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It is now well-acknowledged that microbiota has a profound influence on both human health and illness. The gut microbiota has recently come to light as a crucial element that influences cancer through a variety of mechanisms. The connections between the microbiome and cancer therapy are further highlighted by a number of preclinical and clinical evidence, suggesting that these complicated interactions may vary by cancer type, treatment, or even by tumor stage. The paradoxical relationship between gut microbiota and cancer therapies is that in some cancers, the gut microbiota may be necessary to maintain therapeutic efficacy, whereas, in other cancers, gut microbiota depletion significantly increases efficacy. Actually, mounting research has shown that the gut microbiota plays a crucial role in regulating the host immune response and boosting the efficacy of anticancer medications like chemotherapy and immunotherapy. Therefore, gut microbiota modulation, which aims to restore gut microbial balance, is a viable technique for cancer prevention and therapy given the expanding understanding of how the gut microbiome regulates treatment response and contributes to carcinogenesis. This review will provide an outline of the gut microbiota's role in health and disease, along with a summary of the most recent research on how it may influence the effectiveness of various anticancer medicines and affect the growth of cancer. This study will next cover the newly developed microbiota-targeting strategies including prebiotics, probiotics, and fecal microbiota transplantation (FMT) to enhance anticancer therapy effectiveness, given its significance., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2023.)

There is mounting evidence for the emerging role of gut microbiota (GM) and its metabolites in profoundly impacting allogenic hematopoietic stem cell transplantation (allo-HSCT) and its subsequent complications, mainly infections and graft versus host-disease (GvHD). The present study was performed in order to investigate changes in GM composition and fecal metabolic signature between transplant patients ( n = 15) and healthy controls ( n = 18). The intestinal microbiota was characterized by NGS and gas chromatography-mass spectrometry was employed to perform untargeted analysis of fecal metabolites. We found lower relative abundances of Actinobacteria, Firmicutes, and Bacteroidetes and a higher abundance of Proteobacteria phylum after allo-HSCT. Particularly, the GvHD microbiota was characterized by a lower relative abundance of the short-chain fatty acid-producing bacteria, namely, the Feacalibacterium , Akkermansia , and Veillonella genera and the Lachnospiraceae family, and an enrichment in multidrug-resistant bacteria belonging to Escherichia , Shigella , and Bacteroides . Moreover, network analysis showed that GvHD was linked to a higher number of positive interactions of Blautia and a significant mutual-exclusion rate of Citrobacter . The fecal metabolome was dominated by lipids in the transplant group when compared with the healthy individuals ( p < 0.05). Overall, 76 metabolites were significantly altered within transplant recipients, of which 24 were selected as potential biomarkers. Furthermore, the most notable altered metabolic pathways included the TCA cycle; butanoate, propanoate, and pyruvate metabolisms; steroid biosynthesis; and glycolysis/gluconeogenesis. Specific biomarkers and altered metabolic pathways were correlated to GvHD onset. Our results showed significant shifts in gut microbiota structure and fecal metabolites characterizing allo-HSCT.

Breast cancer (BC) is the most common form of cancer among women worldwide. Despite the huge advancements in its treatment, the exact etiology of breast cancer still remains unresolved. There is an increasing interest in the role of the gut microbiome in modulating the anti-cancer therapeutic response. It seems that alteration of the microbiome-derived metabolome potentially promotes carcinogenesis. Taken together, metabolomics has arisen as a fascinating new omics field to screen promising metabolic biomarkers. In this study, fecal metabolite profiling was performed using NMR spectroscopy, to identify potential biomarker candidates that can predict response to neoadjuvant chemotherapy (NAC) for breast cancer. Metabolic profiles of feces from patients ( n = 8) following chemotherapy treatment cycles were studied. Interestingly, amino acids were found to be upregulated, while lactate and fumaric acid were downregulated in patients under the second and third cycles compared with patients before treatment. Furthermore, short-chain fatty acids (SCFAs) were significantly differentiated between the studied groups. These results strongly suggest that chemotherapy treatment plays a key role in modulating the fecal metabolomic profile of BC patients. In conclusion, we demonstrate the feasibility of identifying specific fecal metabolic profiles reflecting biochemical changes that occur during the chemotherapy treatment. These data give an interesting insight that may complement and improve clinical tools for BC monitoring.

The mechanical of the tricalcium phosphate matrix sintered with different amounts of the magnesium oxide have been investigated. The tricalcium phosphate - magnesium oxide composites were characterized by using the mechanical properties such as rupture strength, Vickers hardness and elastic modulus. The effects of the sintering process on the structural changes of the composites were investigated. At 1300 °C, the highest performance was obtained for the tricalcium phosphate containing 5 wt% MgO. The maximum mechanical strength and Young's modulus of the composites reached 9 MPa and 38 GPa, respectively. The result can be explained by the formation of both, liquid phase, which helps to fill the pores in the microstructure, and a new phase relative to the calcium magnesium phosphate. At 1400 °C and beyond 5 wt% MgO, the performances of the composites are hindered by the intragranular porosity formation and by the exaggerated grain growth. The addition of the magnesium oxide to the tricalcium phosphate matrix promotes the reduction of the wear rate and the friction coefficient. The composites performances are close to the enamel., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Currently, a marked number of clinical trials on cancer treatment have revealed the success of immunomodulatory therapies based on immune checkpoint inhibitors that activate tumor-specific T cells. However, the therapeutic efficacy of cancer immunotherapies is only restricted to a small fraction of patients. A deeper understanding of key mechanisms generating an immunosuppressive tumor microenvironment (TME) remains a major challenge for more effective antitumor immunity. There is a growing evidence that the TME supports inappropriate metabolic reprogramming that dampens T cell function, and therefore impacts the antitumor immune response and tumor progression. Notably, the immunosuppressive TME is characterized by a lack of crucial carbon sources critical for T cell function and increased inhibitory signals. Here, we summarize the basics of intrinsic and extrinsic metabolic remodeling and metabolic checkpoints underlying the competition between cancer and infiltrating immune cells for nutrients and metabolites. Intriguingly, the upregulation of tumor programmed death-L1 and cytotoxic T lymphocyte-associated antigen 4 alters the metabolic programme of T cells and drives their exhaustion. In this context, targeting both tumor and T cell metabolism can beneficially enhance or temper immunity in an inhospitable microenvironment and markedly improve the success of immunotherapies.

