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Intramedullary spinal cord metastasis (IMSC) from solid tumors is rare. In this report, we describe the case of a patient treated at our center for breast cancer with intramedullary spinal cord metastases without bone and brain metastases or meningitis. Management of the disease remains challenging even with recent advances in the treatment of metastatic breast cancer. Treatment options include surgery, radiotherapy and chemotherapy. The prognosis of these patients still very poor., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The PI3K protein is involved in the PI3K/AKT/mTOR pathway. Deregulation of this pathway through PIK3CA mutation is common in various tumors. The aim of this work is to identify hotspot mutation at exons 9 and 20 in Tunisian patients with sporadic or hereditary breast cancer., Methods: Hotspot mutations in exon 9 and exon 20 of the PIK3CA gene were identified by QPCR-High Resolution Melting followed by COLD-PCR and sequencing in 63 (42 sporadic cases and 21 hereditary cases) tumor tissues collected from Tunisian patient with breast cancer. MCF7, and BT20 breast cancer cell lines harboring the PIK3CA hotspot mutations E545K and H1047R in exon 9 and exon 20 respectively, were used as controls in HRM experiments., Results: PIK3CA hotspot mutations were detected in 66.7% (28 out of 42) of sporadic BC cases, and in 14.3% (3 out of 21) of hereditary BC. The E545K and the H1048Y were the most prevalent mutations identified in patients with sporadic and hereditary BC, whereas the H1047R hotspot mutation was not found in our patients. Statistical analysis showed that PIK3CA mutation associated with an aggressive behavior in patients with sporadic BC, while it's correlated with age, tumor stage and tumor size in the group patients with hereditary breast cancer., Conclusions: Our results showed a novel PIK3CA hotspot mutation in Tunisian breast cancer patients detected by HRM-COLD-PCR. Moreover, the absence of PIK3CA hotspot mutation associated with good prognosis.

Purpose: Radiation therapy with chemotherapy (CCR) is currently the gold standard treatment for nasopharyngeal carcinoma (NPC). Anatomical changes are mainly due to weight loss. Our prospective study aimed to evaluate the nutritional status and the quality of weight loss in our patients to adapt the subsequent nutritional management of patients during treatment for NPC., Patients and Methods: A prospective, single-center study of 27 patients with non-metastatic NPC treated in our oncology radiotherapy department between August 2020 and March 2021. Data from interrogation, physical examination, and bioelectrical impedancemetry (weight [W], body mass index [BMI], fat index [GI], fat mass [FM], and fat-free mass (FFM]) were collected at the beginning, the mid, and the end of treatment., Results: Weight loss from mid to end of treatment (median=-4kg [-9.4; -0.9]) was greater than that from baseline to mid-treatment (median=-2.9kg [-8.8; 1.8]) (P=0.016). Weight loss during the entire treatment was -6.2kg [-15.6; -2.5] (8.4%). The losses of FM were identical between the beginning-mid treatment and the mid-end treatment; they were respectively -1.4kg [-8.5; 4.2] and -1.4kg [-8.2; 7.8] (P=0.4). FFM losses between the mid- and the end of treatment (-2.5kg [-27.8; 0.5]) were greater than those between baseline and mid-treatment (-1.1kg [-7.1; 4.7]) (P=0.014). Median FFM loss during treatment was -3.6kg [-28.1; 2.6])., Conclusion: The results of our study show that weight loss during CCR for NPC is complex and is not just about loss but about a disruption of body composition. Regular follow-ups by nutritionists are required to prevent denutrition during treatment., (Copyright © 2023 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: Male breast cancer (MBC) is a rare malignancy presenting only 1% of all breast cancer. The purpose of this study was to analyze clinical and pathological prognostic factors of MBC., Methods: This is a retrospective study including 32 men diagnosed and treated for a primary breast cancer at the department of medical oncology in Sfax between 2005 and 2020., Results: The incidence of MBC was 1.3%. The median age of our patients was 55 years (range: 29-85 years). The average tumor size of 3.9 cm. Lymph nodes involvement was present in 18 cases (56.2%) with capsular rupture in 52% cases. Tumor was grade II in 71.8 % of cases. The expression of hormonal receptors was founded in 100% of cases. Two patients had an overexpression of HER2 (6.2%). There was no case of triple negative MBC. The OS at 5 and 10 years was 67.8% and 30.8% respectively. Prognostic factors were T4 (p = 0.015), involved nodes (p = 0.035), M+ (p = 0.01), SBR III (p = 0.0001) and HER2+++ (p = 0.001)., Conclusion: Contrary to breast cancer in women, our study showed that Tunisian MBC have positive hormone receptors in all cases. Although the overexpression of HER2 was low (8.33%) and there was no case of triple negative MBC, the prognosis was poor because of T4 stage, involved nodes, SBR III and distant metastases.

Nasopharyngeal carcinoma diagnosis is often made at a locally advanced stage (75 to 90% of cases) due to its deep localization. Concomitant radio-chemotherapy is the cornerstone of the treatment of locally advanced forms. The advent of intensity-modulated radiotherapy has improved oncological outcomes and reduced toxicity and is currently the gold standard for irradiation technique. For the locally advanced stage, the addition of induction chemotherapy has become the new standard care according to the latest international recommendations to reduce tumor volumes and act early on micro-metastases. Despite these therapeutic advances, the local and especially distant failure rate remains high. This article reviews current treatment strategies and discuss new approaches and perspectives of locoregional and systemic treatment to reduce treatment failures., (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The pre- and post-induction chemotherapy tumor volumes of nasopharyngeal carcinomas may be prognostic indicators for adapting the therapeutic strategy. The objective of our study is to assess the prognostic impact of pre- and post-induction chemotherapy volumes in patients treated for locally advanced nasopharyngeal carcinomas., Patients and Methods: This is a retrospective study including 52 patients with locally advanced nasopharyngeal carcinoma treated with 3 courses of induction chemotherapy (TPF) followed by intensity modulated radiotherapy associated with concomitant chemotherapy., Results: The median initial and post induction chemotherapy total volumes were 92.3 and 41.5mL, respectively. At 3 years, the LRFS, DMFS, DFS and OS were respectively 85.9%, 63.5%, 56.8% and 67.8%. In multivariate study, the combination of a high initial volume (>100mL) and post-chemotherapy volume (>35mL) was an independent factor for LRFS, DMFS, DFS and OS. The total baseline volume had a better predictive prognostic value for DFS and OS than the TNM classification (8th edition 2017)., Conclusion: The prognostic weight of tumor and nodal volumes was greater than the TNM classification (8th edition). The pre- and post-chemotherapy tumor volumes allow selecting a high-risk patients' subgroup "high initial and post chemotherapy volumes" in which it would be advisable to offer more intensive treatment regimens., (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Several new cancer therapies targeting signaling pathways involved in the growth and progression of cancer cells were developed as personalized medicine. Our study aimed to identify epidermal growth factor receptor (EGFR) mutations for TKI treatment in non-small-cell lung cancer (NSCLC) Tunisian patients. Methods: Analysis of the TKI sensitivity mutations in exons 18 to 21 of the EGFR gene and exon 15 of the B-raf gene was performed in 79 formalin fixed-paraffin embedded (FFPE) NSCLC samples using pyrosequencing. Results: EGFR mutations were detected in 34 cases among 79 (43%), with the predominance of the L861Q in exon 21 found in 35.3% of the cases (12 out of 34). Deletions in exon 19 were found in 8 cases (23.5%), and only one young male patient had the T790M mutation. Three patients harbored composite EGFR mutations (p.E746_A750del/p.L861R, p.E746_S752>V/p.S768I, and p.G719A/p.L861Q). Furthermore, the EGFR mutated status was significantly more frequent in female patients (p = 0.019), in non-smoker patients (p = 0.008), and in patients with metastasis (p = 0.044). Moreover, the B-raf V600E was identified in 5 EGFR negative patients among 39 analyzed samples (13.15%). Conclusion: The p.L861Q localized in exon 21 of the EGFR gene was the most common mutation identified in our patients (35.3%), whereas the “classic” EGFR mutations such as Del19 and p.L858R were found in 23.5% and 11.7% of the cases, respectively. Interestingly, most of p.L861X mutation-carrying patients showed good response to TKI treatment. Altogether, our findings suggest a particular distribution of the EGFR-TKIs sensitivity mutations in Tunisian NSCLC patients.

