Primary bone lymphoma: tunisian multicentric retrospective study about 32 cases.

AIM: To report the epidemiologic, clinical features, treatment modalities and prognosis of primary bone lymphomas (PBL) within a retrospective Tunisian series. METHODS: We collected cases of histologically confirmed PBL in 3 medical oncology departments from northern and central Tunisia andwe analyzed their characteristics. RESULTS: From January 1990 to July 2014, we collected 32 patients with histologically proven PBL, having a median age of 53 years. They affected mainly the long bones and diagnosed at early stages. 91% of the PBL were large cell B lymphoma. All patients received CHOP or CHOP-likeChemotherapy (CT), associated to Rituximab in the last 9 cases, with 14/32 patients received loco-regional radiotherapy and one patient had a resection-reconstruction surgery. We observed 90% of objective responses after primary CT.With a median follow-up of 38.5 months (1 to 192), the 5-year overall survival OS rate was 63%.18 patients relapsed and 14 remain alive in complete remission. CONCLUSION: PBL remains a rare disease lately diagnosed in Tunisia. However, most of the patients had early stages tumors. Furthermore, the efficacy of CT and introduction of Rituximab leads to a high rate of complete/objective responses, improving the survival rate.

Overexpression of FOXM1 Is a Potential Prognostic Marker in Male Breast Cancer.

BACKGROUND: Several studies have outlined biological differences between female and male breast cancer (MBC) and concluded that MBC should be considered as an entirely separate disease. Whether FOXM1 has any indication for prognosis in MBC patients remains unknown. We sought to examine the expression levels of FOXM1 in MBC and to identify the relationship between FOXM1 expression and patient survival. PATIENTS AND METHODS: FOXM1 expression was evaluated in a total of 130 MBC specimens. RESULTS: FOXM1 was overexpressed in 37% of the MBC samples. FOXM1 overexpression was significantly associated with tumor size (p = 0.045), histological grade (p = 0.048), lymph node metastasis (p = 0.012), Ki-67 proliferation index (p = 0.016), and molecular subtypes (p < 0.001). Multivariate analyses indicated that FOXM1 was an independent prognostic factor for overall survival in MBC patients (p < 0.001, hazard ratio = 0.69 (0.43-0.96)). CONCLUSIONS: Overexpression of FOXM1 was associated with well-established markers of poor prognosis; thus FOXM1 may represent a potential novel prognostic marker for MBC.

[Metastatic non-small cell lung cancer: a Tunisian retrospective study about 100 cases]. / Cancers Broncho-pulmonaires non à petites cellules métastatiques : Etude tunisienne retrospective à propos de 100 cas.

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

Ki-67: role in diagnosis, prognosis and follow-up after treatment of breast cancers.

AIM: To evaluate the literature data about diagnostic value, prognosis value and interest in follow-up of Ki-67 antibody after treatment for breast cancer. METHODS: We performed a literature search in pubmed using the keywords : Ki-67, anti-Ki-67, breast cancer, prognosis, proliferation, chemotherapy, hormone therapy. RESULTS: Ki-67 is routinely used as a static marker of proliferative activity and in follow-up-monitoring before and after treatment by chemotherapy and more recently hormonotherapy. Ki-67 was also used at a cut-off of 14% to differentiate between luminal A and B breast cancers. A high Ki-67 expression is probably related to a poorer prognosis but also a better response to neoadjuvant chemo and/or targeted therapy. More recently, genomic analysis is more reliable to classify the molecular breast cancer subtypes avoiding the possible cases of discordant Ki-67 rate. Ki-67 is also interesting in predicting histological response to neoadjuvant chemo and hormone therapy. CONCLUSION: Ki-67 evaluated by immunohistochemistry is important in routine in countries without bimolecular plateforms despite technical insufficiencies. When available, genomic grading is better to classify molecular subtypes and determine breast cancer prognosis in adjuvant and neoadjuvant setting.

Breast cancer in Tunisia: association of body mass index with histopathological aspects of tumors.