The sintering of the tricalcium phosphate with different percentages of titania was investigated. The samples were characterized by differential thermal analysis, dilatometry analysis, X-Ray diffraction, infrared spectroscopy, magic angle scanning nuclear magnetic resonance and scanning electronic microscopy measurements. The samples were examined by using the mechanical properties such as rupture strength, Vickers hardness and elastic modulus. The sintering of the tricalcium phosphate-titania composites indicates the evolution of the microstructure, the densification and the mechanical properties. The performances of the composites increase with both the sintering temperature and the addition of the titania. The highest values of the composites of rupture strength (33 MPa), Vickers hardness (270 Hv), Young׳s modulus (33.1GPa) and shear modulus (15.7 GPa) were obtained after the sintering process with 40 wt% titania at 1200 °C. The increase of these performances is due to the formation of the liquid-phase which helps to fill the pores in the microstructure. Above 40 wt% TiO2, the mechanical properties of the composites are hindered by the exaggerated grain growth formation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The objective of this study was to determine the effect of the content of titania and the sintering process on the transformation phase, the densification, the rupture strength and the microstructures of the alumina-10 wt.% tricalcium phosphate composites. After the sintering process, the samples were examined by using (31)P and (27)Al magic angle scanning nuclear magnetic resonance, X-ray powder diffraction and scanning electron microscopy analysis. The Brazilian test was used to measure the rupture strength of the samples. The present results provide new information about solid-state reactivity in the ternary system α-alumina-β-tricalcium phosphate-anatase-titania. The differential thermal analysis of the α-alumina-β-tricalcium phosphate-titania composites shows two endothermic peaks, at 1360 °C and at 1405 °C, which are caused by the reactions between titania/alumina and titania/tricalcium phosphate, respectively. Thus, the presence of titania in the alumina-10 wt.% tricalcium phosphate leads to the formation of β-Al2TiO5 at 1360 °C. At 1600 °C, the alumina-10 wt.% tricalcium phosphate-5 wt.% titania composites displayed the highest rupture strength (74 MPa), compared to the alumina-10 wt.% tricalcium phosphate composites (13.5 MPa). Accordingly, the increase of the rupture strength is due to the formation of the new β-Al2TiO5 phase., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Intramedullary spinal cord metastases are extremely rare and affect 0.1 to 0.4% of all cancer patients. We report the case of intramedullary metastases in a 42-year-old patient, 12 months after the initial diagnosis of a lung adenocarcinoma. The patient was on third-line chemotherapy for a progressive disease with node and bone metastases. He complained of weakness and difficulty walking. The MRI permitted confirmation of the diagnosis. Corticotherapy was started and the patient underwent radiotherapy. A targeted therapy was indicated. The patient died three months after the initiation of this treatment. The aim of this paper is to report a new case of intramedullary spinal cord metastases from a pulmonary adenocarcinoma, focus on its rarity and diagnostic and therapeutic difficulties through a review of the literature., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Although genetic susceptibility to nasopharyngeal carcinoma (NPC) has been recognized for a long time, little is known about the responsible genes. X-Ray repair cross-complementing protein 1 (XRCC1) and human 8-oxo-guanine glycosylase 1 (hOGG1) genes are involved in deoxyribonucleic acid (DNA) repair and were found associated with NPC risk in three Asian case-control studies. The objective of the present study was to test these genes in a sample from North Africa, one of the major NPC endemic regions in the world. Three single nucleotide polymorphisms (SNPs) in the XRCC1 gene and one SNP in the hOGG1 gene were genotyped in 598 NPC cases from Morocco, Algeria, and Tunisia and 545 controls frequency matched by recruitment center, age, sex, and urban/rural household. The genotype and allelic distributions for the hOGG1 (326)Ser/Cys SNP and for the XRCC1 (399)Arg/Trp, (280)Arg/His, and (194)Arg/Trp SNPs did not differ significantly among NPC cases and controls. The XRCC1 (194)Trp allele frequency was significantly lower in the North African population than in Asian population (f = 0.04 vs. 0.31 in Cantonese Chinese and 0.21 Han Chinese). The hOGG1 (326)Ser allele frequency was significantly higher in the North African population (f = 0.73) than in Asian populations (f = 0.39 in Taiwanese). The results of the present study obtained from a large sample indicate that the XRCC1 and hOGG1 genes are unlikely to play a role in the susceptibility to NPC in North Africans. Our results do not corroborate those found in Asian population on smaller samples., (Copyright ©2011 Wiley-Liss, Inc.)

Cervical cancer is the second most common cancer among Tunisian women, and the incidence rates vary by region. Three Tunisian registries report age-standardized rates of 6.3/10(5) in the central region, 5.4/10(5) in the north, and 2.7/10(5) in the south. High-risk human papillomavirus (HPV) types and their variants differ in carcinogenic potential and geographic distribution. The HPV type and variant distribution could be a factor in the differing rates between regions of Tunisia. Tumor tissue was collected from 142 Tunisian cervical cancer patients. Demographic and reproductive characteristics of the patients were abstracted from cancer registry and hospital records. HPV type and variant analyses were performed using PCR-based Luminex and dot-blot hybridization assays. Eighty-three percent of tumors were infected with at least one HPV type. European variants of HPV16/18 were the most prevalent in tumors from all three regions, with all HPV18 infections and 64% of HPV16 infections being of European lineage. A higher frequency of HPV16 was present in Northern Tunisia (80%) than in Central (68%) or Southern Tunisia (50%) (P=0.02). HPV18/45 was significantly more common in adenocarcinomas (50%) than in squamous cell carcinomas (11%) (P=0.004). Frequent infection with European HPV variants most likely reflects the history of European migration to Tunisia. In addition to the importance of understanding the variants of HPV in Tunisia, behavioral and cultural attitudes towards screening and age-specific infection rates should be investigated to aid the development of future vaccination and HPV screening programs and policies., (Copyright © 2011 Wiley-Liss, Inc.)

