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Background: Metastatic castration-resistant prostate cancer (mCRPC) remains uniformly lethal. Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein overexpressed in prostate cancer. 131 I-PSMA-1095 (also known as 131 I-MIP-1095) is a PSMA-targeted radioligand which selectively delivers therapeutic radiation to cancer cells and the tumor microenvironment., Methods: We conducted a single-arm, phase 2 trial to assess efficacy and tolerability of 131 I-PSMA-1095 in mCRPC patients who had exhausted all lines of approved therapy. All patients underwent 18 F-DCFPyL PET and 18 F-FDG PET to determine PSMA-positive tumor volume, and patients with >50% PSMA-positive tumor volume were treated with up to four doses of 131 I-PSMA-1095. The primary endpoint was the response rate of prostate specific antigen (PSA). Secondary endpoints included rates of radiographic response and adverse events. Overall and radiographic progression-free survival were also analyzed., Results: Eleven patients were screened for inclusion and nine patients received 131 I-PSMA-1095. The median baseline PSA was 162 µg/l, and six patients demonstrated a >50% PSA decrease. One patient demonstrated a confirmed radiographic response. Median overall survival was 10.3 months, and median progression-free survival was 5.4 months. Four patients experienced adverse events of grade 3 or higher, the most frequent being thrombocytopenia and anemia., Conclusion: 131 I-PSMA-1095 is highly active against heavily-pretreated PSMA-positive mCRPC, significantly decreasing tumor burden as measured by PSA. Adverse events, mainly hematologic toxicity, were not infrequent, likely related to off-target irradiation. This hematologic toxicity, as well as a higher logistical burden associated with use, could represent relative disadvantages of 131 I-PSMA-1095 compared to 177 Lu-PSMA-617., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Climate change is a global problem facing all aspects of the agricultural sector. Heat stress due to increasing atmospheric temperature is one of the most common climate change impacts on agriculture. Heat stress has direct effects on crop production, along with indirect effects through associated problems such as drought, salinity, and pathogenic stresses. Approaches reported to be effective to mitigate heat stress include nano-management. Nano-agrochemicals such as nanofertilizers and nanopesticides are emerging approaches that have shown promise against heat stress, particularly biogenic nano-sources. Nanomaterials are favorable for crop production due to their low toxicity and eco-friendly action. This review focuses on the different stresses associated with heat stress and their impacts on crop production. Nano-management of crops under heat stress, including the application of biogenic nanofertilizers and nanopesticides, are discussed. The potential and limitations of these biogenic nano-agrochemicals are reviewed. Potential nanotoxicity problems need more investigation at the local, national, and global levels, as well as additional studies into biogenic nano-agrochemicals and their effects on soil, plant, and microbial properties and processes.

Baked pretzels are a popular choice for a quick snack, easily identifiable by their classic twisted shape, glossy exterior, and small salt crystals sprinkled on top, making them a standout snack. However, it is not commonly known that compounds with fluorescent properties can be formed during their production. Carbon nanodots (CNDs) with an average size of 3.5 nm were isolated and identified in bakery products. This study delved into the formation of CNDs in pretzel production using a fractional factorial experimental design. The research revealed that the baking temperature had the most significant impact on the concentration of CNDs, followed by the concentration of NaOH in the immersion solution, and then the baking time. This study highlights the unique role of the NaOH immersion step, which is not typically present in bread-making processes, in facilitating the formation of CNDs. This discovery highlights the strong correlation between the formation of CNDs and the heat treatment process. Monitoring and controlling these factors is crucial for regulating the concentration of CNDs in pretzel production and understanding nanoparticle formation in processed foods for food safety.

The time-consuming nature of culturing methods has urged the exploration of rapid modern technologies. One promising alternative utilizes redox potential, which describes the oxidative changes within complex media, indicating oxygen and nutrient consumption, as well as the production of reduced substances in the investigated biological system. Redox potential measurement can detect microbial activity within 16 h, what is significantly faster than the minimum 24 h incubation time of the reference plate counting technique. The redox potential based method can be specific with selective media, but bacterial strains have unique kinetic pattern as well. The proposed method suggests evaluation of the curve shape for the differentiation of environmental contaminant and pathogenic microbial strains. Six bacterial species were used in validation ( Escherichia coli , Pseudomonas aeruginosa, Salmonella enterica, Listeria innocua, Listeria monocytogenes, and Listeria ivanovii ). Descriptive parameters reached 98.2 % accuracy and Gompertz model achieved 91.6 % accuracy in classification of the selected 6 bacteria species.•Mathematical model (Gompertz function) and first order descriptive parameters are suggested to describe the specific shape of redox potential curves, while Support Vector Machine (SVM) is recommended for classification.•Due to the concentration dependent time to detection (TTD), pre-processing applies standardization according to the inflection point time., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Introduction: Cancer management in Africa faces diverse challenges due to limited resources, health system challenges, and other matters. Identifying hereditary cancer syndromic cases is crucial to improve clinical management and preventive care in these settings. This study aims to explore the clinicopathological features and genetic factors associated with hereditary cancer in Tunisia, a North African country with a rising cancer burden MATERIALS AND METHODS: Clinicopathological features and personal/family history of cancer were explored in 521 patients. Genetic analysis using Sanger and next-generation sequencing was performed for a set of patients RESULTS: Hereditary breast and ovarian cancer syndrome was the most frequent cluster in which 36 BRCA mutations were identified. We described a subgroup of patients with likely ''breast cancer-only syndrome'' among this cluster. Two cases of Li-Fraumeni syndrome with distinct TP53 mutations namely c.638G>A and c.733G>A have been identified. Genetic investigation also allowed the identification of a new BLM homozygous mutation (c.3254dupT) in one patient with multiple primary cancers. Phenotype-genotype correlation suggests the diagnosis of Bloom syndrome. A recurrent MUTYH mutation (c.1143_1144dup) was identified in three patients with different phenotypes CONCLUSION: Our study calls for comprehensive genetic education and the implementation of genetic screening in Tunisia and other African countries health systems, to reduce the burden of hereditary diseases and improve cancer outcomes in resource-stratified settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Early detection of cardiovascular diseases is based on accurate quantification of the left ventricle (LV) function parameters. In this paper, we propose a fully automatic framework for LV volume and mass quantification from 2D-cine MR images already segmented using U-Net., Methods: The general framework consists of three main steps: Data preparation including automatic LV localization using a convolution neural network (CNN) and application of morphological operations to exclude papillary muscles from the LV cavity. The second step consists in automatically extracting the LV contours using U-Net architecture. Finally, by integrating temporal information which is manifested by a spatial motion of myocytes as a third dimension, we calculated LV volume, LV ejection fraction (LVEF) and left ventricle mass (LVM). Based on these parameters, we detected and quantified cardiac contraction abnormalities using Python software., Results: CNN was trained with 35 patients and tested on 15 patients from the ACDC database with an accuracy of 99,15 %. U-Net architecture was trained using ACDC database and evaluated using local dataset with a Dice similarity coefficient (DSC) of 99,78 % and a Hausdorff Distance (HD) of 4.468 mm (p < 0,001). Quantification results showed a strong correlation with physiological measures with a Pearson correlation coefficient (PCC) of 0,991 for LV volume, 0.962 for LVEF, 0.98 for stroke volume (SV) and 0.923 for LVM after pillars' elimination. Clinically, our method allows regional and accurate identification of pathological myocardial segments and can serve as a diagnostic aid tool of cardiac contraction abnormalities., Conclusion: Experimental results prove the usefulness of the proposed method for LV volume and function quantification and verify its potential clinical applicability., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 IPEM. Published by Elsevier Ltd. All rights reserved.)