Objectives: Retroperitoneal sarcomas (RPSs) are rare mesenchymal tumors. The objective of this study was to discuss the different clinical, therapeutic and prognostic aspects of RPS in our institution., Methods: This was a retrospective study conducted at the Department of Medical Oncology in the Habib Bourguiba University Hospital in Sfax, including 19 patients who were treated for RPSs between 1999 and 2016., Results: The median age was 49 years (range: 18-83 years); 68.4% of the patients were female. The commonest symptom was abdominal pain (88%) and the median tumor size was 15 cm (range: 4-30 cm). Complete resection was achieved in only five cases (26.3%). The most common histological subtypes were liposarcoma (47.4%) and leiomyosarcoma (26.3%). Eight patients had a high-grade tumor (G2 = 2 or G3 = 6). Adjuvant radiotherapy was administered in 5 patients (26%). Seventeen patients were treated with chemotherapy; six received chemotherapy in an adjuvant treatment, three as a neoadjuvant treatment, and eight were treated during the palliative phase. Relapse was observed in 58% of cases. For all patients, the overall survival (OS) was 89.5% at 1 year and 40.3% at 5 years. Prognostic factors influencing OS were sex ( p  = 0.037), resection margins ( p  = 0.02), recurrence ( p  = 0.042), and radiotherapy ( p  = 0.023). In multivariate analysis, radiotherapy ( p  = 0.031) and histological subtype ( p  = 0.028) were independent factors influencing OS and disease-free survival (DFS) respectively., Conclusion: We showed that the treatment of RPSs relies on surgery with complete resection. Other factors, such as radiotherapy and the occurrence of relapse, also have an impact on OS. To facilitate surgery and to obtain negative resection margins, preoperative radiotherapy is indicated in selected patients with a high risk of relapse. Further prospective trials are warranted to select optimal therapies with less toxicity and better efficacy in reducing recurrences, mainly at a local level., (© 2022 [The Author/The Authors].)

(1) Background: Germline variants in BRCA1/BRCA2 genes explain about 20% of hereditary breast/ovarian cancer (HBOC) cases. In the present paper, we aim to identify genetic determinants in BRCA -negative families from the South of Tunisia. (2) Methods: Exome Sequencing (ES) was performed on the lymphocyte DNA of patients negative for BRCA mutations from each Tunisian family with a high risk of HBOC. (3) Results: We focus on the canonical genes associated with HBOC and identified missense variants in DNA damage response genes, such as ATM , RAD52 , and RAD54 ; however, no variants in PALB2 , Chek2 , and TP53 genes were found. To identify novel candidate genes, we selected variants harboring a loss of function and identified 17 stop-gain and 11 frameshift variants in genes not commonly known to be predisposed to HBOC. Then, we focus on rare and high-impact genes shared by at least 3 unrelated patients from each family and selected 16 gene variants. Through combined data analysis from MCODE with gene ontology and KEGG pathways, a short list of eight candidate genes ( ATM , EP300 , LAMA1 , LAMC2 , TNNI3 , MYLK , COL11A2 , and LAMB3 ) was created. The impact of the 24 selected genes on survival was analyzed using the TCGA data resulting in a selection of five candidate genes ( EP300 , KMT2C , RHPN2 , HSPG2 , and CCR3) that showed a significant association with survival. (4) Conclusions: We identify novel candidate genes predisposed to HBOC that need to be validated in larger cohorts and investigated by analyzing the co-segregation of selected variants in affected families and the locus-specific loss of heterozygosity to highlight their relevance for HBOC risk.

