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We aimed to review all published literature reporting biological data about inflammatory breast cancer (IBC) in populations from North Africa. Methods: We reviewed all studies that evaluated biological features of IBC in six North African countries between 1990 and 2017. Among 118 screened studies, 13 were included, none about Mauritania/Libya. Results: Across the studies, hormonal receptors were positive in 46–69% of cases, reaching 83% in Algeria. HER2 was overexpressed in 25–39% of cases. Recombinant human C protein expression was the highest in Egyptian patients (87%) compared with other North African populations. Using mRNA expression recombinant human C protein was expressed in 83% of Tunisian patients. WISP3 gene expression showed positive immunohistochemistry staining in 17% and mRNA expression in 26.8% of IBC. Conclusion: Biological aspects of IBC across North Africa show important similarities and differences.

Resume Les carcinomes epidermoides (NPC) sont frequemment indifferencies de type UCNT (undifferentiated carcinoma of nasopharyngeal type) et ont une incidence variable, intermediaire pour le Maghreb et le Bassin mediterraneen, tres elevee pour l’Asie du Sud-Est et faible (

Glioblastoma (GB) is the most common and lethal primary brain tumor in adults representing 25% of primary brain tumors in adults. The objective of our study was to report the epidemiologic, clinical and therapeutic features of GB in Tunisia.Our retrospective study included 41 patients with histologically confirmed GB treated between 2006 and 2012 at the medical oncology departments of Abderrahmane Mami hospital in Ariana and the military hospital in Tunis.Median age was 54 years (13 to 72 years) and sex-ratio was 2.3. Karnofsky performance status (KPS) was70% in 31.7% of cases, while Recursive partitioning analysis radiation therapy oncology group (RTOG-RPA) classification was III in 11 (26.8%), IV in 19 (46.3%), V in 10 (24.3%) and VI in 1 (2.4%) cases. Complete resection (CR) was achieved in 29 patients (70.7%), partial resection (PR) or tumor debulking in 5 patients (12.2%) and biopsy alone (BA) in 7 patients (17.1%). All patients received brain radiotherapy (RT) at a dose of 60 Gy combined with concurrent temozolomide (TMZ). Nineteen patients (46.3%) received adjuvant TMZ, 8 of them completed 6 cycles. Median overall survival (OS) was 12 months (2 to 56 months). Six, 12, 18 and 24-months OS rates were 84.6%, 57.6%, 35.4% and 20.7%, OS being correlated to age, KPS, RPA and quality of resection.Our retrospective study is the first African GB series. Despite it included predominantly poor prognosis patients with impaired neurocognitive function and adjuvant treatment discontinuation, our median OS was comparable to Stupp.

Lung cancer is the first cause of death by cancer worldwide. In Tunisia, its incidence has increased from 17.6 cases per 100.000 persons in 1997 to 27.6 cases per 100.000 persons in 2003. Its prognosis has been improving thanks to the emergence of molecular targets. The first one is represented by EGFR (Epidermal growth factor receptor), which marks this (2014) its tenth anniversary. many other targets have been identified. the most famous and useful of them the fusion gene ALK-EML4 but other oncogenic pathways have been implicated and under investigations including HER2, BRAF, MET, RET... The relevant challenges encountered are represented by the difficulty to achieve a consensual decisional and therapeutic algorithm, the absence of standardized diagnostic techniques and unavoidable occurrence of secondary resistance due to the activation of other oncogenic pathways that must be explored and targeted. In this update, we tried to present the major pathways implicated and the most relevant practice routine strategies.

Exocrine pancreatic carcinoma (EPC) occurs in the majority of cases with early locoregional spread and distant metastasis at diagnosis, leading to dismal prognosis and limited treatment options. Traditional cytotoxic chemotherapy provide only modest benefit to patients with EPC. Identification of different molecular pathways, overexpressed in pancreatic cancer cells, has provided the opportunity to develop targeted therapies with a crucial therapeutic role in this cancer setting.Our aim is to study the epidemiological, clinicopathological characteristics, treatment modality and clinical outcome of pancreatic adenocarcinoma in Tunisian patients treated in the department of medical oncology Abderrahmane Mami Ariana.This retrospective study concerned patients with exocrine pancreatic carcinoma treated between 2009 and 2012. We analysed the following data: Anamnesis, age, sex, delay to diagnosis(DD), symptoms, clinical exam, performance status, stage, therapeutic protocol and results.We collected 158 patients (113 males/45 females, SR 2.5) with a median age of 64 years (20-93). The median DD was 2 months (1-12). Abdominal pain, jaundice and weight loss were the most frequent symptoms, 88.6%, 43% and 55.1% of cases respectively. Performance status was2 in 56.9% (90 pts). Seric CA19-9 was increased in 86.6% of cases. Tumor was at stage III in 24.7% and stage IV in 58.2%. Surgery was done in 24.7% of cases (39pts), curative in 21 patients. Neoadjuvant chemotherapy(NACT) was administrated to 10.8% of patients, adjuvant to 13.9% (22 pts) and palliative chemotherapy(PCT) concerned 58.8% of patients. We used weekly Gemcitabine, Gemcitabine-CDDP, Gemcitabine-Oxaliplatine and LV5-FU2-CDDP in palliative setting respectively in 20%, 31.1%, 2.2 and 36.7% of cases. Median survival was 6 months (2-60) and the 1year overall survival at 38.8%.EPC remains a rare cancer in Tunisia. The prognosis is still grim worldwide and so does in our country. In this retrospective serie, we noted the predominance of locally advanced and metastatic cases with a long delay to diagnosis. Awareness campaigns have to be programmed to improve early diagnosis in EPC and improve outcomes.

