular analysis of 28 Tunisian hemophilia A patients and analyzed the F8 mutation spectrum. METHODS: We screened the presence of intron 22 and intron 1 inversion in severe hemophilia A patients by southern blotting and polymerase chain reaction (PCR). Detection of point mutations was performed by dHPLC/sequencing of the coding F8 gene region. We predict the potential functional consequences of novel missense mutations with bioinformatics approaches and mapping of their spatial positions on the available FVIII 3D structure. RESULTS: We identified 23 different mutations in 28 Tunisian hemophilia A patients belonging to 22 unrelated families. The identified mutations included 5 intron 22 inversions, 7 insertions, 4 deletions and 7 substitutions. In total 18 point mutations were identified, of which 9 are located in exon 14, the most mutated exonic sequence in the F8 gene. Among the 23 mutations, 8 are novel and not deposited in the HAMSTeRS database nor described in recently published articles. CONCLUSION: The mutation spectrum of Tunisian hemophilia A patients is heterogeneous with the presence of some characteristic features. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1693269827490715.     

Évaluation de l’irradiation additionnelle des patients de médecine nucléaire en imagerie hybride TEMP/TDM

One hundred and ten consecutive patients and 130 SPECT/CT examinations were involved in this retrospective study that focused on the evaluation of the excess of dose contributed by the CT to the patient during the SPECT/CT explorations, for routine examinations in nuclear medicine. The average age of patients was 53 years. In this study, it appeared that irradiation induced by a low dose CT combined with a SPECT is low compared to that of a diagnostic CT. The main risk on patients is the occurrence of radiation-induced cancer. In our study, this increased risk induced by the additional CT with low dose settings in line with SPECT examination, is not significant and does not exceed 0.026%. By weighing the diagnostic value of SPECT/CT examination with that of a stand-alone SPECT examination dosimetric “incremental cost” is justified because of its direct clinical benefit conveyed to the patient.     

Cytogenetic analysis in 139 Tunisian patients with de novo acute myeloid leukemia

This paper presents the results of a cytogenetic analysis in 139 Tunisian patients with de novo acute myeloid leukemia (AML), including 27 children aged 1-15 years and 112 adults. Mean age was 32 (range 1-75) and the M/F ratio was 1.43. Of our patients, 45% had apparently normal karyotypes. Acquired chromosome aberrations were found in 77 (55% ) patients. t(8;21) was identified in 27 patients (19%); t(15;17) in 13 patients (9%); deletion 7q or monosomy 7 in seven patients (5%); +8 in seven patients (5%); abnormal 16 in four patients (3%); 11q23 rearrangements in two patients (2%) and del(5q), in one patient (1%). The remaining 16 patients had miscellaneous clonal abnormalities. Specific translocations associated with the FAB type were found: t(8;21) with AML2 and t(15;17) with AML3. We concluded that our study in a Tunisian population confirmed the relation between some specific abnormalities and the FAB classification. We found a higher incidence for t(8;21) than usually described.     

Identification of novel candidate genes by exome sequencing in Tunisian familial male breast cancer patients

Molecular Biology Reports - Male Breast Cancer (MBC) is a rare and aggressive disease that is associated with genetic factors. Mutations in BRCA1 and BRCA2 account for...     

Molecular cytogenetic aberrations in Tunisian patients with multiple myeloma identified by cIg-FISH in fixed bone marrow cells

Cytogenetic studies in multiple myeloma (MM) are hampered by the hypo-proliferative nature of plasma cells. In order to circumvent this problem, we have used a combination of immunolabeling of cytoplasmic Ig light chains (λ or κ) and FISH (cIg-FISH), which allowed a comprehensive detection of the most common and/or recurrent molecular cytogenetic aberrations on fixed bone marrow cells of 70 Tunisian patients. Translocations involving the chromosome 14q32 region were observed in 32 cases (45.7%), including 18 cases with a t(11;14), 8 cases with a t(4;14), and 2 cases with a t(14;16). Deletions of the 13q14 region (D13S319/RB1) were detected in 18.6%, and deletions of the 17p13 region (TP53) in 5.7% of the cases, respectively. Of all patients with a D13S319/RB1 deletion, 61.5% also carried a 14q32 translocation, whereas TP53 deletions were associated with a t(11;14) in 2 cases (50%) and a D13S319 deletion in 1 case (25%). Our results suggest that there is a correlation between the presence of 14q32 translocations and chromosome 13q14 deletions in MM patients and that cIg-FISH is more sensitive as compared to conventional karyotyping in detecting molecular cytogenetic abnormalities in this disease.     