Background: This study aimed to explore the treatment modalities of relapsed osteosarcoma, treatment results, and prognostic factors., Methods: We conducted a retrospective study of patients treated for relapsed osteosarcoma between 2005 and 2019. Patient survival was compared according to age, performance status, time to relapse, and surgical treatment at the relapse. Values of p<0.05 were considered to indicate statistical significance., Results: We included 49 patients who were treated for osteosarcoma. During the 13-year study period, 16 patients had relapsed osteosarcoma (32.7%). Prognostic factors of relapse were age over 18 years (p = 0.03), axial tumors (p = 0.01), and positive surgical margins (p = 0.018). Nine patients had palliative chemotherapy at the time of relapse. After a median follow-up of 8 months (range: 4-65 months), the overall survival at 1 year, 2 years, and 5 years after diagnosis of the relapse was 46.7%, 31.1%, and 20.7%, respectively. Relapsed osteosarcoma patients who had good performance status, late relapse (after 12 months), as well as surgery of the relapsed disease had better overall survival (OS)., Conclusion: Surgical treatment of relapsed osteosarcoma should be performed whenever possible since it improves significantly the survival of patients. Good performance status and late relapse were also associated with better survival., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background and Aim: Despite the development and standardization of surgical techniques in the treatment of localized gastric adenocarcinoma, the loco-regional and metastatic recurrence rate remains high. A combined radiochemotherapeutic regimen (the MacDonald regimen) as well as perioperative chemotherapy allows a significant improvement in the survival of patients with localized gastric adenocarcinoma with a reduction in the recurrence rate compared to surgery alone. The purpose of this review is to specify the best therapeutic approach in the treatment of localized gastric cancer., Methods: We performed a systemic search of Medline, Embase, and the Cochrane Central Register of Controlled Trials using PubMed, Google Scholar, and Ovid without language restriction. Hazard ratio (HR) with 95% confidence interval (CI) was reported., Results: We pooled 727 patients from two phase III randomized controlled trials. There was a benefit of perioperative chemotherapy versus surgery alone on the overall survival (OS) (HR = 0.72, 95% CI: 0.55-0.95) and on disease free survival (DFS) (HR = 0.65, CI: 0.50-0.85). Adjuvant chemotherapy was superior to surgery alone based on OS and disease free survival (CLASSIC study HR = 0.72, CI: 0.52-1 and HR = 0.56, CI: 0.44-0.72, respectively). Adjuvant radiochemotherapy was superior to surgery alone (HR = 1.35, 95% CI: 1.09-1.66; P  = 0.005)., Conclusion: A face-to-face comparison of perioperative chemotherapy versus adjuvant chemotherapy versus chemoradiotherapy is necessary., (© 2022 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Nasopharyngeal carcinoma has the highest metastatic potential of all head and neck cancers. The survival time of patients with nasopharyngeal carcinoma has improved significantly in the last decades due to the use of combination of chemotherapy and radiotherapy, as well as advances in radiotherapy techniques. However, appropriately 30% of patients with nasopharyngeal carcinoma suffer a poor prognosis, mainly due to distant metastasis., Objective: The study aimed to identify the survival and prognostic factors in metastatic nasopharyngeal carcinoma., Methods: A retrospective analysis was conducted in patients treated for synchronous metastatic nasopharyngeal carcinoma or metachronous metastatic nasopharyngeal carcinoma for 14 years (2003-2016). Overall survival was analyzed using the Kaplan-Meier method and compared using the log-rank test for the whole population and both groups of patients. Multivariate analysis was performed using the Cox model; p-values < 0.05 were considered to indicate statistical significance., Results: One hundred and twelve patients with metastatic nasopharyngeal carcinoma were included (51 patients with metastatic nasopharyngeal carcinoma, and 61 patients with metachronous metastatic nasopharyngeal carcinoma). In the whole population, the median overall survival was 10 months (1-156 months). In the multivariate analysis, female gender, poor performance status (WHO > 1) and metachronous metastasis were independent prognostic factors. In the metastatic nasopharyngeal carcinoma patients, the median overall survival was 13 months (1-156 months). In multivariate analysis, independent prognostic factors were non-oligometastatic disease, severe (G3‒G4) chemotherapy toxicity and the lack of nasopharyngeal and metastatic site irradiation. In the metachronous metastatic nasopharyngeal carcinoma patients, the median overall survival was 7 months (1-41 months). In multivariate analysis, the poor performance status (WHO > 1) was an independent metastatic nasopharyngeal carcinoma prognostic factor., Conclusion: Oligometastatic patients with synchronous metastatic nasopharyngeal carcinoma had better survival. The locoregional treatment of primitive nasopharyngeal carcinoma improved survival in patients with metastatic nasopharyngeal carcinoma who responded to induction chemotherapy. Local irradiation of metastatic sites improved survival of metastatic nasopharyngeal carcinoma patients. Grade 3 or 4 chemotherapy toxicity altered survival among patients with synchronous metastatic nasopharyngeal carcinoma., (Copyright © 2020 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Previous studies have shown that poor prognostic indicators of inflammatory breast cancer (IBC) include younger age at diagnosis, poorer tumor grade, negative estrogen receptor, lesser degree of pathological response in the breast and lymph nodes., Methods: This is a retrospective study conducted over a period of 12 years between January 2008 and December 2019 at the medical oncology department at Habib Bourguiba University Hospital in Sfax. We included in this study women with confirmed IBC. We excluded patients with no histological evidence, those whose medical records were unusable. Data collection was done from patient files. The aim of this study was to analyze the factors of poor prognosis of this entity., Results: During a period of 12 years (2008-2019), 2879 cases of breast cancer were treated at Habib Bourguiba hospital in Sfax. 81 IBC were included. The incidence of IBC was 3%. The average age was 52.4 years (26-87 years). Invasive ductal carcinoma was the most frequent histological type (85.7%). Hormone receptor were positive in 64%. Human Epidermal Growth Factor Receptor-2 (HER2) was overexpressed in 35.9% of cases. The proliferation index Ki-67 was analyzed in 34 cases. It was >20% in 24 cases. Luminal A, luminal B, HER2+++, triple negative were found in 13%, 50.7%, 16% and 20% respectively. Metastases at diagnosis were found in 38%. Poor prognostic factors significantly influencing overall survival in univariate analysis were metastatic stage, high SBR grade, lymph node involvement, in particular greater than 3 nodes, negative hormone receptors, triple-negative molecular profile and occurrence of relapse., Conclusion: Number of positive lymph nodes greater than 3 and the occurrence of relapse were independent prognostic factors in case of localized IBC. Metastatic stage was associated with a very poor prognosis.

Background: Cardiotoxicity following breast cancer radiotherapy (RT) represents one of the most redoubtable toxicities. The Global longitudinal strain measurement (GLS) based on 2D speckle tracking imaging (STI) allows detection of left ventricular (LV) dysfunction at a subclinical stage. The aim of this prospective study was to detect patients at risk of cardiotoxicity using echocardiographic parameters and to determine the association between segmental RT doses and early cardiac toxicity., Material and Methods: The STI was performed prior to RT and at 3, 6 and 12 months after. The association between subclinical LV dysfunction, defined as a reduction of GLS more than 10% from the initial value, radiation doses to different LV segments and non-radiation factors were performed based on multivariate analyses., Results: From June 2017 to August 2018, a total of 103 female patients were included. Sixty patients had left sided RT. Seven patients (7.8%) developed a GSL impairment. The segmental alterations predominated in the anteroseptal and apical LV segments. The mean Dmean in altered segments was significantly higher than in non-altered segments (6.7 ± 8.8Gy-7.8 ± 8.9Gy vs 4.9 ± 7.9-5.4 ± 8.2Gy; p < 0.05). Age > 55 years and obesity were important confounding factors that should be considered during radiotherapy planning., Conclusion: The results of our study show that radiation dose is correlated with the subclinical LV segments' alteration. Global heart delineation seems to be insufficient during the breast radiotherapy planning. Segmental delineation of the LV may be an interesting alternative to limit segmental doses and to reduce the risk of subclinical alterations. A mean dose of 5Gy could be proposed in exposed heart segment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Fractionating whole blood and separating its constituent components one from another is an essential step in many clinical applications. Currently blood sample handling and fractionation processes remain a predominantly manual task that require well-trained operators to produce reliable and reproducible results. Herein, we demonstrate an advanced on-chip whole human blood fractionation and cell isolation process combining (i) an aqueous two-phase system (ATPS) to create complex separation layers with (ii) a centrifugal microfluidic platform (PowerBlade) with active pneumatic pumping to control and automate the assay. We use a polyethylene glycol (PEG) and dextran (DEX) mixture as the two-phase density gradient media and our automated centrifugal microfluidic platform to fractionate blood samples. Different densities of precisely tuned PEG-DEX solutions were tested to match each of the cell types typically targeted during blood fractionation applications. By employing specially designed microfluidic devices, we demonstrate the automation of the following steps: loading of a whole blood sample on-chip, layering of the blood on the ATPS solution, blood fractionation, precise radial repositioning of the fractionated layers, and finally extraction of multiple, selected fractionated components. Fractionation of up to six distinct layers is shown: platelet-rich plasma, buffy coat, PEG, DEX with neutrophils, red blood cells (RBCs) and high density gradient media (HDGM). Furthermore, through controlled dispensing of HDGM to the fractionation chamber, we show that each of the fractionated layers can be repositioned radially, on-the-fly, without disturbing the interfaces, allowing precise transfer of target fractions and cell types into external vials via a chip-to-world interface. Cell counting analysis and cell viability studies showed equivalence to traditional, manual methods. An overall cell viability greater than 90% of extracted cells demonstrates that the proposed approach is suitable for cell isolation applications. This proof-of-principle demonstration highlights the utility of the proposed system for automated whole blood fractionation and isolation for blood cell applications. We anticipate that the proposed approach will be a useful tool for many clinical applications such as standard cell isolation procedures and other bioanalytical assays ( e.g. , circulating tumor cells, and cell and gene therapy).

Schiff bases encompassing a 1,2,3-triazole motif were synthesized using an efficient multi-step synthesis. The formations of targeted Schiff base ligands were confirmed by different spectroscopic techniques (FT-IR, 1 H NMR, 13 C NMR, and CHN analysis). The spectral data analysis revealed that the newly designed hydrazones exist as a mixture of trans-E and cis - E diastereomers. Densityfunctional theory calculations (DFT) for the Schiff bases showed that the trans-trans form has the lowest energy structure with maximum stability compared to the other possible geometrical isomers that could be present due to the orientation of the amidic NH-C=O group. The energy differences between the trans - trans on one side and syn-syn and syn-trans isomers on the other side were 9.26 and 5.56 kcal/mol, respectively. A quantitative structure-activity relationship investigation was also performed in terms of density functional theory. The binding affinities of the newly synthesized bases are, maybe, attributed to the presence of hydrogen bonds together with many hydrophobic interactions between the ligands and the active amino acid residue of the receptor. The superposition of the inhibitor N3 and an example ligand into the binding pocket of 7BQY is also presented. Further interesting comparative docking analyses were performed. Quantitative structure-activity relationship calculations are presented, illustrating possible inhibitory activity. Further computer-aided cytotoxicity analysis by Drug2Way and PASS online software was carried out for Schiff base ligands against various cancer cell lines. Overall, the results of this study suggest that these Schiff base derivatives may be considered for further investigation as possible therapeutic agents for COVID-19.

