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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. [ABSTRACT FROM AUTHOR]

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.)

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.

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.

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.

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.)

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.

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.

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.

Between 1981 and 1985, the authors studied 21 Tunisian patients with alpha chain disease. Twenty of 21 underwent laparotomy. According to Galian et al. six patients were classified Stage A, two Stage B, and 13 Stage C. The therapeutic regimen included the following: (1) Antibiotics: In the case of intestinal bacterial overgrowth (IBO), antibiotics selected by their antibiograms were delivered; in absence of IBO, metronidazole plus ampicillin were first given. The antibiotic treatment was changed in case of therapeutic failure. (2) Chemotherapy: From 1981 to 1983 a cyclophosphamide, Adriamycin (doxorubicin), teniposide (VM-26), prednisone (CHVP) protocol (Adriamycin 35 mg/m2, teniposide 50 mg/m2 day 2, cyclophosphamide 300 mg/m2 days 2 through 4, prednisone 40 mg/m2 days 1 through 10) was used. After 1983 bleomycin 15 mg, Adriamycin 30 mg, vinblastine 10 mg were given on day 15. Serum immunoelectrophoresis and immunohistochemical study of duodenojejunal specimens were made on a 3-month and 6-month basis, respectively. Survival curve analysis was made according to Kaplan and Meier. Results were as follows: (1) Stage A: Six patients were first treated by antibiotics alone; two complete responses (CR) persisting 42 and 55 months later were observed, respectively. The four antibiotic failures were submitted to further chemotherapy with four subsequent failures and two deaths. (2) Stage B-C: Chemotherapy led to nine CR with one precocious relapse, a salvage chemotherapy allowing to one more CR. (3) All stages mixed, percentage of survival reached 90 +/- 12% at 2 years and 67 +/- 25% at 3 years, all patients alive beyond 3.5 years being disease-free.

Carcinoma of the cervix is still common in Tunisia, where it occupies second place among malignant diseases in women. Accounting for 17% of the female population of the National Cancer Institute of Tunis, it is preceded only by breast cancer (27%). Study of the factors concurrent with the origin of carcinoma of the uterine cervix seems to indicate that its decrease is secondary to the lowered average age at marriage, to the fall in the reproduction rate among the population at large, and to improved socio-economic conditions among the poorer classes. Study of clinical features observed during two separate periods of 10 years shows a modification in the physiognomy of this cancer, with, notably, a larger frequence of lower stages (45% of stage II in 1984 vs 20% in 1974) and a slight tendancy towards the discovery of smaller non - or early - infiltrating tumors (4% in 1984 vs 0% in 1974). Efforts must continue to be made in the domaine of early detection, especially among the "high risk" population.