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

The occurrence of a lung cancer is a consequence of a long-lasting process dealing with a transformation of a normal cell to a malignant one. The four steps of transformation reflect the genetic modifications of the cells. The molecular studies of pre-invasive lesions have already established a correlation between the lesion continuum and the multi-step carcinogenesis. Gradual genetic alterations are correlated with the increase of the cell's malignant potential. We tried to present the carcinogenesis of the lung non microcellular carcinomas and to highlight the main therapeutic targets.

Objective The purpose of this study was to evaluate the outcome of patients with cervical adenocarcinoma and to determine the characteristics and the prognostic factors of this entity. Study design This retrospective study was done in the Department of Surgical Oncology of the Salah Azaiz Institute of Tunis with 79 cases of invasive adenocarcinoma of the uterine cervix that were collected from 1990 to 1999. Survival was analyzed according to the Kaplan-Meier method. Univariate analysis of prognostic factors was performed with the test of log rank. Cox regression model was used in multivariate analysis of prognostic factors. Results Mean age was 50 years, and metrorrhagia was mostly revealing in 73% of the cases. Early stages (I, IIa, IIb with 1/3 proximal parametrial invasion) and "pure" type adenocarcinoma were found in 78% and 87% of the cases, respectively. Treatment consisted of a radiosurgical combination in 52 cases; exclusive radiotherapy was practiced with 17 patients. The 5 year-overall and disease-free survival percentages were, respectively, 68% and 72.4%. Poor prognostic factors were age >50 years, tumor size >4 cm, advanced stage, tumor grade, and lymph nodes and lymph-vascular space involvement. With the use of multivariate analysis, only stage and lymph node metastases remained significant prognostic factors. Conclusion This report shows survival and prognostic factors that are similar to those found in previous studies, but unlike the Western countries, our results demonstrate a high rate of early stages and no increase in frequency of cervical adenocarcinoma.

Nasopharyngeal carcinoma (NPC) represents an interesting model in the field of head and neck cancers. This cancer is rare in occidental countries (

Resume Introduction Les metastases oculaires affectent electivement l’uvee et, en particulier, la choroide. Les metastases papillaires ont ete exceptionnellement decrites et ne representent que 5 p. 100 des localisations oculaires metastatiques. Nous rapportons dans cette observation un cas de metastase papillaire chez une patiente atteinte d’un adenocarcinome d’origine inconnue. Observation Une femme, âgee de 37 ans, suivie et traitee depuis 4 mois par chimiotherapie pour adenocarcinome d’origine inconnue metastatique a la plevre et a l’os, consulta pour une baisse importante de l’acuite visuelle de l’œil gauche avec cephalees et vomissements. L’examen du fond de l’œil gauche notait l’existence d’une lesion papillaire jaunâtre avec œdeme papillaire associee a un decollement sereux retinien peripapillaire inferieur. La fluoroangiographie retinienne objectivait des lesions choroidiennes evocatrices de metastases. Le scanner X cerebro-orbitaire revelait la presence de metastases cerebrales. La patiente est decedee 4 mois apres le diagnostic de la metastase oculaire et 8 mois apres celui de l’adenocarcinome. Conclusion Devant toute lesion papillaire, le diagnostic de metastase papillaire doit etre evoque, meme en l’absence d’antecedent carcinologique connu. Les tumeurs carcinomateuses, en particulier celles du sein et du poumon, representent les causes les plus frequentes de metastases papillaires. Les adenocarcinomes d’origine inconnue comparativement aux syndromes lympho- et myeloproliferatifs restent une cause exceptionnelle de neuropathie optique metastatique.

Xeroderma pigmentosum Variant (XP-V) form is characterized by a late onset of skin symptoms. Our aim is the clinical and genetic investigations of XP-V Tunisian patients in order to develop a simple tool for early diagnosis. We investigated 16 suspected XP patients belonging to ten consanguineous families. Analysis of thePOLHgene was performed by linkage analysis, long range PCR, and sequencing. Genetic analysis showed linkage to thePOLHgene with a founder haplotype in all affected patients. Long range PCR of exon 9 to exon 11 showed a 3926 bp deletion compared to control individuals. Sequence analysis demonstrates that this deletion has occurred between two Alu-Sq2 repetitive sequences in the same orientation, respectively, in introns 9 and 10. We suggest that this mutationPOLHNG_009252.1: g.36847_40771del3925 is caused by an equal crossover event that occurred between two homologous chromosomes at meiosis. These results allowed us to develop a simple test based on a simple PCR in order to screen suspected XP-V patients. In Tunisia, the prevalence of XP-V group seems to be underestimated and clinical diagnosis is usually later. Cascade screening of this founder mutation by PCR in regions with high frequency of XP provides a rapid and cost-effective tool for early diagnosis of XP-V in Tunisia and North Africa.

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

Lung cancer represents a major public health problem.It represents the first cause of mortality by cancer in Tunisia. Its incidence reaches 40% of lung cancers. Its clinical, radiologic and molecular aspects have been improved inducing the necessity of a new classification which will consider the necessity of a multidisciplinary management.To highlight the new classification of lung adenocarcinomas and to present the major recommendations.We tried to present the main recommendations of the American Thoracic Society and the European Respiratory Society of lung adenocarcinoma.This new classification identifies pre-invasive lesions represented by in-situ adenocarcinoma (the ancient bronchioloalveolar), the micro-invasive adenocarcinoma and invasive adenocarcinoma. The latter have been divided in sub-types according to the predominant architectural features. Thus, three groups of invasive adenocarcinoma with presumed different prognoses have been identified: the lepidic predominant adenocarcinoma which has a good prognosis, the micro-papillary and solid predominant adenocarcinomas which have a bad prognosis and the papillary and acinar adenocarcinomas which have an intermediate prognosis. All these entities have specific diagnostic features and criteria. These recommendations are available for biopsies and surgical resected specimen.The new classification of lung adenocarcinoma puts emphasis on the necessity of a multi-disciplinary management of these tumors in order to improve their prognosis. It identifies new entities with different prognoses that could justify specific modalities of treatment and follow up.