Objectives: The study aimed to investigate the epidemiological and clinical characteristics as well as the therapeutic results in patients with locoregional (LR) relapse after treatment of nasopharyngeal carcinoma (NPC)., Methods: We retrospectively reviewed the medical records of patients with local and/or regional recurrent NPC over 13 years (2003-2015)., Results: Twenty-five patients were treated for local or/and local-regional recurrence of NPC. The rate of LR relapse was 7.2%. The mean age of the patients was 46 ± 13.9 years. The median time to relapse was 25 months. The recurrence was nasopharyngeal in 17 patients, nasopharyngeal and neck lymph nodes in 7 patients, and neck lymph nodes in 1 patient. Fifteen relapsed patients had a locally advanced disease (rT3-rT4). Patients who had initially T1 or T2 tumor had a locally advanced relapsed disease (rT3rT4) in 27.3% and patients whose disease was initially classified as T3 or T4 had a locally advanced relapsed disease (rT3T4) in 85.7% ( P = .005, Fisher test). Twelve patients had chemotherapy after relapse. Chemotherapy was followed by concurrent chemoradiotherapy in 3 patients and by radiotherapy (RT) in 4 patients. Nine patients had concurrent chemoradiotherapy and 1 patient had exclusive RT. The overall survival (OS) at 1 year, 3 years, and 5 years was, respectively, 58%, 18%, and 10%. The OS was significantly higher in patients with good performance status at the time of relapse (World Health Organization = 1; P = .01) and in patients with late relapse (after 2 years; P = .03)., Conclusions: Locoregional relapse rate in our study was 7.2%. Locoregional reirradiation was the mainstay treatment modality in relapsed NPC. Relapsed NPC had a poor prognosis with a 5-year survival rate of 18%. The OS was significantly higher in patients with good performance status and in patients with late relapse (after 2 years).

Aim: The objective of this study is to report the therapeutic results of the preservation strategy in locally advanced laryngeal cancers., Patients and Methods: Between January 2008 and December 2015, 24 patients with locoregional advanced non-metastatic laryngeal cancer (T2-4/N0-2) were collected retrospectively. Different therapeutic sequences were used: either induction chemotherapy followed by concurrent chemoradiotherapy or induction chemotherapy followed by radiotherapy or concurrent chemoradiotherapy or radiotherapy alone., Results: The objective response rate was 85.7%. Overall survival rates at 1 year, 3 years and 5 years were 91.3%, 80.2% and 53.5%, respectively. Administration of induction chemotherapy did not improve overall survival. The 1-year overall survival was 83.3% in the induction chemotherapy group vs 94.1% for those who did not received induction chemotherapy (p = 0.7)., Conclusion: Our study showed the feasibility of this preservation strategy in clinical practice, with acceptable term toxicity.

The HER2 receptor (Human Epidermal Growth Receptor 2) is a transmembrane receptor with tyrosine kinase activity that is over-expressed in 25-30 % of breast carcinomas. Its activation is associated with an exaggeration of cell proliferation with an increase in repair capacity resulting in increased radioresistance. On cardiac tissues, HER2 receptor activation plays a cardio-protective role. Trastuzumab, the first anti-HER2 drug used to treat patients with breast cancer overexpressing HER2 receptor , inhibits the cascade of reactions resulting in the proliferation of tumor cells, thus restoring cellular radiosensitivity. However, the combination of Trastuzumab with radiation therapy also removes HER2 receptor cardio-protective role on myocardial cells which increases the risk of cardiotoxicity. Thus, the concomitant association of these two modalities has long been a subject of controversy. Recent advances in radiation therapy technology and early detection of cardiac injury may limit the cardiotoxicity of this combination. Through this review, we developed the biological basis and the benefit-risk of concomitant combination of radiotherapy and Trastuzumab in adjuvant treatment of breast cancers overexpressing HER2 and we discuss the modalities of its optimization., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The highly contagious nature of Covid-19 attracted us to this challenging area of research, mainly because the disease is spreading very fast and until now, no effective method of a safe treatment or a vaccine is developed. A library of novel 1,2,3-triazoles based 1,2,4-triazole, 1,3,4-oxadiazole and/or 1,3,4-thiadiazole scaffolds were designed and successfully synthesized. Different spectroscopic tools efficiently characterized all the newly synthesized hybrid molecules. An interesting finding is that some of the newly designed compounds revealed two isomeric forms. The ratio is affected by the size of the attached group as well as the type of the heteroatom forming the side ring attached to the central 1,2,3-triazole ring. The experimental spectroscopic data is in agreement with the DFT calculations at B3LYP 6-31G (d,p) with regard to the geometrical conformation of the prepared compounds. The DFT results revealed that the stability of one isomeric form over the other in the range of 0.057-0.161 Kcal mol -1 . A docking study was performed using PyRx and AutoDockVina to investigate the activity of the prepared 1,2,3-triazoles as antiviral agents. Bond affinity scores of the 1,2,3-triazole derivatives were detected in the range of -6.0 to -8.8 kcal/mol showing binding to the active sites of the 6LU7 protease and hence could be anticipated to inhibit the activity of the enzyme. Verification of the docking results was performed using the M pro alignment of coronaviruses substrate-binding pockets of COVID-19 against the ligands. As per these results, it can be proposed that the title hybrid molecules are acceptable candidates against COVID-19 for possible medicinal agents., Competing Interests: The authors declare no conflict of interest., (© 2021 Wiley‐VCH GmbH.)

Purpose: To describe the clinical, therapeutic and prognostic features of ductal carcinomas of the parotid gland., Material and Methods: Five patients with ductal carcinoma of the parotid gland (primary and secondary carcinoma) treated, between 2007 and 2019, in our ENT department, were reviewed., Results: Four men and one woman were included. The mean age was 61,4 years. One patient had a history of an invasive ductal carcinoma of the breast. Four patients consulted for swelling in the parotid region. One patient referred to our department for dysfunction of facial nerve. Skin invasion was found in one case. Four patients underwent total parotidectomy with sacrifice of the facial nerve (three cases). One patient underwent extended parotidectomy involving the skin. An ipsilateral selective neck dissection was performed in four cases. One patient had a parotid gland biopsy. Ductal carcinoma was primary in four cases and metastatic from breast origin in one case. Four patients were treated with postoperative radiotherapy. Remission was obtained in three cases. One patient had a local and meningeal recurrence. The patient with metastatic carcinoma had pulmonary, bone, hepatic and brain progression., Conclusion: Ductal carcinoma is a rare and aggressive tumor of the parotid gland. It can be primary or secondary. The treatment is based on surgery and radiotherapy. The prognosis is poor., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: The incidence of breast cancer (BC) and/or ovarian cancer (OC) is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum of BRCA mutations remains little explored in Tunisian patients in particular in the southern region., Methods: We sequenced the entire coding regions of BRCA1and BRCA2 genes using next generation sequencing (NGS) in 134 selected patients with BC and/or OC., Results: Among the 134 patients, 19 (14.17%) carried pathogenic mutations (10 are BRCA1 mutation carriers and 9 are BRCA2 mutation carriers) that are mainly frameshift index (76.9%). Interestingly, 5 out of the 13 variants (38.46%) were found at least twice in unrelated patients, as the c.1310-1313 delAAGA in BRCA2 and the c.5030&#95;5033 delCTAA that has been identified in 4/98 BC patients and in 3/15 OC patients from unrelated families with strong history of cancer. Besides recurrent mutations, 6 variant (4 in BRCA1 and 2 in BRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A > T, (K3326*) in BRCA2 exon 27. BRCA carriers correlated significantly with tumor site (p = 0.029) and TNBC cases (p = 0.008). In the groups of patients aged between 31 and 40, and 41-50 years, BRCA1 mutations occurred more frequently in patients with OC than those with BC, and conversely BRCA2 carriers are mostly affected with BC (p = 0.001, and p = 0.044 respectively)., Conclusions: The overall frequency of the BRCA germline mutations was 14.17% in patients with high risk of breast/ovarian cancer. We identified recurrent mutations as the c.1310&#95;1313 delAAGA in BRCA2 gene and the c.5030&#95;5033 delCTAA in BRCA1 gene that were found in 4% and 20% of familial BC and OC respectively. Our data will contribute in the implementation of genetic counseling and testing for families with high-risk of BC and/or OC.