Background: Around 20% of breast cancers (BC) show ERBB2 gene amplification and overexpression of the ERBB2 tyrosine kinase receptor. They are associated with a poor prognosis but can benefit from targeted therapy. A better knowledge of these BCs, genomically and biologically heterogeneous, may help understand their behavior and design new therapeutic strategies., Methods: We defined the high resolution genome and gene expression profiles of 54 ERBB2-amplified BCs using 244K oligonucleotide array-comparative genomic hybridization and whole-genome DNA microarrays. Expression of ERBB2, phosphorylated ERBB2, EGFR, IGF1R and FOXA1 proteins was assessed by immunohistochemistry to evaluate the functional ERBB2 status and identify co-expressions., Results: First, we identified the ERBB2-C17orf37-GRB7 genomic segment as the minimal common 17q12-q21 amplicon, and CRKRS and IKZF3 as the most frequent centromeric and telomeric amplicon borders, respectively. Second, GISTIC analysis identified 17 other genome regions affected by copy number aberration (CNA) (amplifications, gains, losses). The expression of 37 genes of these regions was deregulated. Third, two types of heterogeneity were observed in ERBB2-amplified BCs. The genomic profiles of estrogen receptor-positive (ER+) and negative (ER-) ERBB2-amplified BCs were different. The WNT/β-catenin signaling pathway was involved in ER- ERBB2-amplified BCs, and PVT1 and TRPS1 were candidate oncogenes associated with ER+ ERBB2-amplified BCs. The size of the ERBB2 amplicon was different in inflammatory (IBC) and non-inflammatory BCs. ERBB2-amplified IBCs were characterized by the downregulated and upregulated mRNA expression of ten and two genes in proportion to CNA, respectively. IHC results showed (i) a linear relationship between ERBB2 gene amplification and its gene and protein expressions with a good correlation between ERBB2 expression and phosphorylation status; (ii) a potential signaling cross-talk between EGFR or IGF1R and ERBB2, which could influence response of ERBB2-positive BCs to inhibitors. FOXA1 was frequently coexpressed with ERBB2 but its expression did not impact on the outcome of patients with ERBB2-amplified tumors., Conclusion: We have shown that ER+ and ER- ERBB2-amplified BCs are different, distinguished ERBB2 amplicons in IBC and non-IBC, and identified genomic features that may be useful in the design of alternative therapeutical strategies.

Tricalcium phosphate and synthesized fluorapatite powder were mixed in order to elaborate biphasic composites. The samples were characterized by X-ray diffraction, differential thermal analysis, infrared spectroscopy, scanning electron microscopy and by an analysis using (31)P nuclear magnetic resonance. The sintering of tricalcium phosphate with different percentages of fluorapatite (13.26 wt%; 19.9 wt%; 33.16 wt% and 40 wt%) indicates the evolution of the microstructure, densification and mechanical properties. The Brazilian test was used to measure the rupture strength of the sintered biphasic composites. The mechanical properties increase with the sintering temperature and with the addition of fluorapatite additive. The mechanical resistance of beta tricalcium phosphate-33.16 wt% fluorapatite composites reached its maximum value (13.7 MPa) at 1400 ( composite function)C, whereas the optimum densification was obtained at 1350 ( composite function)C (93.2%). Above 1400 ( composite function)C, the densification and mechanical properties were hindered by the tricalcium phosphate allotropic transformation and the formation of both intragranular porosity and cracks. The (31)P magic angle spinning nuclear magnetic resonance analysis of composites as sintered at various temperatures or with different percentages of fluorapatite reveals the presence of tetrahedral P sites.

Background: The lifestyle risk factors for nasopharyngeal carcinoma (NPC) in North Africa are not known., Methods: From 2002 to 2005, we interviewed 636 patients and 615 controls from Algeria, Morocco and Tunisia, frequency-matched by centre, age, sex, and childhood household type (urban/rural). Conditional logistic regression was used to evaluate the association of lifestyles with NPC risk, controlling for socioeconomic status and dietary risk factors., Results: Cigarette smoking and snuff (tobacco powder with additives) intake were significantly associated with differentiated NPC but not with undifferentiated carcinoma (UCNT), which is the major histological type of NPC in these populations. As demonstrated by a stratified permutation test and by conditional logistic regression, marijuana smoking significantly elevated NPC risk independently of cigarette smoking, suggesting dissimilar carcinogenic mechanisms between cannabis and tobacco. Domestic cooking fumes intake by using kanoun (compact charcoal oven) during childhood increased NPC risk, whereas exposure during adulthood had less effect. Neither alcohol nor shisha (water pipe) was associated with risk., Conclusion: Tobacco, cannabis and domestic cooking fumes intake are risk factors for NPC in western North Africa.

Objective: A multicenter, open-label, phase 2 study evaluated the efficacy and safety of intravenous vinflunine as third-line treatment in patients with progressing metastatic breast cancer (MBC) after failure of anthracycline- and taxane-based chemotherapy., Patients and Methods: Fifty-six patients with MBC, relapsing after receiving 2 previous treatments for advanced disease, including both anthracyclines and taxanes, received 320 mg/m(2) of vinflunine once every 3 weeks (median number of 2.5 cycles, range: 1-13)., Results: According to an independent radiologist, the response rate was 12.5% (95% CI: 5.2-24.1) and 14% (95% CI: 5.3-27.9) (6 partial responses) in the treated and evaluable populations, respectively. Disease control was achieved in 42.9% and 51.2% of the patients, respectively. Median progression-free survival was 2.6 months (95% CI: 1.6-4.0 months) with a median overall survival of 11.4 months (95% CI: 7.4-14.2 months). Duration of response was 6.8 months (95% CI: 5.6 months, upper limit not reached). Leukopenia was the most frequent hematologic toxicity, with grade 3/4 severity in 49.1% of the patients. Grade 3 neutropenia in 30.9%, grade 4 in 40.0% of patients, febrile neutropenia (5.4%), and 1 case of neutropenia infection (1.8%) were reported. Other grade 3 toxicities included anemia (5.5%), fatigue (14.3%), and constipation (7.1%), which were noncumulative. The adverse events associated with vinflunine were predictable and manageable., Conclusions: Vinflunine is an active and well-tolerated agent as third-line treatment of patients with MBC after failure of anthracycline- and taxane-based therapy. These results warrant further investigation of vinflunine monotherapy or in combination for the treatment of MBC.