The use of regimens with adjuvant taxanes reduces the risk of recurrence and improves survival in patients with node-positive breast cancer, but the use of taxanes in node-negative breast cancer is still to be defined. The aim of this study is to evaluate the role of taxanes in high-risk node-negative breast cancer. Two categories of studies were reviewed: studies that evaluated both node-positive and node-negative breast cancers, and studies that included only high-risk node-negative breast cancers. Three phase-III studies that evaluated both negative and positive nodes did not show any benefit of the use of taxanes according to the node-negative subgroup analyses, versus two studies (European Cooperative Trial in Operable Breast Cancer [ECTO] et Grupo Español de Investigación del Cáncer de Mama [GEICAM]) that showed a significant difference in disease-free survival. In view of these studies, the role of taxanes in node-negative breast cancer is still controversial and the results of the ongoing trials may respond to this subject.

The abnormalities of the haemoglobin divide into qualitative abnormalities and quantitative abnormalities. This variant contains polymorphisms often useful as markers of population. At present more than 693 types of abnormal haemoglobin are listed. This hemoglobinopathies can arise at reached subjects of cancerous pathologies.To bring to report association hémoglobinopathies-cancers.Our study was realized to the Institute Salah azaiz (ISA) concerning hémoglobinopathies in carcinologic environment over a period spreading out of May 2004 in February 2008. The phenotypic and biochemical study of haemoglobin revealed the presence of 328 carriers of abnormalities of the haemoglobin on a total of 10550 patients followed to ISA. 7 types of abnormalities of the haemoglobin were identified (HbS, Hb C, Hb O arab, Hb D, Hb G, fast mutant and ß thalassemia.The sickle cell line represents the most wide-spread hémoglobinopathie (51.3 %). 48.2 % of the carrier subjects of abnormalities of the haemoglobin are followed for malignant pathologies. Among these hemoglobinopathies, we revealed the presence of two fast mutants of the haemoglobin corresponding to the haemoglobin Bangkok. This type of rare mutant is described for the first time in Tunisia. According to the genotypic study by these two cases, the haemoglobin Bangkok results from the replacement at the level of the chain ß some aspartic acid by the wisteria, further to a transfer at the level of the codon 56. A phenotypic study family revealed the presence of similar transfers at certain members of the family.Our work allowed us to notice a relatively important frequency of rare abnormalities of the haemoglobin at patients presenting varied tumoral processes.

To analyze the litterature data concerning the results of the main international randomized trials of adjuvant Aromarase Inhibitors (AI) in adjuvant setting for early breast cancer and the impact on daily practice in the management of breast cancer.We selected through a litterature review 30 publications concerned the topic of AI RESULTS: They concerned the large ATAC, BIG, MA17 and IES concerning anastrozole, letrozole and exemestane . AI have been compared to tamoxifen in upfront of swich intents and showed a superiority to reduce, mortality rate, controlateral breast cancer risk, a better tolerance profile compared to tamoxifen and a sigificant benefit in term of disease-free survival. These results made a revolution in the adjuvant BC treatment, leading to the systematic use of upfront AI in menopaused patients.Adjuvant hormonotherapy in menopaused patients is now based on AI and proved its superiority to tamoxifen in term of distant, controlateral risks reduction and disease-free survival, less for overall survival.

e12016Background: Early onset breast cancer ( ≤ 40 years, EOBC) have a particular aggressive phenotype with a high rate of triple negative (TN) tumors and a worse prognosis. It has also been report...

Small cell carcinoma of the uterine cervix is a rare tumor. It presents clinical and biological features of both cervical neoplasm such as local aggressiveness, and small cell cancer such as early spread and metastases. To date, an effective treatment protocol is not well established. Case: On March 2009, a 44-year-old pregnant woman with small cell carcinoma of the cervix misdiagnosed initially as squamous cell carcinoma, was treated with chemoradiation followed by surgery and brachytherapy. Twenty-three months later, she experienced brain metastases. A metastasectomy lead to an accurate diagnosis. Palliative whole brain radiotherapy was conducted. The patient died of evolutive disease on August 2012. Conclusion: The optimal therapeutic approach of small cell carcinoma of the cervix is still to define. Further studies regarding multimodal treatment are necessary to achieve a significant survival benefit.

The concept of larynx preservation in locally advanced laryngeal or hypopharyngeal squamous cell carcinoma has evolved during the last three decades, especially with the advancement of nonsurgical strategies. These nonsurgical strategies include: (1) radiotherapy alone; (2) concomitant chemoradiotherapy (CCRT); and (3) induction chemotherapy followed by radiotherapy or CCRT and concurrent anti-epidermal growth factor receptor (EGFR). To date, the best approach for larynx preservation has yet to be defined. In this article, we review and discuss important recent randomized phase II/III trials investigating larynx preservation in order to facilitate the selection of an appropriate strategy in the clinical setting. However, the decision of larynx preservation should always be a multidisciplinary approach.