The development of technology for the rapid, automated identification of bacterial culture isolates can help regulatory agencies to shorten response times in food safety surveillance, compliance, and enforcement as well as outbreak investigations. While molecular methods such as polymerase chain reaction (PCR) enable the identification of microbial organisms with high sensitivity and specificity, they generally rely on sophisticated instrumentation and elaborate workflows for sample preparation with an undesirably high level of hands-on engagement. Herein, we describe the design, operation and performance of a lab-on-a-chip system integrating thermal lysis, PCR amplification and microarray hybridization on the same cartridge. The assay is performed on a centrifugal microfluidic platform that allows for pneumatic actuation of liquids during rotation, making it possible to perform all fluidic operations in a fully-automated fashion without the need for integrating active control elements on the microfluidic cartridge. The cartridge, which is fabricated from hard and soft thermoplastic polymers, is compatible with high-volume manufacturing (e.g., injection molding). Chip design and thermal interface were both optimized to ensure efficient heat transfer and allow for fast thermal cycling during the PCR process. The integrated workflow comprises 14 steps and takes less than 2 h to complete. The only manual steps are related to loading of the sample and reagents on the cartridge as well as fluorescence imaging of the microarray. On-chip lysis and PCR amplification both provided results comparable to those obtained by bench-top instrumentation. The microarray, incorporating a panel of oligonucleotide probes for multiplexed detection of seven enterohemorrhagic E. coli priority serotypes, was implemented on a cyclic olefin copolymer substrate using a novel activation scheme that involves the conversion of hydroxyl groups (derived from oxygen plasma treatment) into reactive cyanate ester using cyanogen bromide. On-chip hybridization was demonstrated in a non-quantitative fashion using fluorescently-labelled gene markers for E. coli O157:H7 (rfbO157, eae, vt1, and vt2) obtained through a multiplexed PCR amplification step.

Male Breast Cancer (MBC) is a rare and aggressive disease that is associated with genetic factors. Mutations in BRCA1 and BRCA2 account for 10% of all MBC cases suggesting that other genetic factors are involved. The aim of the present study is to screen whole BRCA1 and BRCA2 exons using the Ampliseq BRCA panel in Tunisian MBC patients with family history. Furthermore, we performed exome sequencing using the TruSight One sequencing panel on an early onset BRCA negative patient. We showed that among the 6 MBC patients, only one (MBC-F1) harbored a novel frameshift mutation in exon 2 of the BRCA2 gene (c.17-20delAAGA, p.Lys6Xfs) resulting in a short BRCA2 protein of only 6 amino-acids. We selected 9 rare variants after applying several filter steps on the exome sequencing data. Among these variants, and based on their role in breast carcinogenesis, we retained 6 candidate genes (MSH5, DCC, ERBB3, NOTCH3, DIAPH1, and DNAH11). Further studies are needed to confirm the association of the selected genes with family MBC.

We present here a new method for controlling the droplet size in step emulsification processes on a centrifugal microfluidic platform, which, in addition to the centrifugal force, uses pneumatic actuation for fluid displacement. We highlight the importance of the interplay between buoyancy effects and the flow rate at the step junction, and provide a simple analytical model relating these two quantities to the size of the droplets. Numerical models as well as experiments with water-in-oil emulsions are performed in support of the proposed model.

Background: Trastuzumab improves therapeutic outcomes among patients with human epidermal growth factor receptor 2-positive breast cancer (BC). However, it is associated with a risk of treatment-induced cardiotoxicity. The aims of this study were to determine the frequency of trastuzumab-induced cardiotoxicity (TIC) in Tunisian patients, to study the effects of trastuzumab on cardiac biomarkers and echocardiographic parameters using the speckle tracking technique and to identify risk factors of occurrence of TIC., Patients and Methods: Fifty women with newly diagnosed human epidermal growth factor receptor 2-positive BC treated with or without anthracycline followed by taxane and trastuzumab were enrolled, from November 2016 to December 2018, to be evaluated every 3 months during trastuzumab treatment (total of 15 mo) using echocardiograms and blood samples. Left ventricular ejection fraction (LVEF) and peak systolic left ventricular longitudinal myocardial strain were calculated. Ultrasensitive troponin I (TNI) and N-terminal pro-B-type natriuretic peptide (NT pro-BNP) were also measured., Results: LVEF decreased from 62±3.12% to 59±3.3% (P=0.005) over 15 months. Seven patients (14%) developed cardiotoxicity, as defined by the European Society of Cardiology; of these patients, 2 (4%) had symptoms of heart failure. Hypertension, left ventricular longitudinal myocardial strain, Log TNI, and NT pro-BNP measured at the completion of anthracyclines were significantly correlated to TIC occurrence. At multivariate analysis, the degree of LVEF decline was the only independent factor correlated to TIC (hazard ratio=2.4; 95% confidence interval=1.2-6.03; P=0.049). This TIC was reversible in 86% of cases., Conclusion: In patients with BC treated with trastuzumab, in addition to the evaluation of the LVEF, systolic longitudinal strain, TNI, and NT pro-BNP measured at the completion of anthracyclines are useful in the prediction of subsequent TIC.

A multiplexed droplet PCR (mdPCR) workflow and detailed protocol for determining epigenetic-based white blood cell (WBC) differential count is described, along with a thermoplastic elastomer (TPE) microfluidic droplet generation device. Epigenetic markers are used for WBC subtyping which is of important prognostic value in different diseases. This is achieved through the quantification of DNA methylation patterns of specific CG-rich regions in the genome (CpG loci). In this paper, bisulfite-treated DNA from peripheral blood mononuclear cells (PBMCs) is encapsulated in droplets with mdPCR reagents including primers and hydrolysis fluorescent probes specific for CpG loci that correlate with WBC sub-populations. The multiplex approach allows for the interrogation of many CpG loci without the need for separate mdPCR reactions, enabling more accurate parametric determination of WBC sub-populations using epigenetic analysis of methylation sites. This precise quantification can be extended to different applications and highlights the benefits for clinical diagnosis and subsequent prognosis.