Aim: The aim of this study is to evaluate the implication of BRCA1 gene and the mitochondrial micro satellite (situated between 303 and 315 positions) mutations in the occurrence of breast cancer in Tunisia., Methods: Nine Tunisian patients with hereditary breast cancer have been analyzed. For each patient, total genomic DNA was extracted and used as a template for the amplification of 24 exons of the BRCA1 gene and an hyper variable mitochondrial region. The obtained products were purified and automatically sequenced., Results: The results revealed five types of mutations for the micro satellite situated between the 303 and 315 positions and two deleterious BRCA1 mutations for two unrelated patients which present the same mitochondrial mutation (315.insC) suggesting his implication in the modulation of the BRCA1 deleterious mutations penetrance.

The goal of this study is to analyze certain epidemiologic characteristics of breast cancer in Tunisia and to foresee the consequences that will arise from the trends in incidence of this cancer. Data obtained from the North-Tunisia Cancer Registry (NTCR) and from the Salah AZAIZ Institute (SAI) Registry is used to estimate the different incidence rates and to compare these rates with those of other countries. In 15 years the crude incidence rate for breast cancer in the North Tunisia almost doubled to reach 21.5 cases/100,000 women per year during 1994-1998. The high rate of this cancer among women younger than 35 years (11%) could be related to a relatively low incidence among post-menopausal women. The clinical profile of breast cancer remains quite alarming: 40.2% of cases have a tumor with a clinical diameter equal or greater than 5 cm. Birth cohort effect, also know as the generation effect, is expected to lead to an increase of cancer incidence in the future. The rather high number of young cases is a source of additional cost on social and financial level. The priority is now to solve the problem of late diagnosis it has aggravated the prognosis of this cancer in Tunisia.

Background: To reduce tobacco smoking is, in Tunisia, a public health priority. The tobacco cessation consultation is one of the interventions to fight against the tobacco epidemic; it is a new activity developed in the Salah-Azeiz Tunis cancer centre. The objective of this work is to evaluate the impact of the consultation on the smokers after one year of activities and to analyse the prognostic factors of tobacco cessation in order to improve the efficacy of such an activity in the future, in Tunisia., Methods: The cessation methods were based on cognitive and behavioral therapies associated with nicotine patch, delivered free of charge. During one year (July 2003 to June 2004), 340 smokers were attended. Data on their smoking status and psychological characteristics were collected using a standardized questionnaire., Results: The patients were mostly men (79%), these smokers did not present important anxiety-depressive troubles, 68% thought that they were able to quit easily. The majority (57%) smoked more than 20 cigarettes a day and was nicotine-dependent (Fagenström >7). Half of this population had already intended to stop, they declared to smoke mostly because of stress. The global cessation rate after a median follow-up of 32 weeks is 27%. The cessation rate lasting six months for 83 patients followed regularly was 23%. The good prognostic factors of cessation, after multivariate analysis, were (when taking out from the model the regular follow-up), to be confidant on the possibility to stop (OR=0.87 [0.78-0.97]). On the contrary, a high score (>7) for Fagerström test (OR=1.9 [1.1-3.4), the use of smoking to fight against stress (OR=1.08 [1.0-1.2) and a smoking environment at home (OR=4.5 [1.1-18.9]) were prognostic of a failure in quitting smoking., Conclusion: These results show that the cessation rate, which is still too low as compared with the literature, could be increased by a better follow-up of smokers associated with an information campaign on the existing possibilities to quit smoking in Tunisia.

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the development of hundreds to thousands of adenomatous polyps in colon and rectum. The APC gene (adenomatous polyposis coli) is considered as the major mutated gene in FAP. It has been shown that biallelic germline mutations in the base-excision-repair gene MYH can be responsible for a recessive inheritance of adenomatous polyposis (AP). This study is the first Tunisian genetic analysis on AP patients. Multiplex ligation-dependent probe amplification (MLPA) was used to screen the APC gene for large genomic rearrangements. The total APC and MYH exon sequences and exon-intron edges were sequenced in an effort to detect germline mutations, four were explored. Mutations were detected in four patients that fulfil the clinical criteria of AP. Three mutations were found in the APC gene, of which two were novel (c.1636&#95;1639delAGTG and c.2514 G>T) and all gave rise to a truncated APC protein. The missense G382D mutation, already described in north and south European populations was found in the MYH gene at the homozygous state in the fourth patient with moderate AP. Our preliminary study provides a basis for implementation of genetic counselling for AP.

Background: This study aimed to identify prognostic factors for outcome in Tunisian patients with nonmetastatic inflammatory breast cancer (IBC) receiving multimodality therapy., Patients and Methods: From 1994 to 2000, 100 patients with nonmetastatic IBC were reviewed. Patients underwent neo-adjuvant chemotherapy including anthracyclines (99%), then mastectomy (93%) when feasible, radiotherapy (83%) and adjuvant chemotherapy (84%). Sixty patients (60%) had hormone therapy., Results: Median age at diagnosis was 44 years (range 23-71). Seventy patients had premenopausal status (70%). Ten cases occurred during pregnancy (10%). Body mass index indicated overweight or obesity in 76 patients (76%). After neo-adjuvant chemotherapy, pathologic complete response (pCR) rate was 20%. Median time of follow-up for surviving patients was 44 months. Median progression-free survival (PFS) was 19 months and overall survival (OS) 30 months. Factors associated with improved survival were no pregnancy (P = 0.0095), estrogen receptor positivity (P = 0.028), tumor size <5 cm (P = 0.021), clinical complete response (cCR) (P = 0.022), pCR (P = 0.011), negative nodes (P = 0.053) and hormone therapy (P < 0.001). In multivariate analysis, cCR, negative nodes and hormone therapy were independently associated with better OS and PFS. Factors predictive to pCR were age >45 years, negative nodes and cCR., Conclusions: Tunisian patients with IBC have particular epidemiologic characteristics, with earlier disease and context of overweight and obesity, but prognostic factors are similar to those reported in the literature. Hormone therapy seems to improve patient outcome.