The objective is to report the correlation between pathology and molecular subtype classifications of breast cancer in Tunisian women.This retrospective study concerned data of 966 breast cancer cases collected from 2007 to 2009 at Salah Azaiz Institute of Tunis. These cases were classified by an immunohistochemistry test for estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2) status in the four molecular subtypes, namely luminal A, luminal B, HER2+ and triple negative. The molecular classifications were correlated with the clinicopathological characteristics of the tumors.Luminal A (50.7% of cases) was the most common subtype, with triple negative subtype 22.5%, luminal B 13.4% and HER2+ 13.4%. Triple negative and HER2+ subtypes were significantly associated with large tumor size (5 cm, P 0.001), younger age (40 years, P 0.03) and high grade (P 0.001). Conversely, there was no correlation with the lymph node status.Our data demonstrated that the luminal A subtype, associated with a favorable prognosis, was the most frequent subtype in the Tunisian population; however the triple negative subtype occurred at a high incidence in Tunisia compared to Western countries. The molecular subtypes are correlated to the tumor size, histological grade and patient's age.

Primary small intestinal lymphoma (PSIL) is the second Non-Hodgkin lymphoma (NHL) of the digestive tract (after gastric NHL).To evaluate during the past 28 years the epidemiological, anatomoclinical and therapeutic changes of PSIL in Tunisia through an acquired experience of more than a quarter of a century.Our retrospective study included patients with histologically confirmed small intestinal lymphoma from 1981 to 2008 in Tunisia at Salah Azaiz Institute. The cohort of 210 patients was divided into two groups: A group from 1981 to 1992 (152 patients) and B group from 1993 to 2008 (58 patients). We analysed the epidemiological, anatomoclinical, histological, and therapeutic characteristics.We observed a significant decrease in the annual incidence of PSIL but also a significant transition of diffuse immunoproliferative small intestinal disease (IPSID) also known as "Mediterranean" PSIL, which were progressively replaced by "Western" lymphomas. Laparotomy with or without a debulking surgery, largely performed in group A, has disappeared at the cost of a primary chemotherapy (p0.001). Five-year actuarial global and relapse free survivals were respectively 60.5 and 57.3%.PSIL in Tunisia were subjected to a triple transition: epidemiological, histological and therapeutic.

Trastuzumab is humanized monoclonal antibody targeting her 2 neu receptor, overexpressed in 20% of breast cancers and part of the complex of Epidermal Growth Factor Receptor.To review new advances in the knowledge of the practical use of "trastuzumab (Herceptin ®)" in breast cancer.Review of literature using medical data bases (Medline, Science direct) with the following key words: breast cancer, targeted therapy, HER2 neu, transtuzumab/herceptineTrastuzumab represent an important advance in breast cancer treatment with an improvement of median survival in metastatic setting and overall and disease-free survival in adjuvant setting in association with chemotherapy. Herceptin remain well tolerated with a low and rare risk of cardiac failure.Trastuzumab is a new therapeutic tool very interesting to ameliorate prognosis of breast cancer.

Tobacco smoking is frequent in the world affecting 20 à 50% of the population but with a decrease in occidental countries due to a huge effort based on sensiblisation and anti-tobacco decisions.To review the impact of tobacco on bronchopulmonary affections.A narrative review of literatureIn the next future, yearly tobacco-related deaths could increase from 4.2 millions in 2000 to 10 millions in 2025-2030 making smoking as the main evitable cause of deaths by respiratory diseases. Lung cancer is the leading killer cancer. Tobacco is the most frequent cause of respiratory diseases. It is responsible of 80 to 90% of deaths by chronic obstructive pneumobronchopathiy (COPD) and 80 to 85% deaths by bronchopulmonary cancer.Tobacco is a « chronic disease » necessitating management with advices and medical treatment.

The geopolitical and strategic importance of the Mediterranean area is evident since a long time. In terms of health programs and means for cancer care, significant disparities have been reported between countries that borders the Mediterranean basin. AROME project began modestly in 2006 with a group of leaders who recognized the need to promote practical training of young people and, thus, contribute to reduce these inacceptable inequalities in terms of early diagnosis and management. Moreover, our project has been built from our belief that the socio-cultural specificity of this region, its epidemiology, availability of means for diagnosis and treatment, should impose a sustained regional research and better knowledge of tumor biology and identify the specificities that may require particular strategies of care that should not be based only on Western and Asian research data. We must thus take advantage of advances in the identification of intimate biological tumors to provide answers to our ignorance of the specific Mediterranean biology. In this paper, we illustrate this issue describing some particular cancers in this region such as breast and nasopharyngeal cancers.

Nasopharyngeal cancers are essentially epidermoids (NPC) and dominated by the undifferentiated type (UCNT) in endemic areas. The standard treatment of NPC remain external beam radiotherapy but the results are poor in T3-4 lesions locally advanced (30-40% on event- free survival vs 80-90% in T1-T2) explained by a higher rate of relapse and metastases. Improvement of therapeutic results occurs with addition of chemotherapy to radiotherapy, specially with the concomitant scheme (weekly cisplatin), with an increase of overall and diseasefree survivals for the advanced stages (Meta-analysis data). Despite these progresses, we have to evaluate the risk of long term sequelae of combined therapies in children and adolescents. We are observing however an epidemiologic transition with the increase of more localized cases in term of T and N disease.