Objectives: Immune checkpoint inhibitors (ICIs) are indicated for metastatic urothelial cancer (mUC), but predictive and prognostic factors are lacking. We investigated clinical variables associated with ICI outcomes., Methods: We performed a multicentre retrospective cohort study of 135 patients who received ICI for mUC, 2016-2021, at three Canadian centres. Clinical characteristics, body mass index (BMI), metastatic sites, neutrophil-to-lymphocyte ratio (NLR), response and survival were abstracted from chart review., Results: We identified 135 patients and 62% had received ICI as a second-line or later treatment for mUC. A BMI ≥25 was significantly correlated to a higher overall response rate (ORR) (45.4% vs 16.3%, p value=0.020). Patients with BMI ≥30 experienced longer median overall survival (OS) of 24.8 vs 14.4 for 25≤BMI<30 and 8.5 months for BMI <25 (p value=0.012). The ORR was lower in the presence of bone metastases (16% vs 41%, p value=0.006) and liver metastases (16% vs 39%, p value=0.013). Metastatic lymph nodes were correlated with higher ORR (40% vs 20%, p value=0.032). The median OS for bone metastases was 7.3 versus 18 months (p value <0.001). Patients with liver metastases had a median OS of 8.6 versus 15 months (p value=0.006). No difference for lymph nodes metastases (13.5 vs 12.7 months, p value=0.175) was found. NLR ≥4 had worse OS (8.2 vs 17.7 months, p value=0.0001). In multivariate analysis, BMI ≥30, bone metastases, NLR ≥4, performance status ≥2 and line of ICI ≥2 were independent factors for OS., Conclusions: Our data identified BMI and bone metastases as novel clinical biomarkers that were independently associated with ICI outcomes in mUC. External and prospective validation are warranted., Competing Interests: Competing interests: Nicholas Meti—Honoraria: Takeda, Novartis. Consulting: Takeda, Seagen, AstraZeneca, Pfizer. Srikala S Sridhar—Consulting: Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, BMS, Eisai, EMD Serono, Gilead, Ipsen, Janssen, Merck, Pfizer, Seagen; Research funding (Institution): Janssen, Seagen, EMD Serono. Rossanna C Pezo—Honoraria: Pfizer, Novartis, BMS, Merck, Sanofi, Gilead, AstraZeneca; Research funding (Institution): Merck, Novartis, Pfizer, Taiho, Jazz Pharmaceuticals, ZymeWorks, AstraZeneca. Cristiano Ferrario—Honoraria: Pfizer, Bayer, Novartis, Roche, Bayer, Knight therapeutics, AstraZeneca, Merck, Astellas Pharma; Consulting—Merck, Novartis, AstraZeneca, Roche; Research funding (Institution): Merck, Novartis, Pfizer, Lilly, ZymeWorks, AstraZeneca, Janssen Oncology, Bayer, Astellas Pharma, Roche, Sanofi, Seattle Genetics, Semonix Pharmaceuticals, Bicycle Therapeutics, Immunomedics. Susanna Cheng—Consulting: AstraZeneca, Merck. April A N Rose—Consulting: EMD Serono, Advanced accelerator applications/Novartis; Research funding (Personal): Canadian Institutes of Health Research CIHR, Canadian Cancer Society, Conquer Cancer Foundation, Jewish General Hospital Foundation, TransMedTech Institute, Canada Foundation of Innovation; Research Funding (Institution): AstraZeneca, Merck, Pfizer, Seattle Genetics; Employment: Family member Merck. Soumaya Labidi, Mengqi Li, Sonia V Del Rincon, Reeta Barua, Jamila Riromar, Di Maria Jiang, Nazanin Fallah-Rad, Adrian G Sacher: no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Human beings are constantly exposed to the radiations coming from the environment. This work assesses the radiological hazards of natural radioactivity in soil samples taken at four locations around the phosphate area in south Tunisia. Concentrations of primordial radionuclides were measured by gamma spectrometer using an HPGe detector. The overall mean values of 40K, 226Ra and 232Th concentrations were 264, 27 and 13 Bq kg-1, respectively. From the radioactivity measurements, radiation hazard indices specified by the United Nation Scientific Committee on the Effect of Atomic Radiation such as radium equivalent activity (Raeq), absorbed dose rates ($ {\dot{\text D}} $) and annual effective dose (AED) to the population for outdoor environment were determined. The mean values for the abovementioned parameters were 64 Bq kg-1, 33 nGy h-1 and 40 μSv y-1, respectively., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Recent advances in sequencing technologies have significantly increased our capability to acquire large amounts of genetic data. However, the clinical relevance of the generated data continues to be challenging particularly with the identification of Variants of Uncertain Significance (VUSs) whose pathogenicity remains unclear. In the current report, we aim to evaluate the clinical relevance and the pathogenicity of VUSs in DNA repair genes among Tunisian breast cancer families. Methods: A total of 67 unsolved breast cancer cases have been investigated. The pathogenicity of VUSs identified within 26 DNA repair genes was assessed using different in silico prediction tools including SIFT, PolyPhen2, Align-GVGD and VarSEAK. Effects on the 3D structure were evaluated using the stability predictor DynaMut and molecular dynamics simulation with NAMD. Family segregation analysis was also performed. Results: Among a total of 37 VUSs identified, 11 variants are likely deleterious affecting ATM, BLM, CHEK2, ERCC3, FANCC, FANCG, MSH2, PMS2 and RAD50 genes. The BLM variant, c.3254dupT, is novel and seems to be associated with increased risk of breast, endometrial and colon cancer. Moreover, c.6115G>A in ATM and c.592+3A>T in CHEK2 were of keen interest identified in families with multiple breast cancer cases and their familial cosegregation with disease has been also confirmed. In addition, functional in silico analyses revealed that the ATM variant may lead to protein immobilization and rigidification thus decreasing its activity. We have also shown that FANCC and FANCG variants may lead to protein destabilization and alteration of the structure compactness which may affect FANCC and FANCG protein activity. Conclusion: Our findings revealed that VUSs in DNA repair genes might be associated with increased cancer risk and highlight the need for variant reclassification for better disease management. This will help to improve the genetic diagnosis and therapeutic strategies of cancer patients not only in Tunisia but also in neighboring countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Boujemaa, Nouira, Jandoubi, Mejri, Bouaziz, Charfeddine, Ben Nasr, Labidi, El Benna, Berrazega, Rachdi, Daoud, Benna, Haddaoui, Abdelhak, Samir Boubaker, Boussen and Hamdi.)

Computerized segmentation of brain tumor based on magnetic resonance imaging (MRI) data presents an important challenging act in computer vision. In image segmentation, numerous studies have explored the feasibility and advantages of employing deep neural network methods to automatically detect and segment brain tumors depicting on MRI. For training the deeper neural network, the procedure usually requires extensive computational power and it is also very time-consuming due to the complexity and the gradient diffusion difficulty. In order to address and help solve this challenge, we in this study present an automatic approach for Glioblastoma brain tumor segmentation based on deep Residual Learning Network (ResNet) to get over the gradient problem of deep Convolutional Neural Networks (CNNs). Using the extra layers added to a deep neural network, ResNet algorithm can effectively improve the accuracy and the performance, which is useful in solving complex problems with a much rapid training process. An additional method is then proposed to fully automatically classify different brain tumor categories (necrosis, edema, and enhancing regions). Results confirm that the proposed fusion method (ResNet-SVM) has an increased classification results of accuracy (AC = 89.36%), specificity (SP = 92.52%) and precision (PR = 90.12%) using 260 MRI data for the training and 112 data used for testing and validation of Glioblastoma tumor cases. Compared to the state-of-the art methods, the proposed scheme provides a higher performance by identifying Glioblastoma tumor type.

Background and Purpose: We aimed to translate the Comprehensive Score of Financial Toxicity (COST) questionnaire into Arabic and to evaluate its reliability and validity. Methods: We applied the four-step translation method and conducted a pilot validation study over 179 medical oncology patients. Reliability was tested using the Cronbach alpha coefficient and test-retest stability. Validity was tested using the correlation with Functional assessment of Cancer Therapy-General score (FACT-G), factorial analysis and the content validity index. Results: Questionnaire showed high internal consistency and test retest reliability; Cronbach alpha coefficient was 0.77 and Pearson stability coefficient was 0.8. Convergent validity evaluation showed a statistically significant moderate correlation with the FACT-G ( r = .42, p =.047). Content validly index was 0.93. Conclusions: The Arabic version of COST questionnaire, was a valid and reliable tool that could be used in clinical practice by healthcare providers to evaluate financial toxicity in Arab speaking cancer patients., (© Copyright 2022 Springer Publishing Company, LLC.)