Le cancer différencié de la thyroïde chez les patients de moins de 20 ans : à propos de 20 cas

Papillary thyroid cancer is rare in patients under 20 years and has a good prognosis, although it is often found at the stage of lung metastases. Our multicenter study included 20 patients aged between 5 and 18 years, female predominance, followed for differentiated thyroid cancer with lung metastases. All these patients underwent a whole body scan with I-131, serum thyroglobulin, chest radiography in 4 cases and cervico-thoracic (CT) in 5 cases. Only scintigraphic imaging has shown miliary pulmonary among all patients. The therapeutic efficacy was observed in all patients after treatment with iodine-131, which proves the high sensitivity of these metastases to irathérapie. The differentiated thyroid cancer in child and adolescent is characterized by local aggressiveness and a higher frequency of distant metastases than in the adult. Prognosis does not seem to be influenced by histology alone, but by its association with other prognostic factors: age, metastases and surgery.     

Apport de l’imagerie hybride TEMP-TDM dans le suivi d’un cancer différencié de la thyroïde

In the management of patients with differentiated thyroid cancer (DTC), abnormalities detected on planar whole body scan and ¹³¹I-SPECT are difficult to interpret because of a lack of anatomical landmarks and limited specificity. Integrated ¹³¹I-SPECT-CT imaging has an additional value for characterization of equivocal tracer uptake seen on planar imaging as well as for precise localization. We illustrate through an observation the incremental diagnostic value of ¹³¹I-SPECT-CT images in the diagnosis of a cervical lymph node mimicking a physiological uptake on planar views. A 35-year-old Tunisian female was followed for papillary thyroid carcinoma, for which she underwent total thyroidectomy and iratherapy. Three years after a complete remission, the thyroglobulin (Tg) level on TSH stimulation increased. Diagnostic planar images with ¹³¹I did not disclose any obvious pathological foci. Furthermore, we noticed an increased ¹³¹I-uptake in the left sub-mandibulary area, which suggested a salivary physiological activity. SPECT-CT of the neck and chest were then performed with a Symbia T camera. Fused images demonstrate that this activity corresponds to a cervical lymph node closely adjacent to sub-mandibulary gland. Management of the patient was then changed. In selected patients with DTC, hybrid imaging should be used as a complementary to planar imaging in terms of diagnostic accuracy, because of superior focus localization and additional anatomic information derived from the CT component. Integrated SPECT-CT is then a useful tool, especially in cases of unclear diagnoses, precising anatomical localization of areas of increased ¹³¹I-uptake and distinguishing malignant lesions from normal physiological uptakes. This is particularly important in an oncologic center, as ours, where we don’t yet have a positron emission tomography (PET) camera is not yet available.     

Targeting stem cells by radiation: From the biological angle to clinical aspects

Radiotherapy is a cornerstone of anticancer treatment. However in spite of technical evolutions, important rates of failure and of toxicity are still reported. Although numerous pre-clinical data have been published, we address the subject of radiotherapy-stem cells interaction from the clinical efficacy and toxicity perspective. On one side, cancer stem cells(CSCs) have been recently evidenced in most of solid tumor primary locations and are thought to drive radio-resistance phenomena. It is particularly suggested in glioblastoma, where CSCs were showed to be housed in the subventricular zone(SVZ). In recent retrospective studies, the radiation dose to SVZ was identified as an independent factor significantly influencing overall survival. On the other side, healthy tissue stem cells radio-destruction has been recently suggested to cause two of the most quality of life-impacting side effects of radiotherapy, namely memory disorders after brain radiotherapy, and xerostomia after head and neck radiotherapy. Recent publications studying the impact of a radiation dose decrease on healthy brain and salivary stem cells niches suggested significantly reduced long term toxicities. Stem cells comprehension should be a high priority for radiation oncologists, as this particular cell population seems able to widely modulate the efficacy/toxicity ratio of radiotherapy in real life patients.