Inflammatory breast cancer (IBC) is characterized by a peculiar geographic distribution in incidence, being described as more common in Tunisia and the region of North Africa. The authors performed a systematic review of published literature on rapidly progressing breast cancer and IBC in Tunisia and analyzed the evolution in epidemiology, clinical presentation, treatment, and therapeutic results. They collected, analyzed, and compared all the indexed Tunisian articles about rapidly progressing breast cancer and IBC since the 1970s opening of the Institut Salah Azaiz Institute in Tunis. In the 1970s, rapidly progressing breast cancer diagnosis was based on the Poussee Evolutive classification (1-3). Since the 1990s, IBC diagnosis has been based on the American Joint Committee on Cancer Poussee Evolutive 3/T4d staging. The authors compared the historical data to the most recent publications in terms of epidemiology, clinical features, treatment, and therapeutic results. The most important historical report of rapidly progressing breast cancer concerned 340 patients, representing 58.5% of a cohort of 581 breast cancer patients collected from 1969 to 1974, including 320 (55.2%) with inflammatory signs, 37(6.5%) with Poussee Evolutive 2, and 283 (48.7%) with Poussee Evolutive 3. Subsequent papers have documented a steady decrease in incidence to the current 5% to 7% T4d/IBC. Since the 1970s, Poussee Evolutive in premenopausal woman has increased from 52.5% to 75%; rural predominance has persisted. The 5-year overall survival reached 28% by the year 2000. The authors' analysis demonstrated a trend of decreasing incidence of IBC diagnoses from 50% to presently

Nasopharyngeal carcinomas (NPC) are predominantly of undifferentiated type (UCNT or undifferentiated carcinoma of nasopharyngeal type), rare (1/100,000) and sporadic in occidental countries, but endemic in the Mediterranean area of intermediate incidence (2 to 10/100,000) and highly frequent (10/100,000) in South East Asia. NPC staging is based on TNM UICC 2002 that has a prognostic and therapeutic orientation impact. Irradiation of the primitive tumor and its extensions remains the standard loco-regional treatment. The recent introduction of primary and concomitant chemotherapy leads to an improvement in terms of overall and disease-free survival, specially for for high-risk-patients (T3-4 and N2-3 disease). Prognosis remain linked to T, N, histologic type and quality of response to chemotherapy and radiotherapy.

Introduction Mal de Meleda is a rare form of palmoplantar keratoderma, with autosomal recessive transmission. It is characterized by diffuse erythema and hyperkeratosis of the palms and soles. Recently, mutations in the ARS (component B) gene (ARS, MIM: 606119) on chromosome 8q24.3 have been identified in families with this disorder. Congenital cataract is a visual disease that may interfere with sharp imaging of the retina. Mutations in the heat-shock transcription factor 4 gene (HSF4; MIM: 602438) may result in both autosomal dominant and autosomal recessive congenital cataracts. Case presentation A Tunisian family with two female siblings aged 45 and 30 years, presented with a clinical association of mal de Meleda and congenital cataract. The two patients exhibited diffuse palmoplantar keratodermas. One of them presented with a total posterior subcapsular cataract and had a best corrected visual acuity at 1/20 in the left eye and with the right eye was only able to count fingers at a distance of one foot. The other woman had a slight posterior subcapsular lenticular opacity and her best corrected visual acuity was 8/10 in the right eye and with her left eye she was only able to count fingers at a distance of one foot. A mutational analysis of their ARS gene revealed the presence of the homozygous missense mutation C99Y and two single nucleotide polymorphisms (-55G>C and -60G>C). The splice mutation (c.1327+4A-G) within intron 12 of the HSF4 gene, which has been previously described in Tunisian families with congenital cataract, was not found in the two probands within this family. Conclusion To the best of our knowledge, such original clinical association has not been reported previously. The association of these two autosomal recessive diseases might have occurred in this family due to a high degree of inbreeding. The C99Y mutation may be specific to the Tunisian population as it has been exclusively reported so far in only three Tunisian families with mal de Meleda.

Oral tongue cancer remains an aggressive tumour in Tunisia, and patients often present with locally advanced disease, leading to high mortality. The molecular pathway of its tumorigenesis is not yet understood. This study aimed to assess the biologic significance of p53, heat shock protein 70 (Hsp70), Ki67, and CD34 and their influence on survival in patients with tongue cancer.Archival tissues from 68 patients with squamous cell carcinoma of the tongue were examined for p53, Hsp70, Ki67, and CD34 by immunohistochemistry and correlated with 5-year survival.p53 and Ki-67 were detected in 55% and 77% of tumours, respectively; a significant association between p53 and Ki67 expression was found (p = .038). Forty-seven percent of cases of tongue cancer expressed Hsp70, and only 9% of tumours expressed CD34 angiogenic factor. No significant correlation was noted between survival and expression of p53, Hsp70, Ki67, and CD34 in patients.None of the markers p53, Hsp70, Ki67, and CD34 demonstrated prognostic significance for 5-year survival in patients with squamous cell carcinoma of the tongue.

The epithelioid leiomyosarcoma of the uterine cervix is a rare tumor. Usually, the presenting symptoms are vaginal bleeding and pelvic pain. Surgery is the standard treatment.To present the characteristic of this rare pathology by mean of two cases handled in the Institute Salah Azaiz.Two patients, aged 51 and 42 years, were referred to our institute for vaginal bleeding. Tumors were classified stage II proximal and II distal (FIGO classification modified by Gustave Roussy Institute). The patients had total hysterectomy with pelvic lymph node dissection. Histological exams confirmed the diagnosis of epithelioid leiomyosarcoma of the uterine cervix. Adjuvant external radiotherapy was performed. At 12 and 36 months, the patients are alive with no evidence disease.