Breast cancer has different epidemio-clinical characteristics in Middle East and North-African populations compared to those reported in the Western countries. The aim of this study is to analyze the epidemiological and clinico-pathological features of breast cancer in Tunisia and to determine prognostic factors with special interest to family history, Ki-67 proliferation index and comorbidity. We retrospectively reviewed epidemiological and clinico-pathological data from patients' medical records, treated in the Medical Oncology Department at Abderrahmane Mami Hospital, in the period 2011-2015. Data has been collected on 602 breast cancer patients and analyzed using SPSS software V.23.0. Our study showed high fractions of young breast cancer patients and cases with dense breasts. The most prevalent comorbidities observed in the studied cohort were cardiovascular diseases and diabetes. Familial breast cancer was found in 23.3% of cases and was associated with younger age at diagnosis (p<0.001) and advanced stage (p = 0.015). Ki-67 index >20% was significantly associated with early age at diagnosis, lymph node involvement (p = 0.002), advanced tumor grade (p<0.001) and high risk of relapse (p = 0.007). Ki-67 cut-off 30% predicted survival in luminal cases. Survival was worse in patients with triple negative breast cancer compared to non-triple negative breast cancer, inflammatory breast cancer compared to non-inflammatory breast cancer, moderately to poorly differentiated tumors compared to well-differentiated tumors and with positive lymph nodes compared to pN0 (p<0.05). Our study showed new insights into epidemiological and clinico-pathological characteristics of breast cancer that are not well explored in Tunisian population. Considering our findings along with the implementation of electronic health record system may improve patient health care quality and disease management., Competing Interests: The authors have declared that no competing interests exist.

A full 3D analysis of the hierarchical porosity in Coscinodiscus sp. diatom structures was carried out by using a multiscale approach that combines three advanced volumetric imaging techniques with resolutions and fields of view covering all the porous characteristics of such complex architectures: electron tomography, "slice and view" approach that uses a dual-beam microscope (FIB-SEM), and array tomography consisting of serial imaging of ultrathin specimen sections. This multiscale approach allowed the whole porosity network to be quantified and provided an unprecedented structural insight into these natural nanostructured materials with internal organization ranging from micrometer to nanometer. The analysed species is made of several nested layers with different pore sizes, shapes and connectivities and characterized by the presence of interconnected pores structured in various ways. The first evidence of the presence of a nanometric porosity made of ellipsoidal pores in the siliceous diatom frustules is also provided., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: Tumor-infiltrating lymphocytes represent a pivotal component of the host anti-tumor response. Thus, they considerably influence the evolution of cancers including non-small cell lung carcinomas. Even if, this important role is consensual, many discordant results are published in the literature about the prognostic role of the different populations of tumor-infiltrating lymphocytes. The aim of our work was to evaluate the prognostic impact of CD8+, CD4+, and forkhead box protein P3+ lymphocytes in the tumor microenvironment of non-small cell lung carcinomas., Methods: We conducted a retrospective descriptive study, which included non-small cell lung carcinomas diagnosed in the department of pathology and followed in the medical oncology department of the same hospital between 2011 and 2015. Tumor-infiltrating lymphocytes were analyzed by the immunohistochemical method for forkhead box protein P3, CD4, and CD8. Intratumoral and stromal-labeled lymphocytes were quantified by manual counting at high magnification (×400). Forkhead box protein P3+/CD8+, forkhead box protein P3+/CD4+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of tumor-infiltrating lymphocytes was assessed in respect of overall survival, recurrence-free survival, and relapse-free survival., Results: Thirty-nine patients were included. The mean age of patients was 59.6 years. A complete surgical resection ( p  = 0.009), and a CD8/CD4 ratio ( p  = 0.008) were prognostic factors for overall survival. Complete surgical resection ( p  = 0.003), the forkhead box protein P3/CD8 ( p  = 0.005), and forkhead box protein P3/CD4 ( p  = 0.037) ratios were prognostic factors for recurrence-free survival. The CD8+ tumor-infiltrating lymphocytes rate ( p  = 0.037) was a prognostic factor for relapse-free survival with a threshold of 67.8/high power field. Microscopic subtype ( p  = 0.037) was a prognostic factor for relapse-free survival when only adenocarcinoma and squamous cell carcinoma were considered. In multivariate analysis, age ( p  = 0.004) and a CD8/CD4 ratio ( p  = 0.016) were independent predictors of overall survival., Conclusion: Despite the limitations of our study, our results confirm the prognostic value of tumor-infiltrating lymphocytes in non-small cell lung carcinomas and the importance of the combined quantification of their different subpopulations.

Introduction: The complexity of histopathological images remains a challenging issue in cancer diagnosis. A pathologist analyses immunohistochemical images to detect a colour-based stain, which is brown for positive nuclei with different intensities and blue for negative nuclei. Several issues emerge during the eyeballing tissue slide analysis, such as colour variations caused by stain inhomogeneity, non-uniform illumination, irregular cell shapes, and overlapping cell nuclei. To overcome those problems, an automated computer-aided diagnosis system is proposed to segment and quantify digestive neuroendocrine tumours., Material and Methods: We present a novel pre-processing approach based on colour space assessment. A criterion called pertinence degree is introduced to select the appropriate colour channel, followed by contrast enhancement. Subsequently, the adaptive local threshold technique that uses the modified Laplacian filter is applied to minimize the implementation complexity, highlight edges, and emphasize intensity variation between cells across the slide. Finally, the improved watershed algorithm based on the concave vertex graph is applied for cell separation., Results: The performance of the algorithms for nucleus segmentation is evaluated according to both the object-level and pixel-level criteria. Our approach increases segmentation accuracy, with the F1-score equal to 0.986. There is significant agreement between the applied approach and the expert's ground truth segmentation., Conclusions: The proposed method outperformed the state-of-the-art techniques based on recall, precision, the F1-score, and the Dice coefficient.

This study proposes a new predictive segmentation method for liver tumors detection using computed tomography (CT) liver images. In the medical imaging field, the exact localization of metastasis lesions after acquisition faces persistent problems both for diagnostic aid and treatment effectiveness. Therefore, the improvement in the diagnostic process is substantially crucial in order to increase the success chance of the management and the therapeutic follow-up. The proposed procedure highlights a computerized approach based on an encoder-decoder structure in order to provide volumetric analysis of pathologic tumors. Specifically, we developed an automatic algorithm for the liver tumors defect segmentation through the Seg-Net and U-Net architectures from metastasis CT images. In this study, we collected a dataset of 200 pathologically confirmed metastasis cancer cases. A total of 8,297 CT image slices of these cases were used developing and optimizing the proposed segmentation architecture. The model was trained and validated using 170 and 30 cases or 85% and 15% of the CT image data, respectively. Study results demonstrate the strength of the proposed approach that reveals the superlative segmentation performance as evaluated using following indices including F1-score = 0.9573, Recall = 0.9520, IOU = 0.9654, Binary cross entropy = 0.0032 and p-value <0.05, respectively. In comparison to state-of-the-art techniques, the proposed method yields a higher precision rate by specifying metastasis tumor position.