North Africa is one of the major Nasopharyngeal Carcinoma (NPC) endemic regions. Specific food items unique to this area were implicated to be associated with NPC risk, but results were inconsistent. Here we have performed a large-scale case-control study in the Maghrebian population from Tunisia, Algeria and Morocco. From 2002 to 2005, interviews were conducted on 636 cases and 615 controls. Controls were hospitalized individuals from 15 non-cancer hospital departments, or friends and family members of non-NPC cancer subjects, matched by center, childhood household type (rural or urban), age and sex. Conditional logistic regression is used to evaluate the risk of factors. In results, consumption of rancid butter, rancid sheep fat and preserved meat not spicy (mainly quaddid) were associated with significantly increased risk of NPC, while consumption of cooked vegetables and industrial preserved fish was associated with reduced risk. Other foods such as fresh citrus fruits and spicy preserved meat (mainly osban) in childhood, industrial made olive condiments in adulthood, were marginally associated. In multivariate analyses, only rancid butter, rancid sheep fat and cooked vegetables were significantly associated with NPC. In regard to possible causative substances, our results implicate the involvement of butyric acid, a potential Epstein-Barr virus (EBV) activator.

Purpose: Inflammatory breast cancers (IBC) have specific immunophenotypic profiles as compared to non-inflammatory (non-IBC): combined differential expression of estrogen receptor, Ki67, E-cadherin, MUC1, and ERBB2 can be used as an IBC signature. It is thought that IBC occurs with a high frequency in Tunisia. The aim of this study is to evaluate this signature on a Tunisian series., Methods: The expression of five proteins (E-cadherin, ERBB2, estrogen receptor, Ki67, MUC1) was studied by immunohistochemistry on a consecutive series of 91 cases of IBC (T4D) treated at Tunisian Salah Azaiz Institute (ISA) and deposited in a tissue microarray (TMA). Results were compared to the same study on a series of 85 cases treated in France., Results: The ISA cases were characterized by a significantly younger age of patients (median: 42 years old in ISA for 53.5 in IPC, p=0.00042) and a higher frequency of invasive micropapillary pattern. None of the five parameters was expressed differentially in the two series. In non-metastatic patients, high level of proliferation (Ki67) and overexpression of ERBB2 were associated with poor outcome., Conclusion: The IBC from Tunisia were not different from those observed in France on the basis of IHC profiles. However, the younger age of the patients suggest a specific epidemiological context that should be investigated.

BRCA1 is a tumor suppressor gene which is inactivated by mutation in familial breast and ovarian cancers. Over 300 different disease causing germ-line mutations have been described; 60% are unique to an individual family. This diversity and the large size of the gene lead us to search for a prescreening method for BRCA1 mutations. Since BRCA1 is a nuclear protein in normal cells, but reported by some authors to be cytoplasmic in breast tumor cells of patients with BRCA1 mutation, we evaluated immunohistochemistry as a prescreening technique to identify BRCA1 mutations in patients with familial presentation of breast cancer. Using a monoclonal antibody against the carboxy-terminal region of BRCA1, we performed immunohistochemistry on 18 tumor samples from patients with hereditary breast cancer. Cytoplasmic staining of BRCA1 was observed in 10 cases. Of the 18 tumors, 12 (66%) showed either BRCA mutation or BRCA1 accumulation or both, indicating that BRCA1 function might be lost in breast tumor cells not only through mutation, but also via abnormal cytoplasmic location. The immunohistochemical test used in this study would not be efficient as a pre-screening method of deleterious mutations, but it appeared useful to investigate tumor physiology.

We estimated survival rate at 9 years of all (470) women with breast cancer diagnosed at Salah Azaïez Institute of Cancer in Tunis to identify the main prognosis factors. Data were collected on residence, socioeconomic level, circumstances of discovery of the tumour, histological type, tumour size, presence of metastases, extension of the tumour, treatment and survival. Comparison of survival curves was done with Log Rank test. Cox model was used for multivariate adjustments and calculation of the hazard ratio (HR) (relative risk of death). There was a survival rate of 61% at 5 years and of 51% at 9 years. Tumour size >5 cm was significantly associated with lower survival as was capsular rupture. After stratification for tumour size and age, only surgery and radiotherapy were significantly associated with improved survival.

Hereditary breast cancer accounts for 3-8% of all breast cancers, with mutations in the BRCA1 and BRCA2 genes responsible for up to 30% of these. To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, we studied 36 patients who had at least one first degree relative with breast and/or ovarian cancer Thirty-four 34 patients were suggestive of the BRCA1 mutation and two were suggestive of the BRCA2 mutation, based on the presence of male breast cancer detected in their corresponding pedigrees. Four mutations in BRCA1 were detected, including a novel frame-shift mutation (c.211dupA) in two unrelated patients and three other frameshift mutations--c.4041delAG, c.2551delG and c.5266dupC. Our study is the first to describe the c.5266dupC mutation in a non-Jewish Ashkenazi population. Two frameshift mutations (c.1309del4 and c.5682insA) were observed in BRCA2. Nineteen percent (7/36) of the familial cases had deleterious mutations of the BRCA1 or BRCA2 genes. Almost all patients with deleterious mutations of BRCA1 reported a family history of breast and/or ovarian cancer in the index case or in their relatives. Our data are the first to contribute to information on the mutation spectrum of BRCA genes in Tunisia, and we give a recommendation for improving clinical genetic testing policy.

Background: In developing countries, continuing medical education (CME) is lacking and physicians' knowledge of cancer control may also be lacking., Method: We evaluated knowledge of 144 primary care physicians in Egypt and 50 in Tunisia regarding breast cancer (BC) and inflammatory BC (IBC) in particular. We invited the physicians to pretesting, presentation of an educational module, and post-testing., Results: We found significant improvement in knowledge about risk factors for IBC and BC, importance of early detection and clinical examination, and referral of IBC cases. The variables that were independently associated with improved BC knowledge, were rural practice location, being a female physician, and greater numbers of BC patients seen in the last year. CONCLUSION. We developed and evaluated a CME module to improve BC diagnostic knowledge of primary care physicians in developing countries. The evaluation showed that physicians most lacking in this knowledge had the greatest gains. With the anticipated adoption of this module in Egypt and Tunisia, we expect to see more appropriate referrals to cancer centers. These results could guide future oncology CME for physicians in developing countries.