The forkhead box (FOXA) family of transcription factors regulates gene expression and chromatin structure during tumorigenesis and embryonic development. Until now, the relationship between FOXA1 and the nasopharyngeal carcinoma (NPC) has not yet been reported. Therefore, our purpose is to analyze the expression of FOXA1 in 56 NPC patients compared to 10 normal nasopharyngeal mucosae and to correlate the expression with the clinicopathological features. Besides, we investigated the association between FOXA1 and LMP1 gene expression, as well as the EMT markers namely the E-cadherin and Twist1. Among 56 NPC tissues, 34 (60.7%) cases were positive for FOXA1. Furthermore, we noticed that FOXA1 expression correlated with TNM ( p = 0.037), and age at diagnosis ( p = 0.05). Moreover, positive expression of FOXA1 is likely to be associated with prolonged disease-free survival and overall survival rates. On the other hand, we observed a positive association between the expression of E-cadherin and FOXA1 ( p = 0.0051) whereas Twist1 correlated negatively with FOXA1 ( p = 0.004). Furthermore, knowing that LMP1 plays a key role in the pathogenesis of NPC, we explored the association of FOXA1 with the LMP1 gene expression in both NPC cell lines and tissues. We found that, in the C666-1 which displays low levels of LMP1, the expression of FOXA1 is high, and inversely in the C15 cell line that expresses a high level of LMP1, the level of FOXA1 is low. Besides, in accordance to our results, we found that in NPC tissues there is a negative association between LMP1 and FOXA1. In conclusion, our results suggest that the overexpression of FOXA1 is associated with a nonaggressive behavior and favorable prognosis in NPC patients. FOXA1 could contribute in the EMT process through key factors as E-cadherin, Twist1, and LMP1., Competing Interests: The authors report no conflicts of interests in this work., (Copyright © 2020 Nihel Ammous-Boukhris et al.)

We describe the use of periodic micropillar arrays, produced from cyclic olefin copolymer using high-fidelity microfabrication, as templates for colorimetric DNA detection. The assay involves PCR-amplified gene markers for E. coli O157:H7 ( rfbO157 , eae , vt1 , and vt2 ) incorporating a detectable digoxigenin label, which is revealed through an immunoenzymatic process following hybridization with target-specific oligonucleotide capture probes. The capacity of micropillar arrays to induce wicking is used to distribute and confine capture probes with spatial control, making it possible to achieve a uniform signal while allowing multiple, independent probes to be arranged in close proximity on the same substrate. The kinetic profile of color pigment formation on the surface was followed using absorbance measurements, showing maximum signal increase between 20 and 60 min of reaction time. The relationship between microstructure and colorimetric signal was investigated through variation of geometric parameters, such as pitch (10-50 μm), pillar diameter (5-40 μm), and height (16-48 μm). Our findings suggest that signal intensity is largely influenced by the edges of the pillars and less by their height such that it deviates from a linear relationship when both aspect ratio and pillar density become very high. A theoretical model used to simulate the changes in surface composition at the molecular level suggests that differences in the temporal and spatial accumulation of assay components account for this observation.

Modern high-precision radiotherapy techniques have recently incorporated the notion of anatomical variations of the patient during treatment and have tried to adapt the treatment planning to them. Adaptive radiotherapy for nasopharyngeal tumors is starting to prove its benefit nowadays. His interest is constantly being evaluated. The variations encountered during the treatment are both geometric and dosimetric. They are represented by a reduction in the macroscopic tumors volume, a change in its position and a consequent dosimetric impact. The changes also concern organs at risk with a reduction of glandular structure volumes, and a different position which increases their doses. Delivered doses to noble structures (brainstem and spinal cord) may also increase. However, difficulties are encountered in its realization. There is a problem to perfectly reproduce the patient position during the second acquisition, which impacts the fusion quality between the two CT scans. This generates an imprecision in the definition of the same treatment isocentre on the second scanner. Also, there is a difficulty in accumulated doses calculation. The indication of adaptive radiotherapy remains a subject of controversy. It should be proposed for a subgroup of patients who could benefit from this new strategy. We present here an update on the state of the art of adaptive radiotherapy for nasopharyngeal cancer., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The aim of this work is to evaluate the anatomical changes of the glandular structures during the NPC IMRT and to study their dosimetric impacts., Patients and Methods: Twenty patients receiving IMRT for NPC were included. For each patient, a second dosimetric CT was performed at a dose of 38Gy, which was fused with the initial planning dosimetric CT. We calculated the volume percent change, the positional and dosimetric variation between the 2 scanners for the glandular structures (parotid, submaxillary, thyroid and pituitary)., Results: We observed a decrease in the volume of right and left parotids (-27.9% and -27.54%). It was correlated with the initial dose planned at its level. For the sub maxillary glands, the decrease was -36.1% on the right and -27.28% on the left. The value of reduction of the thyroid gland was -18.01%. A medial supra-millimeter migration of 2 and 1.15mm was found for right and left parotid glands respectively, correlated with GTV N reduction volume. We found a significant increase in mean doses for the parotid glands. It was 1.8±2.3Gy for the right and 1.5±2.7Gy for the left. For the right sub maxillary gland, the increase was about 0.35±2Gy and 3.79±5.2Gy for the thyroid., Conclusion: The modifications observed for glandular structures during NPC IMRT can explain the different toxicities caused by radiation. It seems also that a careful adaptation of the treatment plan should be considered during therapy., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background and Purpose: To assess anatomic changes during intensity modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) and to determine its dosimetric impact., Patients and Methods: Twenty patients treated with IMRT for NPC were enrolled in this study. A second CT was performed at 38 Gy. Manual contouring of the macroscopic tumor volumes (GTV) and the planning target volumes (PTV) were done on the second CT. We recorded the volumes of the different structures, D98 %, the conformity, and the homogeneity indexes for each PTV. Volume percent changes were calculated., Results: We observed a significant reduction in tumor volumes (58.56 % for the GTV N and 29.52 % for the GTV T). It was accompanied by a significant decrease in the D98 % for the 3 PTV (1.4 Gy for PTV H, p = 0.007; 0.3 Gy for PTV I, p = 0.03 and 1.15 Gy for PTV L, p = 0 0.0066). In addition, we observed a significant reduction in the conformity index in the order of 0.02 (p = 0.001) and 0.01 (p = 0.007) for PTV H and PTV I, respectively. The conformity variation was not significant for PTV L. Moreover, results showed a significant increase of the homogeneity index for PTV H (+ 0.03, p = 0.04) and PTV L (+ 0.04, p = 0.01)., Conclusion: Tumor volume reduction during the IMRT of NPC was accompanied by deterioration of the dosimetric coverage for the different target volumes. It is essential that a careful adaptation of the treatment plan be considered during therapy for selected patients., (© 2019 Greater Poland Cancer Centre. Published by Elsevier B.V. All rights reserved.)