Background: Breast cancer is the world's most common cancer among women. It is becoming an increasingly urgent problem in low- and middle-income countries (LMICs) where a large fraction of women is diagnosed with advanced-stage disease and have no access to treatment or basic palliative care. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1 /2 genes. Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations., Methods: A total of 354 patients diagnosed with breast and ovarian cancers, including 5 male breast cancer cases, have been investigated for BRCA1/2 mutations using traditional and/or next generation sequencing technologies. Clinicopathological signatures associated with BRCA mutations have also been investigated., Results: In the current study, 16 distinct mutations were detected: 10 in BRCA1 and 6 in BRCA2 , of which 11 are described for the first time in Tunisia including 3 variations that have not been reported previously in public databases namely BRCA1 &#95;c.915T>A; BRCA2 &#95;c.-227-?&#95;7805+? and BRCA2 &#95;c.249delG. Early age at onset, family history of ovarian cancer and high tumor grade were significantly associated with BRCA status. BRCA1 carriers were more likely to be triple negative breast cancer compared to BRCA2 carriers. A relatively high frequency of contralateral breast cancer and ovarian cancer occurrence was observed among BRCA carriers and was more frequent in patients carrying BRCA1 mutations., Conclusion: Our study provides new insights into breast and ovarian cancer genetic landscape in the under-represented North African populations. The prevalence assessment of novel and recurrent BRCA1/2 pathogenic mutations will enhance the use of personalized treatment and precise screening strategies by both affected and unaffected North African cancer cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hamdi, Mighri, Boujemaa, Mejri, Ben Nasr, Ben Rekaya, Messaoud, Bouaziz, Berrazega, Rachdi, Jaidane, Daoud, Zribi, Ayari, El Benna, Labidi, Ben Hassouna, Haddaoui, Rahal, Benna, Mrad, Ben Ahmed, Boussen, Boubaker and Abdelhak.)

BRCA1 and BRCA2 are the most commonly mutated breast cancer susceptibility genes that convey a high risk of breast and ovarian cancer. Most BRCA1 or BRCA2 mutation carriers have inherited a single heterozygous mutation. In recent years, very rare cases with biallelic or trans double heterozygous mutations on BRCA1 and or BRCA2 have been identified and seem to be associated with distinctive phenotypes. Given that this genotype-phenotype correlation in cancer predisposing hereditary conditions is of relevance for oncological prevention and genetic testing, it is important to investigate these rare BRCA genotypes for better clinical management of BRCA mutation carriers. Here we present the first report on Cis double heterozygosity ( Cis DH) on BRCA2 gene identified using Whole exome sequencing (WES) in a Tunisian family with two BRCA2 mutations namely: c.632-1G>A and c.1310&#95;1313DelAAGA that are both reported as pathogenic in ClinVar database. Subsequent analysis in 300 high-risk Tunisian breast cancer families detected this Cis double heterozygous genotype in 8 additional individuals belonging to 5 families from the same geographic origin suggesting a founder effect. Moreover, the observed Cis DH seems to be associated with an early age of onset (mean age = 35.33 years) and severe phenotype of the disease with high breast cancer grade and multiple cancer cases in the family. The identification of unusual BRCA genotypes in this Tunisian cohort highlights the importance of performing genetic studies in under-investigated populations. This will also potentially help avoiding erroneous classifications of genetic variants in African population and therefore avoiding clinical misdiagnosis of BRCA related cancers. Our findings will also have an impact on the genetic testing and the clinical management of North African breast cancer patients as well as patients from different other ethnic groups in regard to several emerging target therapies such as PARP inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hamdi, Boujemaa, Mighri, Mejri, Jaidane, Ben Nasr, Bouaziz, Hassouna, Zribi, Berrazaga, Rachdi, Daoud, El Benna, Labidi, Haddaoui, Rahal, Benna, Boussen, Abdelhak and Boubaker.)

Background: Cancer care-related out-of-pocket expenses and financial toxicity (FT) are a rising burden for patients. We aimed to evaluate patient-reported FT and to identify relevant correlates within a Tunisian population., Methods: We conducted a survey using the 11-item Comprehensive Score for Financial Toxicity (COST) that could range from 0 = high to 44 = low. FT was grade 0 if ≥ 26, grade 1 = (14-25), grade 2 = (1-13), and grade 3 = 0. Scores were collected along with data regarding patient medical/social features and out-of-pocket expenses. Univariate and multivariate analyses were performed to identify factors associated with higher financial burden., Results: Among the 179 participants, median COST score was 20.8 (Q1 17-Q3 24), with 80.4% of patients experiencing financial toxicity: grade 0 = 20%, grade 1 = 68.4%, grade 2 = 11.7%, grade 3 = 0%. Most patients (66.5%) used to work before cancer and 44.7% reported ceasing work because of cancer. The time to go to the hospital was > 30 min in 66.5% of cases. Unemployment, time to hospital > 30 min, ceasing work because of cancer, and expenses on non-chemotherapy drugs exceeding 70 dinars (25 US dollars) were mostly associated with higher FT on univariate analysis. Distance to hospital and ceasing work because of cancer were the single most significant factors in multivariate analysis., Conclusions: Losing work due to cancer and unequal distribution of health care particularly in cities with long travel times to the nearest hospital are the main sources of financial distress.

Background: Prognostic factors are crucial to guide patient's selection through therapeutic decisions and outcome prediction., Aim: To investigate prognostic factors associated with improved survival in stage III non-small cell lung cancer., Patients and Methods: We retrospectively reviewed clinical data of 88 stage III non-small cell lung cancer patients treated between 2010-2017. Multidisciplinary evaluation prior to therapy onset was mandatory. Univariate analyses and multivariate logistic regression were performed to identify factors associated with survival., Results: Median follow-up was 28 months, 56% of patients experienced recurrence. Median overall survival (OS) was 19 months. On univariable analysis, improved OS correlated with younger age (p = 0.011), better performance score (ECOG PS < 2) (p < 0.01), absence of weight loss (p = 0.019) and smaller tumor size (≤ 7 cm) (p = 0.005). OS was improved in patients receiving therapy planned by multidisciplinary meeting compared with those who did not (p < 0.01), in those with resected tumors (p = 0.001), responding to therapy (neoadjuvant chemotherapy (p = 0.034) and concurrent chemoradiation (p = 0.001), as well as those with lower neutrophil-lymphocyte ratio (p = 0.026) and lower platelet-lymphocyte ratio (p = 0.003). Postoperative adjuvant therapy increased OS (64 vs 24, p = 0.025). Longer recurrence-free interval, locoregional failure and better perfomance status at recurrence were good prognostic factors for OS. Multivariate analysis showed that only upfront surgery followed by adjuvant therapy (hazard ratio (HR) = 0.61; 95% confidence interval (CI) 0.38-0.96; p = 0.034), adherence to multidisciplinary team decision (HR = 0.26; 95% CI 0.15-0.47; p < 0.01) and tumor size > 7 cm (HR = 2.31; 95% CI 1.29-4.13; p = 0.005) were independent prognostic factors affecting OS., Conclusions: Optimal therapeutic strategy and adherence to the decision provided by the multidisciplinary evaluation of patients played an important role in stage III non-small cell lung cancer outcome.

Vertigo is a common sign related to a problem with the brain or vestibular system. Detection of ocular nystagmus can be a support indicator to distinguish different vestibular disorders. In order to get reliable and accurate real time measurements from nystagmus response, video-oculography (VOG) plays an important role in the daily clinical examination. However, vestibular diseases present a large diversity in their characteristics that leads to many complications for usual analysis. In this paper, we propose a novel automated approach to achieve both selection and classification of nystagmus parameters using four tests and a pupil tracking procedure in order to give reliable evaluation and standardized indicators of frequent vestibular dysfunction that will assist clinicians in their diagnoses. Indeed, traditional tests (head impulse, caloric, kinetic and saccadic tests) are applied to obtain clinical parameters that highlight the type of vertigo (peripheral or central vertigo). Then, a pupil tracking method is used to extract temporal and frequency nystagmus features in caloric and kinetic sequences. Finally, all extracted features from the tests are reduced according to their high characterization degree by linear discriminant analysis, and classified into three vestibular disorders and normal cases using sparse representation. The proposed methodology is tested on a database containing 90 vertiginous subjects affected by vestibular Neuritis, Meniere's disease and Migraines. The presented technique highly reduces labor-intensive workloads of clinicians by producing the discriminant features for each vestibular disease which will significantly speed up the vertigo diagnosis and provides possibility for fully computerized vestibular disorder evaluation.