HLA system plays a key role in the tumor cells' escape from immune surveillance. Herein is the first report on the correlation of the susceptibility to breast cancer with HLA class II markers in Tunisia. Molecular typing of HLA-DRB1 and -DQB1 loci was undertaken for 70 Tunisian female patients. Comparison of allele and haplotype distribution between patients and 70 female control subjects reveals a negative association between HLADRB1* 07-DQB1*02 and the incidence of breast cancer in the Tunisian population.

Jerba Island, located in South Eastern Tunisia, is inhabited by four ethnic groups: Berbers, Arabs, sub-Saharans, and Jews. All live in distinct areas, although the Arabs are also distributed all over the island. The first Arab settlement was founded in the 7th century A.D., so co-existence with Berbers has lasted for more than a millennium. Religious and cultural differences have represented an obstacle to the intermixing of these groups, and among both Arabs and Berbers marriages usually occur between members from the same extended family. Using new mtDNA data and previously described Y-chromosome STR-defined haplotypes, we tested whether this reported inbreeding would be reflected in the differentiation between Berber and Arab communities. Concerning mtDNA, the Berber group presented a greater Eurasian contribution (87%), and, surprisingly, no U6 haplotypes were found; in contrast, the Arabs showed a larger contribution of sub-Saharan lineages (24%) and the U6 haplogroup amounted to 10%. Another source of evidence for the reproductive isolation of the two groups was revealed through the analysis of haplotype matching (both mtDNA and Y-chromosome), showing that matching probabilities between them is of the same order of magnitude of that observed when contrasting samples from different European countries., (Am. J. Hum. Biol. 18:149-153, 2006. (c) 2005 Wiley-Liss, Inc.)

We report a case of epithelioid hemangioendothelioma observed in soft tissue in a 35-year-old man who presented a painful mass of the right arm which progressed in size for two years. Imaging revealed a 7-cm poorly limited expansive tumor process located in the medial muscle compartment of the right arm. Surgical resection was performed. Histological and immunohistochemical examination led to the diagnosis of soft tissue epithelioid hemangioendothelioma. The tumor recurred in the right arm and the right axillary fossa with development of multiple nodules in the contralateral thoracic wall and pleural effusion. Adjuvant chemotherapy and radiotherapy were performed, but the patient died at two years.

Background: Metastases to the breast are rare and can be missed without knowledge of the clinical history. We report an unusual breast metastasis originating in an olfactory neuroblastoma., Case: A breast metastasis from esthesioneuroblastoma occurred in a 20-year-old woman 2 years after the onset of the disease. The aspirates were hypercellular and composed of cellular aggregates and single cells with a monomorphic appearance. The cytoplasm was scanty and inconspicuous. The nucleus was large, with granular, hyperchromatic chromatin. Mitoses and apoptotic bodies were numerous. Because we were unaware of the past history at the time of the cytologic analysis, a definitive diagnosis was made only after pathologic study., Conclusion: Esthesioneuroblastoma metastatic to the breast must be considered in the differential diagnosis of breast metastases. Fine needle aspiration, in conjunction with clinical information, can be effective in the diagnosis of esthesioneuroblastoma metastatic to the breast.

This is a retrospective study of patients treated for cervix cancer staged IB2, IIA or IIB with bulky tumor (> 4cm). Treatment was concurrent radiotherapy (45Gy with 1,8Gy daily fraction) and chemotherapy (5 cycles of Platinum 40mg/m2/week). All patients underwent Brachytherapy (15Gy on the reference isodose according to Paris system) followed by surgery (radical abdominal hysterectomy and bilateral pelvic lymphadenectomy: Piver 3) Between October 1999 and December 2002, forty five patients were treated in this protocol. Median age was 46 years (21- 68). Histology was squamous cell carcinoma in 93% and glandular carcinoma in 7%. Average external radiation dose was 44Gy (20-50). Ninety three percent of patients had at least 3 cycles of chemotherapy and 46,5% received the planned 5 cycles. On the operative specimens, there was 62,5% complete response and only 7 pelvic node involvement (17,5%). Four postoperative complications were noted (one vascular injury, one urinary fistula, one phlebitis and one lymph collection). Preoperative combined radiotherapy and chemotherapy in the early bulky stages of uterine cervix cancer is well tolerated and "gives" a high rate of sterilisation. There was no increase in surgical morbidity.

Background: This study was undertaken to determine epidemiological and pathological profile of cervical cancer in Tunisia., Design Study: Registration and analysis of all cervical cancer newly diagnosed during the year 1994 (year of general census) based on review of all pathology laboratory files in the country with exclusion of previously diagnosed cases according to clinical data., Results: During the year 1994, 216 new cases were registered among which 195 cases (89.81%) were invasive carcinoma. The standardized incidence (invasive cancer) is 5.91 per 100000 women per year. The average age was 53.7 year. Sixty-three percent cases are diagnosed at an advanced stage (IIB, III, IV FIGO stages). Invasive carcinoma has distributed as follows: 177 cases (91.23%) were squamous invasive carcinoma, 17 cases (8.77%) were invasive adenocarcinoma. In the same year, 21 cases of in situ squamous carcinoma were registered with an average age equal to 44.21 year. Only one case of cervical cancer was a sarcoma (0.52%)., Conclusion: The incidence of cervical cancer in Tunisia is relatively low in spite of the absence of a screening program. This may be related to monogamy and observance of legal age of marriage. Squamous invasive carcinoma is the most frequent pathological type., Condensation: The incidence of cervical cancer in Tunisia is relatively low in spite of the absence of a screening program.