Inflammatory breast cancer (IBC) is a clinical diagnosis characterized by a peculiar geographic distribution in incidence, being particularly common in Tunisia and the region of North Africa. The peculiar aspects of the disease in this region may provide some insights on the biological characteristics of the disease. We updated and revised the data from our single-institution experience using the more stringent diagnostic criteria of the International Union Against Cancer (UICC) based on the tumor-node-metastasis (TNM) classification. The new analysis included 419 newly diagnosed cases of IBC evaluated between 1975 and 1996 that were subdivided into three groups: group A (118 cases classified as T4d in 1990-1996); group B (175 cases reported as Pev 2 or 3 in 1975-81 and restaged as T4d); and group C (126 cases classified Pev 2 or 3 in 1975-81 and restaged as T4b). The frequency of IBC cases classified as T4d in the various series was 5.7% for group A (118/2,073) and 13.3% for group B (175/1,317), while T4b represented 9% for group C (126/1,317). The analysis demonstrated worse 5-year overall survival rates for groups A and B (8.5% and 11.3%, respectively) compared to group C (25.6%). Interestingly, using a more uniform classification criteria, the incidence of IBC was 5% to 7% compared to previous historical reports of up to 50% of newly diagnosed cases of breast cancer in Tunisia.

Soluble interleukin-2 receptor alpha (slL-2Ralpha) is a well-known indicator of T-cell activation noted to be increasing in nasopharyngeal cancer. The aims of this study were to evaluate the importance of the use of this marker in nasopharyngeal carcinoma.Our prospective study interested 45 patients (35M/10F) with a mean age of 49 years (15 to 78), presenting a nasopharyngeal carcinoma histologically confirmed and 61 healthy controls. A blood sample was collected from each patient before any treatment, as well as controls to measure sIL-2Ralpha by immunoenzymatic assay. According to the disease status after a period of follow-up ranging from three to 22 months (median 12 months), patients were divided into two groups: The remission group (n=28) represented those with favourable evolution and a second group of 15 patients with unfavourable evolution (2 death, 4 cases of persistent primary disease and 9 patients with distance metastasis). 2 patients were lost to follow-up.serum sIL-2Ralpha levels were significantly higher in patients vs healthy controls (p0.0001). The serum levels correlated with the stage T of NPC (p = 0.01). Patients having a favourable evolution have lower sIL-2Ralpha levels before treatment vs those with unfavourable evolution without statistical difference.Measurement of serum sIL-2Ralpha provides a good estimation of the nasopharyngeal tumor burden. The usefulness of this marker as a parameter to predict prognosis in NPC should be examined further.

Fibroadenoma is a frequent benign breast tumor affecting young woman. The incidence of a carcinoma within adenofibromas is estimated at 0.1 to 0.3%.The purpose of this study was to evaluate the outcome of patients with breast carcinoma arising within adenofibroma and to determine the clinical characteristics and the prognosis of this rare entity.We retrospectively report on four cases of carcinomas arising in mammary fibroadenomas. The mean age was 41 years (26-53). In two cases, fibroadenomas was complex, containing cysts, adenosis and apocrine metaplasia. The adjacent parenchyma contained fibrocystic dystrophy lesions associated in one case to intralobular neoplasia lesions. The treatment consisted of a conservative treatment in two cases and a mastectomy plus axillary node dissection in the two others. Radiotherapy was indicated in all cases and chemotherapy done in three cases. All patients are alive with a mean follow up of 4.25 years (3-7) without any sign of recurrence.Every benign mammary nodule must necessarily be verified surgically to avoid misdiagnosing any carcinomatous area because at this stage its prognosis is better.

Purpose Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer. Lapatinib, an oral reversible inhibitor of epidermal growth factor receptor (EGFR) and human EGFR 2 (HER-2), demonstrated clinical activity in four of five IBC patients in phase I trials. We conducted a phase II trial to confirm the sensitivity of IBC to lapatinib, to determine whether response is HER-2 or EGFR dependent, and to elucidate a molecular signature predictive of lapatinib sensitivity. Patients and Methods Our open-label multicenter phase II trial (EGF103009) assessed clinical activity and safety of lapatinib monotherapy in patients with recurrent or anthracycline-refractory IBC. Patients were assigned to cohorts A (HER-2–overexpressing [HER-2+]) or B(HER-2–/EGFR+) and fresh pretreatment tumor biopsies were collected. Results Forty-five patients (30 in cohort A; 15 in cohort B) received lapatinib 1,500 mg once daily continuously. Clinical presentation and biomarker analyses demonstrated a tumor molecular signature consistent with IBC. Lapatinib was generally well tolerated, with primarily grade 1/2 skin and GI toxicities. Fifteen patients (50%) in cohort A had clinical responses to lapatinib in skin and/or measurable disease (according to Response Evaluation Criteria in Solid Tumors) compared with one patient in cohort B. Within cohort A, phosphorylated (p) HER-3 and lack of p53 expression predicted for response to lapatinib (P < .05). Tumors coexpressing pHER-2 and pHER-3 were more likely to respond to lapatinib (nine of 10 v four of 14; P = .0045). Prior trastuzumab therapy and loss of phosphate and tensin homolog 10 (PTEN) did not preclude response to lapatinib. Conclusion Lapatinib is well tolerated with clinical activity in heavily pretreated HER-2+, but not EGFR+/HER-2–, IBC. In this study, coexpression of pHER-2 and pHER-3 in tumors seems to predict for a favorable response to lapatinib. These findings warrant further investigation of lapatinib monotherapy or combination therapy in HER-2+ IBC.