Background: The coronavirus disease 2019 (COVID-19) pandemic presents serious challenges to cancer care because of the associated risks from the infection itself and the disruption of care delivery. Therefore, many professional societies have published recommendations to help manage patients with cancer during the current pandemic. The objective of our study is to assess the national responses of Middle East North Africa (MENA) countries in terms of publishing relevant guidelines and analyse various components of these guidelines., Methods: A survey based on the preliminary review of the literature regarding cancer care adaptations has been developed and then completed by a group of oncologists from the following Arab countries affected by the pandemic: Algeria, Egypt, Iraq, Jordan, Kuwait, Lebanon, Morocco, Oman, Saudi Arabia, Syria, Tunisia, United Arab Emirates and Yemen. The survey inquired about COVID-19 cases, national recommendations regarding general measures of COVID-19 prevention and patient care in oncology as well as their implementation about cancer care adaptations during the pandemic., Results: Analysis of the COVID-19 pandemic-related guidelines revealed at least 30 specific recommendations that we categorised into seven essential components. All included countries had national guidelines except one country. Estimated full compliances with all specific category recommendations ranged from 30% to 69% and partial compliance ranged from 23% to 61%., Conclusion: There is a very good response and preparedness in the Arab Middle East and North Africa region surveyed. However, there are inconsistencies in the various components of the guidelines across the region, which reflects the evolving status of the pandemic in each country as well as the lack of clear evidence-based guidelines for many of the issues in question. There is a need for a clear framework on essential components that should be included in these guidelines to assure providing the best guidance to the oncology community., Competing Interests: Zineb Benbrahim received educational grants from Novartis, MSD, AstraZeneca. Humaid O Al Shamsi received research support from ROCHE. AR Jazieh received research funds from MSD., (© the authors; licensee ecancermedicalscience.)

Hereditary breast cancer accounts for 5-10% of all breast cancer cases. So far, known genetic risk factors account for only 50% of the breast cancer genetic component and almost a quarter of hereditary cases are carriers of pathogenic mutations in BRCA1/2 genes. Hence, the genetic basis for a significant fraction of familial cases remains unsolved. This missing heritability may be explained in part by Copy Number Variations (CNVs). We herein aimed to evaluate the contribution of CNVs to hereditary breast cancer in Tunisia. Whole exome sequencing was performed for 9 BRCA negative cases with a strong family history of breast cancer and 10 matched controls. CNVs were called using the ExomeDepth R-package and investigated by pathway analysis and web-based bioinformatic tools. Overall, 483 CNVs have been identified in breast cancer patients. Rare CNVs affecting cancer genes were detected, of special interest were those disrupting APC2, POU5F1, DOCK8, KANSL1, TMTC3 and the mismatch repair gene PMS2. In addition, common CNVs known to be associated with breast cancer risk have also been identified including CNVs on APOBECA/B, UGT2B17 and GSTT1 genes. Whereas those disrupting SULT1A1 and UGT2B15 seem to correlate with good clinical response to tamoxifen. Our study revealed new insights regarding CNVs and breast cancer risk in the Tunisian population. These findings suggest that rare and common CNVs may contribute to disease susceptibility. Those affecting mismatch repair genes are of interest and require additional attention since it may help to select candidates for immunotherapy leading to better outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: Deleterious mutations on BRCA1/2 genes are known to confer high risk of developing breast and ovarian cancers. The identification of these mutations not only helped in selecting high risk individuals that need appropriate prevention approaches but also led to the development of the PARP-inhibitors targeted therapy. This study aims to assess the prevalence of the most frequent BRCA1 mutation in Tunisia, c.211dupA, and provide evidence of its common origin as well as its clinicopathological characteristics. We also aimed to identify additional actionable variants using classical and next generation sequencing technologies (NGS) which would allow to implement cost-effective genetic testing in limited resource countries., Patients and Methods: Using sanger sequencing, 112 breast cancer families were screened for c.211dupA. A set of patients that do not carry this mutation were investigated using NGS. Haplotype analysis was performed to assess the founder effect and to estimate the age of this mutation. Correlations between genetic and clinical data were also performed., Results: The c.211dupA mutation was identified in 8 carriers and a novel private BRCA1 mutation, c.2418dupA, was identified in one carrier. Both mutations are likely specific to North-Eastern Tunisia. Haplotype analysis supported the founder effect of c.211dupA and showed its recent origin. Phenotype-genotype correlation showed that both BRCA1 mutations seem to be associated with a severe phenotype. Whole Exome Sequencing (WES) analysis of a BRCA negative family revealed a Variant of Unknown Significance, c.3647C > G on RAD50 . Molecular modeling showed that this variant could be classified as deleterious as it is responsible for destabilizing the RAD50 protein structure. Variant prioritization and pathway analysis of the WES data showed additional interesting candidate genes including MITF and ANKS6., Conclusion: We recommend the prioritization of BRCA1 -c.211dupA screening in high risk breast cancer families originating from the North-East of Tunisia. We also highlighted the importance of NGS in detecting novel mutations, such as RAD50- c.3647C > G. In addition, we strongly recommend using data from different ethnic groups to review the pathogenicity of this variant and reconsider its classification in ClinVar., (Copyright © 2020 Mighri, Hamdi, Boujemaa, Othman, Ben Nasr, El Benna, Mejri, Labidi, Ayari, Jaidene, Bouaziz, Ben Rekaya, M’rad, Haddaoui, Rahal, Boussen, Boubaker and Abdelhak.)

Whereas the role of arbuscular mycorrhizal fungi (AMF) in plant growth improvement has been well described in agroecosystems, little is known about the effect of environmental factors on AMF root colonization status of barley, the fourth most important cereal crop all over the world. In order to understand the influence of environmental factors, such as climatic and soil physico-chemical properties, on the spontaneous mycorrhizal ability of barley (Hordeum vulgare L.), a field investigation was conducted in 31 different sites in sub-humid, upper and middle semi-arid areas of Northern Tunisia. Mycorrhizal root colonization of H. vulgare varied considerably among sites. Principal component analysis showed that barley mycorrhization is influenced by both climatic and edaphic factors. A partial least square structural equation modelling (PLS-SEM) revealed that 39% (R²) of the total variation in AMF mycorrhizal rate of barley roots was mainly explained by chemical soil properties and climatic characteristics. Whereas barley root mycorrhizal rates were inversely correlated with soil organic nitrogen (ON), available phosphorus amounts (P), altitude (Z), average annual rainfall (AAR), they were directly correlated with soil pH and temperature. Our results indicated that AMF root colonization of barley was strongly related to climatic characteristics than chemical soil properties. The current study highlights the importance of the PLS-SEM to understand the interactions between climate, soil properties and AMF symbiosis of barley in field conditions., Competing Interests: The authors have declared that no competing interests exist.