Background: To evaluate the patterns of failure in patients treated for head and neck carcinoma of unknown primary and to discuss treatment practices concerning radiotherapy target volumes definition and dose prescription., Methods: Eleven patients presenting a locoregional recurrence after head and neck carcinoma of unknown primary treatment with curative-intent radiochemotherapy performed between 2007 and 2017 in the departments of radiation oncology of 2 French cancer institutes. Images of the computed tomography scan or the magnetic resonance imaging performed at the time of the recurrence were fused with those of the simulation computed tomography scan to delimit a volume corresponding to the recurrence and to define the area of relapse compared to the volumes treated., Results: Irradiation was unilateral in 6 cases and bilateral in 5 cases. The median time to onset of recurrence was 7.24 months (extreme 3-67.7 months). Six patients had only a neck node recurrence, 3 had a neck node and subsequent primary recurrence, and 1 had only a median subsequent primary recurrence. Only 1 patient had synchronous distance progression to local recurrence. All neck node recurrences were solitary and ipsilateral. The subsequent primary recurrences were in the oropharynx in 3 cases and in the contralateral oral cavity in one case. All neck node recurrences were into the irradiated volume. The subsequent primary recurrences were either within or in border of the irradiated volumes. The median of the mean dose, received by neck node recurrences, was 69.9 Gy and that of the mean dose, minimum dose, maximum dose, and dose received by 95% of the volume of recurrence was 66.7 Gy. For the primary relapses, the median of the mean dose was 52.1 Gy and that of the mean dose, minimum dose, maximum dose, and dose received by 95% of the volume of recurrence was 39.9 Gy., Conclusions: All local nodal recurrences occurred at sites that received high radiotherapy doses and doses received by sites of eventual failure did not vary significantly from sites that remain in control.

Epigenetic markers attract increasing attention for the study of phenotypic variations, which has led to the investigation of cell-lineage DNA methylation patterns that correlate with human leukocyte populations for obtaining counts of white blood cell (WBC) subsets. Current methods of DNA methylation analysis involve genome sequencing or loci-specific quantitative PCR (qPCR). Herein, a multiplexed digital droplet PCR (ddPCR) workflow for determining epigenetic-based WBC differential count is described for the first time. A microfluidic emulsification device fabricated from a commercially available thermoplastic elastomer (e.g., Mediprene) promotes customizability and cost-effectiveness of the methodology, which are prerequisites for translation into clinical and point-of-care diagnostics. Bisulfite-treated DNA from peripheral blood mononuclear cells and whole blood is encapsulated in droplets with ddPCR reagents containing primers and fluorescent hydrolysis probes specific for CpG loci correlated with WBC sub-population types. The method enables multiplexed detection of various methylation sites within a single droplet. Both qPCR and immunofluorescence staining (IF) were conducted to validate the capacity of the ddPCR methodology to accurately determine WBC sub-populations using epigenetic analysis of methylation sites. ddPCR results correlated closely to cell proportions obtained using IF, whereas qPCR significantly underestimated these values for both high and low copy number gene targets.

In the paper, we propose a new deep learning-based method for segmenting nasopharyngeal carcinoma (NPC) in the nasopharynx from three orthogonal CT images. The proposed method introduces a cascade strategy composed of two-phase manners. In CT images, there are organs, called non-target organs, which NPC never invades. Therefore, the first phase is to detect and eliminate non-target organ regions from the CT images. In the second phase, NPC is extracted from the remained regions in the CT images. Convolutional neural networks (CNNs) are applied to detect non-target organs and NPCs. The proposed system determines the final NPC segmentation by integrating three results obtained from coronal, axial and sagittal images. Moreover, we construct two CNN-based NPC detection systems using one kind of overlapping patches with a fixed size and various overlapping patches with different sizes. From the experiments using CT images of 70 NPC patients, our proposed systems, especially the system using various patches, achieves the best performance for detecting NPC compared with conventional NPC detection methods., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aims: CD155 is a ligand of the NK activating receptor DNAM-1, it has been described in a variety of human malignancies, but its expression in breast cancer remains unclear and poorly studied., Main Methods: CD155 expression and NK cells infiltration were investigated in 158 patients with breast cancer by immunohistochemistry (IHC). Statistical analyses were performed to evaluate correlations of CD155 expression with clinical-pathological features, prognosis and tumor immunity., Key Findings: Tumor cytoplasmic CD155 (cyt-CD155) was associated with lymphovascular invasion (p = 0.011), and membranous CD155 (m-CD155) was strongly correlated with the presence of Tumor Infiltrating natural killer cells (NK-TILs) (p = 0.0003). Survival analysis demonstrated that patients with high cyt-CD155 had a significantly worse overall survival (p < 0.001) and death free survival (p = 0.014) than those with low expression, while high levels of m-CD155 correlated with a better prognosis (p = 0.037). Furthermore, we found that patients with m-CD155 Low /NK Low tumors had a significantly reduced overall survival (p = 0.012). Multivariate analysis showed that positive tumor m-CD155 status was a significant independent marker of good prognosis. Meanwhile, high cyt-CD155 expression was identified as an independent poor prognostic predictor, suggesting a key role in this malignancy., Significance: Altogether, our results revealed that cyt-CD155 was associated with invasiveness and poorer prognosis, but the concomitant presence of m-CD155 and NK-TILs had an opposite prognostic relevance in breast cancer. These results raised the importance of CD155 IHC analysis to elucidate biomarker localization, leading to better understand and design therapeutic molecule targeting CD155 in breast tumors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This paper describes the development of an on-chip nucleic acid (NA) extraction assay from whole blood using a centrifugal microfluidic platform that allows for pneumatic actuation of liquids during rotation. The combination of pneumatic and centrifugal forces makes it possible to perform fluidic operations without the need for integrating active control elements on the microfluidic cartridge. The cartridge is fabricated from thermoplastic polymers (e.g., Zeonor 1060R) and features a simple design that is compatible with injection molding. In addition, the cartridge is interfaced with two external vials for off-chip storage of the blood sample and retrieval of the eluted NA solution, respectively. On-chip capture of NAs is performed using an embedded solid-phase extraction matrix composed of commercial glass microfiber filters (Whatman GF/D and GF/F). The yield of the automated, on-chip extraction protocol, determined by measuring absorbance at 260 nm, is comparable to some of the best manually operated kits (e.g., Qiagen QIAamp DNA Mini Kit) while providing low assay-to-assay variability due to the high level of control provided by the platform for each processing step. The A260/A280 and A260/A230 ratios of the absorbance spectra also reveal that protein contamination of the sample is negligible. The capability of the pneumatic platform to circulate air flux through the microfluidic conduit was used to dry leftover ethanol residues retained in the capture matrix during washing. This method, applied in combination with localized heating, proved effective for reducing ethanol contamination in eluted samples from ∼12% to 1% (v/v).

Although its incidence has declined over last half-century, gastric cancer remains the second most frequent cause of cancer death in the world. The ⅔ of the patients are metastatic at diagnosis. The current study aimed to identify some determinants of survival in patients with metastatic gastric carcinoma., Materials and Methods: It was a retrospective study that involved 49 patients treated with palliative chemotherapy between January 2000 and December 2010. Factors included: age, gender, performance status, metastatic diagnosis onset (at diagnosis or later); specific metastatic sites, number of metastatic localizations, response to chemotherapy, and hemoglobin rate., Results: In univariate analysis, factors associated to a better survival were: metastasis at diagnosis, good performance status, response to chemotherapy and single metastatic site. Independent factors in multivariate analysis were: metastasis at diagnosis and single metastatic site., Conclusion: Our study confirmed many determinants on survival described in the literature.

The Buschke - Lowenstein tumor is a rare sexually transmitted disease. Its location at the anal margin is also very rare. The most incriminated risk factor is human papillomavirus infection. Its clinical form may be confusing with other tumor and infectious lesions. Histologically, it is characterized by a well-differentiated malpighian proliferation. It represents local aggressive behavior. The treatment of reference remains the surgery with healthy margins of excision. Other treatments have been tested, but their effectiveness remains uncertain. We report here a new case of anal margin Buschke - Lowenstein tumor with a review of the literature.