Undifferentiated carcinoma of nasopharyngeal type (UCNT) is a geographically endemic, Epstein-Barr virus-related carcinoma of epidermoid origin with reported 5-year survival rates of 15%-40% when treated with radiotherapy alone. Although UCNT can be well controlled locally by radiation therapy, in advanced nodal stage N3 [International Union Against Cancer-American Joint Committee on Cancer (UICC-AJCC, 1987)] the survival rate is below 20%, primarily because of metastatic spread in 80% of the fatalities. We report a pilot study of 41 patients with nonmetastatic, locoregionally advanced disease (85% of the patients had a nodal status greater than or equal to N2C-N3; 43% had T4 primaries), during which we used a combination of 100 mg of cisplatin/m2 on day 1, 15 mg of bleomycin by intravenous push and 12 mg/m2 by continuous infusion on days 1-5, and 70 mg of epirubicin/m2 on day 1 every 21 days for three cycles before definitive radiation therapy with 70 Gy for 7 weeks. Twenty-seven of 41 patients (66%; 95% confidence interval = 52.5%-80.5%) achieved a clinical complete response, and 40 of 41 (98%) had a major objective response after chemotherapy. Two deaths were treatment related, but side effects were moderate, and the overall treatment sequence was feasible. At the end of radiation therapy, all 39 assessable patients were in complete response, with a median follow-up of 21+ months (greater than 10-greater than 31); 33 (80%) patients had no evidence of disease. We believe that such a complete response rate in a high-volume disease with the use of combined modality treatment indicates a therapeutic gain in UCNT. Researchers performing a multicenter international controlled trial will test this hypothesis and compare local control, disease-free, and overall survival of the therapeutic sequence presented here with radiotherapy alone.

Carcinoïdes tumours are a rare type of ovarian tumours which anatomoclinical behaviour differs a little from epithelial type.Report of three new cases.We report 3 observations of ovarian carcinoid tumours in patients aged 50, 23 and 28 years. All our patients were operated in emergency for twisting of appendix in two patients and for acute peritonitis in the third one. Treatment was a one-sided salpingo-oophorectomy. The diagnosis of carcinoid tumour was retained on to the definitive histological exam then the patients were re operated to complete the resection.

The aim of this study is the analysis of different epidemiological, clinical, paraclinical and therapeutic aspects of adult granulosa cell tumors of the ovary (AGCT) GCT accounts for 5.7% of all ovarian malignancies. Echography objectives pelvic tumor in all cases. Diagnosis was histological. Primary treatment was exclusively surgically in 11 cases, followed by chemotherapy in 19 cases and radiotherapy in 2 cases. Patients with stage Ia who desire further childbearing can be treated with unilateral adnexectomy. For all other cases, radical surgery followed by chemotherapy for advanced stages and recurrences is the treatment of choice. Prognosis is tightly depending on stage and histologic finding.

primary squamous cell carcinoma (scc) of the thyroid is a rare malignant tumor that needs to be distinguished from other neoplasms. Cases of papillary carcinoma merging in association with squamous cell carcinoma are extremely rare.the characteristics of such association will be studied herein through a review of literature.we report a case of an 87-year-old patient presented with an enlarged right lobe of the thyroid. Thyroid scintigraphy revealed a cold nodule. Clinically, malignancy was suspected. Histopathologic diagnosis was a well-differentiated scc associated with areas of papillary carcinoma. Exhaustive clinical, endoscopic and radiological examinations did not reveal any primary site of scc or any contiguous spread from neighboring structures. Surgery was followed by radiotherapy, but the patient died 6 months later.the coexistence of epidermoide and papillary carcinomas in the thyroid gland must be known because of its prognostic impact.

Angiogenesis is a significant prognostic factor in breast cancer, but the factors that control angiogenesis in vivo are not well defined.The purpose of this study was to investigate P53 expression in breast cancer and to examine the relationship between P53 overexpression and the degree of angiogenesis.A total of 52 paraffin-embedded tumors were evaluated immunohistochemically for expression of P53 and CD34 angiogenesis factor.The majority of P53 positive cases (82%) demonstrated high level of microvessel density (MVD); 18% demonstrated no CD 34 expression. In contrast there was no variation of CD34 expression among P53 negative tumors.This data suggests that microvessel density is promoted by P53 overexpression in breast cancer, and is correlated with high histologic grade.

e12633 Background: To report epidemiologic and anatomo-clinical transition of IBC in Tunisia. Methods: Data including clinico-pathological aspects of 208 cases of T4d or PEV 3 non metastatic breast...

Juvenile granulosa cell tumors of the ovary (JGCTs) are a rare form of neoplasm that makes up less than 5% of ovarians tumors in childhood and adolescence. About 90% are diagnosed in stage I (FIGO) with a favorable prognosis, whereas those at higher stages have a less favorable outecome. The authors describe a juvenile granulosa cell tumor expressed by an early pseudopuberty occurring in a 6 year old child. Clinically, an endocrine syndrome was associated with a pelvic mass. Hyperoestrogenia and serum alphafoetoprotein level were biologically detected. Tumor was localized strictly to the ovary, so conservative surgery was applied and proved sufficient to remove all tumor tissue. Histological examination showed typical microscopic aspect of a juvenile granulosa cell tumor. The patient is well, 14 years after surgery with a normal growth and mental developpment.

Thyroid carcinomas represent the most common endocrine malignancy, and several biological markers are proposed according to the different types of this cancer: for papillary cancer, thyroglobulin constitutes an excellent prognostic factor and rearrangements of ret oncogene can be useful in diagnosis. In sporadic medullary carcinoma, calcitonin is a diagnosis marker of choice, and coupled with ACE, can prevent relapse. Regarding familial medullary carcinoma, mutation screening in ret oncogene leads to early detection of new cases.