It was previously shown that letrozole (Femara) was significantly more potent than anastrozole (Arimidex) in inhibiting aromatase activity in vitro and in inhibiting total body aromatisation in patients with breast cancer. The objective of this study was to compare letrozole (2.5 mg per day) and anastrozole (1 mg per day) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with an anti-oestrogen. This randomised, multicentre and multinational open-label phase IIIb/IV study enrolled 713 patients. Treatment was for advanced breast cancer that had progressed either during anti-oestrogen therapy or within 12 months of completing that therapy. Patients had tumours that were either positive for oestrogen and/or progesterone receptors (48%) or of unknown receptor status (52%). The primary efficacy endpoint was time to progression (TTP). Secondary endpoints included objective response, duration of response, rate and duration of overall clinical benefit (responses and long-term stable disease), time to treatment failure, and overall survival, as well as general safety. There was no difference between the treatment arms in TTP; median times were the same for both treatments. Letrozole was significantly superior to anastrozole in the overall response rate (ORR) (19.1% versus 12.3%, P=0.013), including in predefined subgroups (receptor status-unknown, and soft-tissue- and viscera-dominant site of disease). There were no significant differences between the treatment arms in the rate of clinical benefit, median duration of response, duration of clinical benefit, time to treatment failure or overall survival. Both agents were well tolerated and there were no significant differences in safety. These results support previous data documenting the greater aromatase-inhibiting activity of letrozole and indicate that advanced breast cancer is more responsive to letrozole than to anastrozole as second-line endocrine therapy.

Unlabelled: Our objective is to compare clinical and biological presentation of patients with bone metastatic disease., Patients and Methods: We collected prospectively 60 patients (adults and children) with proven bone metastasis. Tumors are mainly breast cancer (25/60) or nasopharyngeal carcinoma (8/60). All 8 children presented all with abdominal neuroblastoma. Bone lesions are lytic in 85% of cases. ALP and LDH seem to be sensitive markers for bone mestatasis with 75% and 80% pathologic rates. The highest rates have been observed in patients with multiple bones lesions (> 8) and painful metastases (more than 7 in the VAS). The median survival was 8 months (3 to 54)., Conclusion: Even conventional, some biochemical markers as ALP and LDH remain useful in the diagnosis and prognosis in patients with proven bone metastasis.

This national survey aims to evaluate opioid availability and prescription by pharmacists in Tunisia and to examine pharmacists' attitude regarding Tunisian law. We surveyed a sample of 300 pharmacists randomly selected from the National Council of Pharmacists list and using the random table. This study started in September 1999 by sending to pharmacists a confidential questionnaire asking about the importance, the rate of sale and the availability of analgesics in their pharmacy. It also tried to determine pharmacists' opinions regarding Tunisian law. A total of 157 pharmacists out of 300 responded to the survey (52 per cent), 95 per cent were working in pharmacies and 15 per cent in hospitals. Analgesics were estimated to be important to very important in their work in 84 per cent and less important in 16 per cent of cases. They were given under advice with great importance in 85 per cent of cases and with less importance in 15 per cent of cases. Analgesic self-medication was frequent in 95 per cent of cases and rare in 4 per cent of cases. Analgesics of levels 1 and 2 were often to always available in 97 per cent of cases and rarely available in 1.5 per cent of cases. Some 84.7 per cent of pharmacists had opioid supplies and 8.9 per cent had no opioids in stock and 6.4 per cent hadn't given a response. 30 per cent of pharmacists think that the 7 days law for opioid prescription should be modified and 66 per cent think it should not, fearing illicit use, fraud and dependance. Pharmacists think that the minimal list of opioids to be stocked in a pharmacy is sufficient because of low demand.

Secondary tumours to radio- and/or chemotherapy have rarely been reported after treatment for head and neck cancers. We report a case of mandibular fibrosarcoma observed 7 years after chemoradiotherapy for undifferentiated nasopharyngeal carcinoma in a patient treated when 20 years old.

Objective: To evaluate the insertion and use of implantable central venous accesses in medical oncology at the Institute Salah Azaïz., Methods: From January 1992 to June 2000, 205 patients including 179 adults (118F/61M) and 26 children aged 7 months to 72 years (mean 37 years) required the insertion of an implantable port (IP). Tumoral pathology was dominated by metastatic breast carcinoma (93/179), digestive cancer (42/179) and paediatric cancer (26 cases)., Results: Excluding 3 initial failures, we inserted 205 IP for 202 patients. The supraclavicular anatomic way (Yoffa) was used in 156/205 cases and the subclavicular (Aubaniac) for the resting 32 cases with a jugular conversion in 17 cases. Initial complications were represented by 6 arterial puncture (2.9%), 3 pneumothorax (1.5%) and 1 catheter migration in the right pulmonary artery. Median life duration of the material was 210 days (3 to 1460 days) for adults and 185 days (3 to 1460 ays) for children. Mean life duration for the 205 IP was 240 days +/- 239 (3 to 1460 days) with a total of 49,200 IP-days. We explanted 17 IP for infection (8 cases), cutaneous ulceration (8 cases) and actinomycin extravasation (1 case). We observed 6 cases (2.9%) of subclavian and jugular thrombosis treated by anticoagulants and conservation management of the port. Presently, 58 patients are alive with IP in place., Conclusion: Implantable ports represent a useful option in medical oncology for patients treated with prolonged chemotherapy and adjuvant treatments such as antibiotics, transfusion. This method allows a good comfort for the patients and also the treating team but requires a prealable training for the nursing team.

Since the few data exploring a possible association between Epstein-Barr virus (EBV) and breast cancer are conflicting, we investigated this association together with the influences of geographical areas. 509 breast cancers were sampled from areas with varying risks of nasopharynx carcinoma (NPC) such as North Africa (Algeria and Tunisia, high-risk area); southern France (Marseille, intermediate-risk area); and northern Europe (northern France, the Netherlands and Denmark; low-risk areas). Polymerase chain reaction (PCR) of a subregion of EBV BamHIC encoding the EBERs demonstrated that 31.8% of the tumours contained the viral genome. No significant differences were observed among the geographical areas. However, positive samples showed higher loads of the EBV genome in the NPC high- and intermediate-risk areas than in the low-risk areas. EBV type 1 was the dominant strain. In situ hybridization studies using a(35)S-labelled riboprobe for EBER1 and a laser capture microdissection, combined with quantitative PCR, showed that EBV localization was restricted to some tumour epithelial cell clusters. EBV could not be detected in the stroma. Considering the whole population covered, the presence of the EBV genome was not correlated with age, menopausal status, tumour, size, nodal status or histological grade., (Copyright 2001 Cancer Research Campaign.)