This study aims to develop an Automatic Brain Dose Estimation (ABDE) methodology for head computed tomography examinations. The ABDE is to be applied first to an anthropomorphic Alderson phantom to obtain a Correction factor (Cf) between the ABDE and the direct absorbed brain dose using dosemeters positioned within the anthropomorphic phantom. Then, in order to estimate the correct brain dose for patient, the Cf was multiplied by the mean ABDE values for each patient. Results were compared to those registered with a mathematical simulation phantom using CT-Expo V 2.4 software. Results showed no significant difference between the correct ABDE values and the CT-Expo values with a mean percent difference of 2.54 ± 0.01%. In conclusion, ABDE yields a correct estimation of brain dose, taking into account the size and attenuation of the irradiated region. Thus, it is clinically recommended for accurate patient brain dose assessment., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: We aimed to explore the use of complementary and alternative medicine (CAM) and to identify their side effects, when used in cancer patients. We also assessed the communication of the patients and families with the oncologist about this issue., Methods: A cross-sectional survey of 120 adult patients treated for cancer in our medical oncology department between January and April 2019, using an anonymous questionnaire to assess complementary and alternative medicine use., Results: One hundred twenty patients participated in the survey, among them 102 used CAM (85%). A majority of users were female patients (n=72, 70.6%), and mean age was 52.4 years±11.6. Patients had breast cancer in 48% of cases. Wild herbs were the most commonly used alternative therapy (67.7%), particularly Ephedra foeminea (Alanda) in 52% of cases. Patients' families incited them to use CAM in 64.7% of cases. Internet and social network (Facebook) were the major sources of information on CAM (79.4%), followed by family and friends (72.5%). Fourteen patients (13.7%) reported nausea and vomiting secondary to CAM use. We reported disruption of liver function in 9.8% of cases, and renal failure in 1.96%, with fatal issue in one patient using Ephedra. Nineteen patients (18.6%) informed their oncologist about the alternative therapy they received., Conclusion: The oncologist has to explore the use of alternative therapies with their patients. Communication about CAM should be a part of cancer care. It may protect patients from some dangerous side effects and improve efficacy of conventional therapy., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objective: We evaluated the risk factors of inflammatory breast cancer (IBC) compared to non-IBC and according to histological subtype., Methods: Cases of IBC (n = 160) and controls of non-IBC (n = 580) were collected from the cohort of breast cancer patients treated in two oncology centers matched based on age at cohort entry. Data about breast cancer risk factors were collected. We evaluated correlation and ORs using conditional logistic regression analysis for each case group versus the control group. We also evaluated those factors in three further subgroups: luminal (HR+, HER2-), HER2-overexpressing (HER2+, HR-), and triple-negative (TN) patients., Results: Long duration of breastfeeding of ≥12 months (OR = 4.64, 95% CI 2.97-7.26), body mass index ≤25 (OR = 2.48, 95% CI 1.71-3.58), and use of oral contraceptives (OR = 2.48, 95% CI 1.62-3.84) were the most significant risk factors in favor of IBC compared to non-IBC. There was no impact of contraceptives use in the luminal subgroup and no impact of long duration of breastfeeding in the TN subgroup. The role of socioeconomic and educational levels was unclear. Age at menarche, age at first pregnancy, and age at menopause were nonsignificant risk factors of IBC., Conclusion: Reproductive risk factors were distinct in IBC patients reflecting the clinical entity of IBC., (© 2020 S. Karger AG, Basel.)

Introduction: There is growing evidence that formative assessment is valuable tool in enhancing learning. Integrating formative assessment into post graduate students can be challenging., Aim: Authors aimed in this study to describe an ongoing formative assessment activity in post graduates. We reported resident's performance and satisfaction., Methods: Authors performed an exploratory study over a 3-year period. Twenty five oncology residents participated. The first phase was test preparation by senior oncologists, according to residency curricula then taking the test by a small group of residents with an immediate feedback. The third phase was distribution of a survey each 6 months evaluating resident's perception of the testing., Results: Twenty two tests were taken by 17 medical oncology, 2 surgical oncology and 4 radiation therapy residents.  At the first test, median scores was 51/100 [30%-72%] with a mean of 53/100. Individual scores of each resident improved with time, becoming 68/100 (t(16)=3.172, p<0.02) with a mean of 64/100 and decrease between student's scores. All the students rated the correction session with a 5. The majority reported that the test reached their expectations (73% rated4-5), and considered it, as having an impact on their daily practice (77% rated4-5). Residents also considered the test as highly difficult (80% rated4-5)., Conclusion: Ongoing formative assessment showed improvement in overall knowledge of residents with high level of satisfaction.

The activity concentrations of naturally occurring and anthropogenic radionuclides in agriculture soils as well as in several food products at four locations within the phosphate area of South Tunisia were investigated. Soil-to-plant transfer factors as well as feed-to-animal products transfer coefficients were determined for the first time for the region. Activity concentrations of 40 K, 210 Pb, 226 Ra, 228 Ra and 137 Cs in soils of agriculture fields were lower than worldwide average values. The soil-to-plant transfer factors (TFs) for 40 K in leafy vegetables were higher than those in fruit vegetables. Soil-to-grass transfer factor (F v ) values were in the following order: 40 K > 210 Pb > 226 Ra. The grass-to-milk transfer coefficient (F m ) values for 40 K and 210 Pb ranged between 2 × 10 -3 and 4 × 10 -3 (day L -1 ). The concentration ratios for the animal products (CR milk-feed , CR meat-feed and CR egg-feed ) varied in the ranges of 2 × 10 -2 -4 × 10 -2 L kg -1 , 1 × 10 -2 -2 × 10 -1 (L kg -1 ) and 5 × 10 -2 -1 (L kg -1 )for 40 K, 210 Pb and 226 Ra, respectively. Transfer parameters determined in the present study were compared with those reported in International Atomic Energy Agency reports and other published values. The absorbed gamma dose rate in air and the external hazard index associated with these natural radionuclides were computed to assess the radiation hazard of radioactivity in this region, and the results indicated that these areas are within set safety limits.

The activity concentration of natural and anthropogenic radionuclides was determined in different vegetable samples, and foods derived from animal origin, from different locations in the four cities of Southern Tunisia, where large-scale phosphate industries are operating. The aim of the studies was to establish a baseline database on radionuclide concentration in food materials and to evaluate the radiation dose to the general population due to its ingestion through the food chain. The activity concentrations of 40K, 210Pb, 226Ra, 228Ra and 137Cs was determined by gamma spectrometry using a HPGe detector, and from the measured activity concentrations, the doses were estimated using the dose coefficients given by the ICRP. The dose due to intake of radionuclides through mineral water was also determined. The total annual effective doses were found to be 2.2, 1.4, and 0.7 mSv y-1 for 1 y, 5-15 y and adult (>17 y) age groups, respectively. Among the radionuclides studied, 210Po was the highest contributor to the total dose, followed by 210Pb., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking., Methods: A whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein-protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk., Results: Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein-protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6., Conclusions: In this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific.

The purpose of this study is to assess dose for radiosensitive organs and image quality in head and chest computed tomography (CT) examinations. Our focus was in the brain, eye lens and lung organs using two protocols; one protocol with fixed mAs and filtered back projection (FBP) and another with tube current modulation (TCM) and sinogram affirmed iterative reconstruction (SAFIRE). Measurements were performed on a 128-slice CT scanner by placing thermoluminescent dosimeters (TLDs) in an anthropomorphic adult phantom. Results were compared to a CT-Expo software. Objective image quality was assessed in terms of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). SPSS software was used for data analyses. Results showed that, using TCM, doses were reduced by 22.84%-25.06% for brain, by 21.82%-23.48% for eye lens and by 54%-53.22% for lung with TLD and CT-Expo respectively. The increased SNR and CNR values achieved for scans performed with TCM combined with iterative reconstruction techniques were 38.68%-58.81% and 38.91%-43.60% respectively. We conclude that, using TCM, a significant mean organ dose reduction is achieved for brain, eye lens and lung organs. Then, combined with iterative reconstruction, image quality was well maintained in terms of SNR and CNR. Thus it is highly recommended in clinical practice optimization in head and chest CT examinations.

Background: We aimed to describe clinico-pathological characteristics and differences between right-sided (RCC) and left-sided colon cancer (LCC) in Tunisian population. We also analyzed outcome to determine whether location is of prognostic significance., Methods: Clinico-pathological characteristics and Kaplan Meier survival were compared between two groups of LCC [150] and RCC [53] patients with stage II and III adenocarcinoma treated with curative intent between 2003-2014., Results: RCC patients were significantly more likely to be female, (56.6% vs. 39.3%, P=0.029) and to have undifferentiated tumor (87.1% vs. 8.4%, P=0.014), then LCC. After a median follow up of 49 months, 5-year overall survival (OS) was significantly worse in RCC vs. LCC [42% vs. 78%; hazard ratio (HR) =2.07; 95% CI: 1.05-4.09; P=0.03], no difference in relapse free survival (RFS) was observed. Median time to relapse was significantly shorter in RCC (15 months) vs. LCC (24 months), P=0.005. Tumor location significantly impacted survival in stage III, 5-year OS was 45% in RCC, and 63% in LCC, (HR =2.28; 95% CI: 1.01-5.24; P=0.04), there was no impact of tumor location in stage II, (HR =1.94; 95% CI: 0.54-6.93; P=0.29)., Conclusions: Prognostic impact of tumor location should be considered as a stratification factor in the future clinical trials., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Aim: We reported anatomo-clinical features of brain metastases (BMs) collected in a Tunisian medical oncology department., Patients & Methods: We retrospectively identified all cases of BM within a cohort of 7055 patients, treated for a histologically confirmed nonhematological cancer between 2000 and 2016. Data about age, sex and primary tumor were collected., Results: Incidence was 1.9% and mean age was 54 years with a 1.24 sex ratio. BMs were symptomatic in 73.7% of cases after a median time of 16 months. A total of 73.4% patients receiving local therapy, 88% by whole brain radiation therapy and 21.6% had a metastasectomy. Lung and breast cancers were the primary in 80% of the BM., Conclusion: BM showed trends of young with underestimated incidence.