The aim of this study was to analyze epidemiology and outcome of 40 patients with gastrointestinal stromal tumor (GIST) expressed CD 117. All epidemiological data (age, sex, location) and survival data were analyzed retrospectively. The tumors occurred in 17 men and 23 women. Stomach was the most common site of localization (47.5%). Of the 37 patients without Gleevec treatment, 18 benignant cases (66.6%) showed long-term survival (2 to 8 years) and 9 malignant cases (33.3%) were diagnosed. 10 cases were still being in followed (2 years). Gastric tumor's survival was better than extragastric tumor's survival without statistically significance (p0.05). Our experience confirms that GIST is an aggressive tumor. 33.33% of them are malignant with recurrence or metastatic potential. Additionnally, epidemiologic factors (age, sex and location) do not have a predictive value.

to evaluate the feasibility, tolerance/toxicity and therapeutic efficacy of 5-fluorouracil (5-FU) by topical application and systemic use, in facial carcinoma associated with XP.This is a prospective study of 10 patients with a median age of 22.9 years and a sex ratio of 4. Tumour lesions were facial mainly in the jugal and temporal region (36%). Chemotherapy indication was discussed in multidisciplinary committee, the topical 5-fluorouracil was applied locally twice a day, whereas the systemic treatment consisted of FUFOL protocol (every 4 weeks a combinaison of a short perfusion of 340 mg/m2 5-FU and preceded by an infusion of 20mg/m2 of folic acid, day 1 to 5); or C-FU protocol, combining continuous infusion of 5-FU (1 g/m2) 5 days associated with cisplatin (100 mg/m2, day 1) every 3 weeks.The median topical treatment duration was of 12 months in 10 patients. We noted a full tumoral regression in 10% of cases. Concerning systemic treatment, the median number of FUFOL cycles was 4 (2 to 6) and we observed a complete response in 6 patients (60%), partial in 2 cases (20%). Treatment was well tolerated in most cases except for the cutaneous irritation on 5-FU application zone and a 4 grade cisplatin otoxicity.Systemic or topical chemotherapy represents an interesting palliative option for facial carcinoma associated with XP, avoiding reiterated surgery and its cosmetic consequences.

Purpose Extra-central nervous system (extra-CNS) metastases are relatively unknown failure patterns in medulloblastoma. The aim of this study was to analyse epidemiological, clinical and aetiopathological aspects of these extra-CNS localisations. Patients and methods Extra-CNS metastases were retrospectively identified in patients treated in the department of radiation therapy at Salah-Azaiz institute (ISA) for medulloblastoma. These metastases were diagnosed as extra-CNS for all secondary localisations not related to other tumour aetiology. Aetiopathological aspects are discussed with a literature review. Results Among 103 patients treated and followed-up in the department of radiation therapy of ISA from 1970 to 1992, 8 developed extra-CNS metastases (7.7%). Age at diagnosis of primitive tumour varied from 3 to 23 years. Sex ratio was 1. Primitive tumour treatment was: complete surgical resection in 4 patients with preoperative cerebrospinal fluid shunting in two, cerebrospinal axis irradiation in 7 patients and a cerebral-limited irradiation in 1. Two patients received chemotherapy for their initial treatment (systemic in one case and intrathecal in the other). The mean free-interval from diagnosis of primitive tumour to extra-CNS metastases was 23 months, varying from 8 to 53 months. These metastases were located in the liver (1 case), cervical lymph nodes (2 cases), bone marrow (1 case) and bone (2 cases). Two patients had multiple metastases: bone and bone marrow (in one), lung, pleura, cervical lymph node and bone localisations (in one). Treatment of these metastases was: chemotherapy in 5 cases, chemotherapy and radiation in one, radiation therapy in one and 2 patients were given only supportive care treatment. All patients died or are in progressive disease in less than one year from the diagnosis of extra-CNS metastases. Conclusion Extra-CNS metastases are not rare and have a poor prognosis. The most commonly involved sites are bone, cervical lymph nodes and bone marrow. A complete work-up at initial diagnosis is recommended to screen early metastases. Literature review showed that histopathologic grading might help to identify groups at risk.

Background Phyllodes tumors (PTs) of the breast are rare, and their prognosis and treatment are still subject of discussion. The purpose of this study is to clarify therapeutic aspects and prognostic factors of this disease. Patients and Methods We retrospectively reviewed the medical records of 106 patients who had histologically confirmed PTs collected over a period of 10 years. Results The mean age was 39.5 years (14–71 years). The mean tumoral size was 83 mm (15–250). According to criteria of Azzopardi and Salvadori, tumors were classified into 3 groups: benign (62 cases, 58.4%), borderline (16 cases, 15%), and malignant (28 cases, 26.4%). Eighty-two patients (77.4%) were treated conservatively (62 benign, 11 borderline, and 9 malignant) and 24 (22.6%) by radical surgery (5 borderline and 19 malignant). For malignant PTs treated by enucleation or local excision with or without reexcision of the tumor bed, the 5-year overall and disease-free survivals were 28.5% and 15.6% versus 72.7% and 73.6% when the surgery was radical (mastectomy with or without axillary dissection) ( P = .12 and P = .0022). For the other histotypes, this difference disappeared. The rate of recurrence was 12.2% (13) after a mean follow-up of 39 months (5 benign, 2 borderline, and 5 malignant). The treatment of recurrences consisted of radical mastectomy (8 cases), simple mastectomy (2 cases), and local excision in 3 cases. Eight patients developed metastases, 2 of whom after recurrences. The 5-year overall and disease-free survivals were 86.54% and 78%, respectively. In univariate analysis, age and recurrences are not of prognostic value for survival, whereas tumor size, histotype, necrosis, cytonuclear atypia, tumor margins, and number of mitosis were significant prognostic factors for survival. In a multivariate study, only cytonuclear atypia remained an independent predictor for survival. Conclusion According to our results, we recommend for malignant PT a simple mastectomy, whereas for borderline and benign PT, treatment is based rather on wide excision passing in healthy tissue.