Hodgkin's disease is now curable in more than 50% of cases, due to its chemo- and radio-sensitivity. However, treatment exposes to a risk of secondary cancer varying from 1 to 10% depending on chemoradiotherapy doses and schedules. We report a case of secondary breast cancer associated with a secondary thyroid cancer observed in a 24-year-old man treated when he was 13 years old by vinblastin and radiation for stage IIA, a Hodgkin's disease.

Background: Nasopharyngeal carcinoma is a common cancer in Tunisia with an estimated incidence of 1.8/100,000. The tumor shows a characteristic association with paraneoplastic syndromes., Case Reports: We report three cases of histologically proven dermatomyositis associated with nasopharyngeal carcinoma in patients aged 40, 24 and 65 years. In all cases, the course of the paraneoplastic syndrome ran parallel to the nasopharyngeal carcinoma., Discussion: Dermatomyositis is one of the numerous paraneoplastic syndromes associated with nasopharyngeal carcinoma. Systematic examination of the nasopharynx is required in case of dermatomyositis.

We report the results of a prospective Tunisian study using primary chemotherapy followed by conservative surgery in primitive limb osteosarcoma. From January 1988 to January 1998, 56 patients affected by limb osteosarcoma entered in a prospective study of neoadjuvant chemotherapy with the T10 protocol before surgery with a conservative intent. Initial work-up include: clinical exam with tumor measurements, chest and limb X-rays, limb CT-scan or MRI, chest CT-scan, bone scintigraphy and hematological and renal biological exams. Patients receive pre- and post-operative chemotherapy according to the T10 modified protocol. Fifty-six patients (33 M/23 F) with a mean age of 19 years (8 to 28) are included. Mean clinical and radiological tumor size is around 14 cm. Main histologic type is classic osteosarcoma (50% of cases) and 10 patients (9%) presented with initial metastasis; 42 patients on 56 receive the whole pre-operative protocol. Treatment is well tolerated excluding 18 episodes of mucositis, 29 of leucopenia (< grade 3), 7 of thrombopenia (< grade 3), 4 of cutaneous toxicity, 2 of pulmonary toxicity and 3 of nausea-vomiting. We observe 36% of good histological responders and 64% of bad responders to primary chemotherapy, 27 patients on 49 operated (53%) have a conservative surgery and 18 (47%) a radical surgery. With a median follow-up of 51 months (8 to 128), 29 patients remain alive free of disease (15/17 GR and 14/30 BR), 2 are alive with disease, 2 died by toxicity, 14 died by progressive disease and 9 are lost to follow-up with evolutive disease. Five year disease-free survival is 55% for the 46 non metastatic patients. In univariate analysis, seric alkaline phosphatase level (p = 0.0014) and histological response to chemotherapy (p = 0.0218) are significant factors for prognosis.

Objective: To report the results of seric neuron specific enolase in pediatric neuroblastoma., Patients and Methods: Our retrospective study concerns 21 children treated in our institution from 1992 to 1998 for neuroblastoma. Seric NSE was determined by immunoenzymology technique at different stages of the disease and the treatment., Results: Mean value for the 39 dosages of the whole patients was 127.9 ng/ml with a sensitivity of 56%, five patients has presented normal values. Mean value for the 18 patients in stage IV was 132.38 ng/ml. We also observed in 3 patients, an evolution of the seric NSE parallel to this of the disease under chemotherapy., Conclusion: NSE represents a moderate sensitive and specific tumor marker for pediatric neuroblastoma. However, it represents a good value in prognosis and follow-up after chemotherapy.

In spite of the progress of the imagery in ophthalmology, the retinoblastoma remains in some particular cases, difficult to make. Moreover, the therapy sanction is often heavy. The lactate dehydrogenase (LDH) dosage in aqueous humor is an invasive technique conceivable when there are diagnosis problems particularly in retino-blastoma of old children and in affections simulating retino-blastoma. The purpose of this work is to lay out three observations where the LDH dosage enabled to keep the retinoblastoma diagnosis in one 8-year old child and eliminate it in two children having pseudoglioma with spontaneous evolution allowing to confirm the non-tumoral nature of the affection. Thus, the technique of LDH dosage has been reliable for the 3 cases which we have introduced. The authors compare the reliability of the different cytochemical techniques during the retinoblastoma diagnosis.

Primary gastric MALT non-Hodgkin's lymphoma is rare in immunocompetent children. To our knowledge, only two cases have been previously described. We report two cases of gastric MALT lymphoma associated with Helicobacter pylori. Clinico-pathological features are similar to those observed in adults. The relationship between the microbial infection and non-Hodgkin's lymphoma development is discussed.

Jerba is an island situated in the South-East of Tunisia were some ethnic groups (Arabs, Berbers, Blacks, Jewishs and others) cohabit for centuries. The religion and cultural differences have represented an obstacle to a mixture between these groups. In order to evaluate the genetic differentiation between the muslim groups (Arabs, Berbers and Blacks), we have analysed the polymorphism of a mitochondrial DNA coding region. The cytochrome oxydase coding region (COII) was amplified by PCR in 57 Arabs, 42 Berbers and 16 Blacks. The amplified products were analysed by Restriction Fragment Length Polymorphism (RFLP). Genetic distances were calculated by using the AMOVA program. The values of these distances were significantly different between Arabs and Blacks, and between Berbers and Blacks but not between Arabs and Berbers. So That, to refine the evaluation of genetic diversity between Arabs and Berbers, we have analysed the polymorphism of a second mitochondrial coding region which encodes for the fifth unit of NADH deshydrogenase (ND5). Eleven haplotypes were defined from the resulting data of mitochondrial COII and ND5 polymorphism and a significant genetic distance between Arabs and Berbers was computed.

Secondary tumours after radio and/or chemotherapy are mainly of hematopoietic (acute non lymphoblastic leukemia, non-Hodgkin lymphoma) or soft tissue lineage previously described most frequently after breast cancer and Hodgkin disease treatment with radio and/or chemotherapy. We report two cases of classical osteosarcoma's observed 9 and 3 years after treatment for UCNT with combined radiotherapy and alkylant-based adjuvant chemotherapy in one case and exclusive loco-regional irradiation in the second case.