Introduction: Pediatric high grade gliomas are rare tumors of the central nervous system. Treatment is multidisciplinary, comprising surgical excision followed by radiotherapy and/or chemotherapy., Objectives: describe these tumors' characteristics as seen in our institution, and identify factors associated with better overall survival., Patients and Methods: We conducted a retrospective study of 30 cases of pediatric high grade glioma treated consecutively in our institution over a 20-year period. Brainstem tumors and patients aged more than 22years were excluded. Univariate analysis was conducted to determine factors associated with better overall survival., Results: The series comprised 30 pediatric high grade gliomas: 27 glioblastomas and 3 anaplastic astrocytomas. The sex ratio was 1.7. Mean age was 13years. Tumors were mainly located in the cerebral hemispheres (63.3%). Median tumor size was 5cm. Glioblastomas were subdivided into 26 cases of classical subtype (96.3%) and 1 case of epithelioid subtype (3.7%). Surgical strategy consisted in tumor resection in 24 cases (80%). Twenty-one patients (70%) received postoperative radiotherapy. Therapeutic response at end of treatment was complete in 7 cases (23.3%). Postoperative radiation therapy and complete treatment response were significantly associated with improved overall survival in all high grade gliomas and also specifically in glioblastomas (P<0.001 and P=0.005, respectively)., Conclusion: Our results suggest that postoperative radiotherapy and complete treatment response are predictive factors for better overall survival in pediatric high grade glioma., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

A method modifying a vacuum-assisted UV micro-molding (VAUM) process is proposed for the fabrication of polymer two-level submicron high porosity membranes (2LHPM). The modified process allows for the fabrication of robust, large-area membranes over 5 × 5 cm2 with a hierarchical architecture made from a 200 nm-thick layer having submicron level pores (as small as 500 nm) supported by a 20 μm-thick layer forming a microporous structure with 10-15 μm diameter pores. The fabricated freestanding membranes are flexible and mechanically robust enough for post manipulation and filtration of cell samples. Very high white blood cell (WBC) capture efficiencies (≈97%) from healthy blood samples after red blood cell (RBC) lysis are demonstrated using a 3D-printed filter cartridge incorporated within these 2LHPM. A high release efficiency of ≈95% is also proved using the same setup. Finally, on-filter multistep immunostaining of captured cells is also shown.

Purpose: We report in this study, the dosimetric and carcinologic results of intensity-modulated technique for the reirradiation of nasopharyngeal carcinomas., Patients and Methods: Eight patients reirradiated with intensity-modulation technique between January 2015 and December 2017 were included. We noted for each patient: the minimum, maximum and average doses, the dose received by 95% (D95%), 98% (D98%) and 2% (D2%) of the volume to be irradiated, the homogeneity and conformity indices and doses to the organs at risk., Results: Target volume coverage was satisfactory with a median of D95% greater than 57Gy (95% of the prescribed dose). The median maximum dose received by the spinal cord and brainstem were 8.2Gy and 18.25Gy, respectively. After a median follow-up of 14.5 months [1-29 months], five patients were in complete remission of their disease. Overall survival at 2 years was 66.7%. An increase in preexisting late toxicity after the first irradiation (now grade 2 or above) was found in four patients (50% of cases)., Conclusion: Intensity-modulation is an attractive technique for reirradiation of the nasopharynx. It allows a better conformity of the dose to the target and a reduction of the doses on the already irradiated critical organs. This offers good control of the disease with fewer severe late toxicities., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: We aimed to evaluate therapeutic results of radiotherapy for gastric mucosa-associated lymphoid tissue (MALT) lymphomas., Patients and Methods: We reviewed retrospectively the records of 11 patients presenting with gastric MALT lymphoma treated between 1993 and 2014. Patients with low-grade lymphoma in failure after helicobacter eradication had exclusive gastric external radiotherapy. Chemotherapy followed by radiotherapy were indicated in case of high grade lymphoma. Radiotherapy doses range between 30 and 40Gy (2Gy per fraction, five fractions per week)., Results: All tumours were IE stage. Seven patients with low-grade lymphoma had radiotherapy. Four patients with high-grade lymphoma received chemotherapy then radiotherapy. Ten patients are in complete remission after treatment achievement. Five and 10 years disease-free survival are 100%. No severe toxicity was seen., Conclusion: Eradication of Helicobacter pylori is the mainstay of treatment of gastric MALT. External irradiation is an effective and well-tolerated treatment modality in case of resistance to helicobacter eradication., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Tuberculosis (TBC) is a major public health problem with high mortality especially in developing countries. It is associated with a higher risk of developing pulmonary and non-pulmonary malignancies including solid and hematologic cancers. Association between TBC and nonpulmonary malignancies is rarely described in the literature., Aim: To describe the epidemiological, clinical, therapeutic modalities and the evolutive aspects of patients treated for cancer and TBC., Methods: This is a retrospective study conducted over a period of 19 years (between 1993 and 2012), including 10 patients followed up for cancer and tuberculosis at the department of oncology and the department of infectious disease, CHU Habib Bourguiba Hospital and CHU HediChaker, Sfax, Tunisia., Results: The average age of patients was 55 years old. The sex ratio was 1. The different locations of cancer were represented by the breast (4 cases), the nasopharynx (1 case), the colon (1 case), the kidney (1 case) the gum (1 case), the endometrium (1 case) and the blood (1 case).TBC and cancer were synchronous in 5 cases. Concerning the metachronous presentation that interested 5 patients, the average time betweenthe onset of TBC after cancer diagnosis was 3.5 years. Three of these patients were treated by chemotherapy with radiation therapy. TBClocalization was nodal in 6 cases, spinal one case, nasopharyngeal in one case, peritoneal in one case and urogenital in one case. The diagnosisof TBC was made incidentally in two cases during axillary lymph node dissection. The therapeutic management of cancer was based on surgery,chemotherapy and / or radiotherapy. All patients received anti TBC treatment for at least six months. Surgery was indicated in one case(laminectomy). A complete remission of cancer was observed in 9 patients. Concerning TBC, recovery was observed in 8 patients, 1 patient hada spinal recurrence and 1 patient is being treated., Conclusion: Chronic inflammation during TBC can lead to cancer development. The etiopathogenesis of this association is still imperfectly known. Association between TBC and non-pulmonary cancer, although rare, should be always kept in mind in order to handle in time these two diseases in order provide the best chances of recovery for patients.

Purpose: A retrospective study to evaluate the efficacy and safety of the addition of neoadjuvant chemotherapy to concurrent chemoradiotherapy in the treatment of nasopharyngeal carcinoma., Patients and Methods: Data from 62 patients treated for non-metastatic nasopharyngeal carcinoma were analyzed by comparing two groups of patients: a first group of 32 patients treated with 3 cycles of neoadjuvant chemotherapy based on docetaxel, cisplatin and 5-fluoro-uracil every 21 days followed by concurrent chemoradiotherapy (weekly cisplatin 40mg/m 2 with radiotherapy 70Gy, 2Gy per session, 5 sessions per week) and a second group of 30 patients treated with the same concurrent chemoradiotherapy., Results: After a median follow-up of 53.5 months, neoadjuvant chemotherapy showed a significant reduction in the rate of a distant metastatic relapses (3.3% vs. 10%, P=0.03). No significant difference in disease-free survival at 5 years (65.6% vs. 68.8%, P=0.46) or overall survival at 5 years (68.8% vs. 73.3%, P=0.46) was noted between the two groups. Induction chemotherapy was associated with febrile neutropenia of 15.6%. During concurrent chemoradiotherapy, hematological complications were greater in the first chemotherapy group (53% vs. 33%)., Conclusion: Induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil is a safe and effective option in the treatment of nasopharyngeal carcinoma. A better definition of high risk of relapse group would optimize the indications of this chemotherapy in the therapeutic arsenal., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)