Purpose: To report the annual hazard of relapse in stages II and III colorectal cancer (CRC) Tunisian patients treated with curative intent. We also aim to evaluate impact of oxaliplatine according to anatomo-clinical features., Methods: We collected data about clinico-pathological parameters of 331 CRCs. We analyzed annual hazard of recurrence (locoregional and/or distant) of the overall population and several subgroups: colon cancer vs rectal cancer and stage II vs stage III. We also analyzed impact of adjuvant oxaliplatine on recurrence within these subgroups., Results: Relapse rate was 38.1%, with a mean time to relapse of 27.6 months. We noted 23.8% local recurrence, 69.8% distant recurrence, and 6.4% both. We observed higher local relapse rate in rectal cancer (26.8 vs 3.2%) vs colon cancer (p = 0.004). Stage III had a higher metastatic relapse rate vs stage II (31.6 vs 20.8%, p = 0.043). Annual hazard of recurrence for the overall population showed two peaks: [1-2] year-interval by 10.1% and [3-4] year-interval by 11.3%. Stage III showed significantly higher and earlier recurrence hazard peak compared to stage II (16.3 vs 8.1% in [1-2] year-interval). Oxaliplatine significantly improved annual hazard of recurrence in each year-interval from year 1-4, in colon cancer and in stage III but without impact in rectal cancer and stage II., Conclusion: Extended follow-up to 4 years should be considered in Tunisian population. Impact of oxaliplatine showed same features to reported occidental series.

A new case of epithelioid hemangioendothelioma is reported to have occurred to a 67-year-old patient who consulted for right-sided chest pain. The work-up showed multiple right pulmonary lesions associated with bilateral moderate pleural effusion and left-sided pleural thickening and three hypodense nodules in the right lobe of the liver, peritoneal thickening, ascites, and multiple vertebral lytic lesions. The diagnosis of an epithelioid hemangioendothelioma was concluded through a histological examination of a computed tomography scan guided biopsy of the liver. The patient received a primary mono-chemotherapy with Adriamycin (75 mg/m 2 every three weeks) and intravenous bisphosphonates without response and general status impairment. The patient died after 16 months of follow-up.

Aided phytostabilization using coal fly ashes (CFAs) is an interesting technique to clean-up polluted soils and valorizing industrial wastes. In this context, our work aims to study the effect of two CFAs: silico-aluminous (CFA1) and sulfo-calcic (CFA2) ones, 10 years after their addition, on the phytostabilization of a highly Cd (cadmium), Pb (lead) and Zn (zinc) contaminated agricultural soil, with four forest tree species: Robinia pseudoacacia, Alnus glutinosa, Acer pseudoplatanus and Salix alba. To assess the effect of CFAs on trees, leaf fatty acid composition, malondialdehyde (MDA), oxidized and reduced glutathione contents ratio (GSSG: GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG), Peroxidase (PO) and Superoxide dismutase (SOD) activities were examined. Our results showed that CFA amendments decreased the CaCl 2- extractable fraction of Cd and Zn from the soil. However, no significant effect was observed on metal trace element (MTE) concentrations in leaves. Fatty acid percentages were only affected by the addition of sulfo-calcic CFA. The most affected species were A. glutinosa and R. pseudoacacia in which C16:0, C18:0 and C18:2 percentages increased significantly whereas the C18:3 decreased. The addition of sulfo-calcic CFA induced the antioxidant systems response in tree leaves. An increase of SOD and POD activities in leaves of trees planted on the CFA2-amended plot was recorded. Conversely, silico-aluminous CFA generated a reduction of lipid and DNA oxidation associated with the absence or low induction of anti-oxidative processes. Our study evidenced oxidative stress alleviation in tree leaves due to CFA amendments. MTE mobility in contaminated soil and their accumulation in leaves differed with the nature of CFA amendments and the selected tree species., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Human epidermal growth factor receptor-2 (HER2) is amplified in 25-30% of breast cancers and is associated with aggressive disease and poorer survival. Multiple anti-HER2 targeted therapies have dramatically changed management and outcome of this subgroup, both in adjuvant and metastatic settings. Despite the improvement of survival thanks to trastuzumab, unclear mechanisms of resistance occur, which has led to the development of new anti-HER2 therapies such as lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1). The optimal sequence of the available drugs is still not well established. All this progress raises the question of toxicity that need to be managed, especially with longer survival of patients. In this article, we review different anti-HER2 therapies used in HER2-positive m etastatic breast cancer.

Introduction: We aim to evaluate prevalence and characteristics of CTS in routine daily practice over a 5-year period, with a review of the literature., Methods: Patients treated with endocrine therapy (441) were retrospectively analyzed looking for CTS cases in aromatase inhibitors (219, 49.6%) and in tamoxifen (222, 50.3%) patients. We described patient's characteristics and CTS management. We also reviewed the literature reporting CTS in aromatase inhibitors clinical trials., Results: Six cases of CTS were diagnosed, all in patients on aromatase inhibitors given in the adjuvant setting. Prevalence was 2.7%. Median age was 54 years. CTS occurred under anastrozole in four cases and letrozole in two cases. One patient had severe intensity presentation. Median time to symptoms onset was 14 months, and resolution was obtained within 4 months after a nonsurgical treatment., Conclusion: Aromatase inhibitor-induced CTS is rare. It should be recognized and treated in order to avoid endocrine therapy discontinuation.

Objective: Implantable port thrombosis (IPT) in cancer patients is a relatively rare but severe complication. Several factors are reportedly associated with the occurrence of thrombosis. We aimed to describe the prevalence and the anatomoclinical features of IPT observed in cancer patients who were treated in a medical oncology department in Tunisia., Methods: A total of 600 cancer patients who had port implantation from January 2013 to December 2015 were retrospectively identified. Cases with symptomatic/incidental IPT (radiologically confirmed) were further identified. Epidemiological and anatomoclinical features were collected from patient records and the department database., Results: We observed that 33 of the 600 patients had IPT; thus, the prevalence was 5.5%. The median age was 57 years, and the gender ratio was 0.43. Overweight or obesity was observed in 73% of the patients. IPT occurred mainly in patients with breast (36.4%) and colorectal (33.3%) cancers, which were mostly nonmetastatic (79%). At least one identified classical thromboembolic risk factor was found in 13 patients (smoking in 9, tamoxifen in 2). IPT was symptomatic in 93% of the cases, occurring within an average time of 56 days. Implantable ports were removed because of infection in 2 cases and nonfunctionality in 3 cases. IPT treatment was based on low-molecular-weight heparins (94%) and antivitamin K (6%) for an average of 130 days. Four patients had post-therapy complications: one thrombosis recurrence and three infections., Conclusions: IPT cases in the 600 patients were observed to occur in obese nonmetastatic cancer patients within the first 3 months after IP implantation.

Background: Glioblastoma (GB) is the most common and lethal primary brain tumor in adults representing 25% of primary brain tumors in adults. The objective of our study was to report the epidemiologic, clinical and therapeutic features of GB in Tunisia., Methods: Our retrospective study included 41 patients with histologically confirmed GB treated between 2006 and 2012 at the medical oncology departments of Abderrahmane Mami hospital in Ariana and the military hospital in Tunis., Results: Median age was 54 years (13 to 72 years) and sex-ratio was 2.3. Karnofsky performance status (KPS) was <70% in 31.7% of cases, while Recursive partitioning analysis radiation therapy oncology group (RTOG-RPA) classification was III in 11 (26.8%), IV in 19 (46.3%), V in 10 (24.3%) and VI in 1 (2.4%) cases. Complete resection (CR) was achieved in 29 patients (70.7%), partial resection (PR) or tumor debulking in 5 patients (12.2%) and biopsy alone (BA) in 7 patients (17.1%). All patients received brain radiotherapy (RT) at a dose of 60 Gy combined with concurrent temozolomide (TMZ). Nineteen patients (46.3%) received adjuvant TMZ, 8 of them completed 6 cycles. Median overall survival (OS) was 12 months (2 to 56 months). Six, 12, 18 and 24-months OS rates were 84.6%, 57.6%, 35.4% and 20.7%, OS being correlated to age, KPS, RPA and quality of resection., Conclusion: Our retrospective study is the first African GB series. Despite it included predominantly poor prognosis patients with impaired neurocognitive function and adjuvant treatment discontinuation, our median OS was comparable to Stupp.

Arbuscular mycorrhizal fungus (AMF)-assisted phytoremediation could constitute an ecological and economic method in polluted soil rehabilitation programs. The aim of this work was to characterize the trace element (TE) phytoremediation potential of mycorrhizal Miscanthus × giganteus. To understand the mechanisms involved in arbuscular mycorrhizal symbiosis tolerance to TE toxicity, the fatty acid compositions and several stress oxidative biomarkers were compared in the roots and leaves of Miscanthus × giganteus cultivated under field conditions in either TE-contaminated or control soils. TEs were accumulated in greater amounts in roots, but the leaves were the organ most affected by TE contamination and were characterized by a strong decrease in fatty acid contents. TE-induced oxidative stress in leaves was confirmed by an increase in the lipid peroxidation biomarker malondialdehyde (MDA). TE contamination decreased the GSSG/GSH ratio in the leaves of exposed plants, while peroxidase (PO) and superoxide dismutase (SOD) activities were increased in leaves and in whole plants, respectively. AMF inoculation also increased root colonization in the presence of TE contamination. The mycorrhizal colonization determined a decrease in SOD activity in the whole plant and PO activities in leaves and induced a significant increase in the fatty acid content in leaves and a decrease in MDA formation in whole plants. These results suggested that mycorrhization is able to confer protection against oxidative stress induced by soil pollution. Our findings suggest that mycorrhizal inoculation could be used as a bioaugmentation technique, facilitating Miscanthus cultivation on highly TE-contaminated soil., (Copyright © 2015. Published by Elsevier B.V.)

The efficiency of two mycorrhizal bio-inoculants on the mineral uptake during the growth stages of a Mediterranean forage legume sulla (Hedysarum coronarium L.) was studied in the field on a highly calcareous soil. The first inoculum (Mm) was made up of a mixture of native arbuscular mycorrhizal fungi (AMF) isolated from calcareous soils: Septoglomus constrictum, Funneliformis geosporum, Glomus fuegianum, Rhizophagus irregularis and Glomus sp. The second was a commercial inoculum (Mi) containing one AMF species: R. irregularis. Both mycorrhizal inoculants increased total and arbuscular colonization of sulla roots. Inoculation with Mm showed a positive effect on sulla shoot dry weight (SDW) when compared to Mi and non-inoculated plants (control). Mineral contents (P, Mg, Mn, Fe) were higher in the shoots of sulla plants cultivated on mycorrhiza-inoculated plots compared to non-inoculated ones. This enhancement was observed during the flowering stage for P, Mg and Mn and during the rosette stage for Fe. An increase in P content of 50 % in plants inoculated with Mm compared to non-inoculated ones may be explained by the induction of root alkaline and acid phosphatase activities. Higher efficiency of native AMF species adapted to calcareous soils opens the way towards the development of mycorrhiza bio-fertilizers targeted to improve sustainable fertilization management in such soils.

Purpose: To analyze the profile of annual recurrence rate (ARR) of patients with early breast cancer (BC) in Tunisia., Patients and Methods: We classified 293 patients with histologically confirmed early BC relapsing after 1 year of follow up into three subgroups: hormone receptor (HR)+ 'HR' [estrogen receptor (ER)+ or progesterone receptor (PR)+ and human epidermal growth factor receptor 2 (HER2)-], triple negative 'TN' (ER-, PR- and HER2 score 0/1 or fluorescence in situ hybridization (FISH)/chromogenic in situ hybridization negative) and HER2 overexpression 'HER2' (HER2+). ARR was restricted to follow-up contribution of each specified time interval. The HR group was the reference group for comparison., Results: A higher proportion of patients who were up to 35 years old (18% versus 10%, p = 0.04), and patients with obesity (46% versus 26%, p = 0.045) was seen in the TN group. Median time to relapse (MTR) was shorter in TN and HER2 groups than in HR patients (20 and 29 months compared with 56 months, respectively, p < 0.001). In the HR group, the ARR was 22%, 16% and 10% at 3, 4 and 5 years respectively, becoming less than 3% at 7 years. In the TN group, 71% of patients relapsed during the first 2 years and the ARR declined rapidly to less than 1.5% after 4 years. In the HER2 group, the ARR peaked at 2 years (29%) and decreased significantly to 7% and 3% at 5 and 7 years respectively. Adjuvant trastuzumab delayed the MTR from 24 to 34 months (p = 0.022)., Conclusion: The relapse risk in Tunisian patients is higher in young women and patients with HER2+ and TN tumors. A long and close follow up is recommended for patients with HR and HER2. Conversely, we suggest that follow up in patients with TN could be spaced after 4 years (ARR being <1.5% after this period).

Background: Non-small cell lung cancer (NSCLC) is the most common histologic form, leading causes of cancer death among masculine population. Half of CNPC was metastatic at diagnosis., Aim: To report the epidemiologic, anatomoclinic profile, therapeutic protocols and results of a retrospective study of non-small cell lung cancer (NSCLC) initially metastatic., Methods: our retrospective study include patients with NSCLC histologically confirmed with inaugural metastasis collected from January 1999 to december 2012. We had analysed epidemiologic, anatomopathologic data (TNM 2009), therapeutic protocols and results in term of overall survival, median survival and event free survival., Results: 100 case of NSCLC have been collected, mea nage was 57 years (22 to 81) and sex -ratio was 4,6. The majority of cases (74%) had a good performance statut (PS ≤ 2). Pathologic analysis leads to 81 cases of adenocarcinoma (ADK), 16 epidermoid carcinoma. 34% was stager T4 and 31% N2. Metastasis was located to bone in 36 cases, pleural in 26 cases, controlateral lung 26 cases, adrenal gland 17 cases and brain in 13 cases. 82% of patients underwent polychemotherapy as first line of treatment based on regimens conteined platine with mean number of 4 cycles. We have observed 4% of complete response, 61 of partial response, 20% of stabilisation, and 15% of progression. A palliatif radiotherapy of bone or brain metastasis was performed in 38 % of cases. With a median follow-up of 71 months (12 to 130 months), mean survival was 11 months; overall survival (Kaplan-Meier) at 1, 3 and 5 years was respectively 44, 13 and 0 %., Conclusion: Despite therapeutic progress in management of NSCLC, the prognosis of metastatic forms still reserved with a poor mean survival reported in litterature (12 years) valideted in our study. This push us to improve research mainly since advent of targeted therapy wich still a promising way in the management of these tumors.

Aims: To analyze the medical literature concerning the results of the international randomized muticentric trials concerning therapeutic innovations, mainly targeted therapies in locally advanced and or metastatic renal cell cancer and to evaluate the benefit of these TT., Methods: We performed a review of publications that concerned this topic published from 2000 to 2014., Results: They concerned the large randomized trials have showed a benefit of the targeted therapies in the treatment of clear cell carcinomas in terms of progression-free survival., Conclusion: Advances in molecular biology have allowed the development of these targeted therapies that have all proved their role in the treatment of metastatic renal cell carcinoma., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)