BACKGROUND: Previous studies have suggested a link between obesity and breast cancer (BC). However, there is no universal consensus, especially in population based studies. Because only few studies have been conducted on African women, we aimed here to assess the relationship between BMI at time of diagnosis and the BC histopathological features among Tunisian patients according to menopausal status using a hospital-based prospective cohort study. MATERIALS AND METHODS: Clinical and pathological data were collected from 262 patients stratified on four groups according to their BMI. The relationship between BMI and histopathological features at diagnosis was analysed using univariate and multivariate analysis. Receiver-operating characteristic (ROC) curves were used to evaluate the performance of BMI in predicting of high tumor grade, in comparison to ki-67 index of proliferation. RESULTS: Obesity was correlated with larger tumors, advanced grade and with ER-PR- Her2+ BC subtype. An association of BMI with tumor size and tumor grade was observed in both premenopausal and postmenopausal women. Additionally, a significant association between BMI and ER+, ER+PR+Her2+ and ER-PR-Her2+ status was revealed for premenopausal patients, while only ER+PR+Her2+ was associated with BMI for postmenopausal women. Finally, our results showed that compared to Ki67 proliferation index, BMI is a useful prognostic marker of high grade BC tumors. CONCLUSIONS: These data are the first to show that in Tunisia obese women suffering from BC have significantly larger tumors and advanced tumor grade and that higher BMI might influence tumor characteristics and behavior.

Breast cancer in Arab populations: molecular characteristics and disease management implications.

Breast cancer is a major health problem in both developing and developed countries. It is the most frequently diagnosed female malignant disease in Arab populations. The incidence of breast cancer is lower in Arab countries than in Europe and the USA but is rising fast. Breast cancers in women from Arab populations have different characteristics to those reported in individuals from Europe and the USA. For example, affected patients are at least a decade younger, they have a more advanced stage of disease at first presentation, and their tumour size is larger. Moreover, in some Arab populations, reports suggest increased axillary-lymph-node invasion, a larger proportion of negative hormone receptors, and a higher tumour grade. These disparities are not only confined to clinicopathological features but also exist at the molecular level, as shown by findings of genome-wide association studies and expression profiling.

Testicular cancer patterns in Tunisian men : diagnosis problems, pathological types and prognosis. About 41 patients.

AIM: To analyze the testicular cancer (TCa) incidence, diagnosis aspects, pathologic grade, stage, and survival in Tunisian men. METHODS: We studied all patients who had histopathologically confirmed TCa treated in La Rabta University-Hospital between 1991 and 2010. Baseline demographic data included age at diagnosis, year of diagnosis, clinical symptoms, stage at diagnosis, histologic type, management strategies and survival were analyzed. RESULTS: The incidence of TCa among Tunisians is very low; we collected only 41 cases over a period of 20 years with an average incidence of 2 new cases per year. Peak age incidence was 30-49 years. Testicular swelling was the principal complaint in 25 patients. 58.5% of tumours were rightsided and 39% were left-sided. There was bilateral involvement in only one case. The mean interval between onset of symptoms and presentation was 16.5 months (1-120). Most patients presented at stages T2 and T3 (63.4% and 26.8% respectively). Treatment consisted of radical orchidectomy in all patients and cisplatin-based chemotherapy and radiotherapy in respectively 11 and 12 patients (association in 5 patients). One patient with a tumour in an intra-abdominal testis underwent laparotomy. The most common histological types were seminomas (n=20) and mixed germ cell (n=8). Three patients died within 48 months, while half were lost to follow-up. CONCLUSIONS: The incidence of TCas in Tunisia remains low. Late presentation and treatment are major challenges to management. Better health funding and education regarding testicular self examination is essential.

Prognostic value of preoperative carcinoembryonic antigen level in colorectal cancer in Tunisia.

AIM: To evaluate the prognostic value of preoperative serum carcino-embryonic antigen (CEA) level in patients with colorectal cancer. METHODS: This retrospective study included 125 colorectal cancer patients aged from 14 to 87 years, surgically treated between January 2001 and December 2006. Preoperative serum CEA was measured by chemiluminescence assay. RESULTS: within the patients, 57 were males and 68 females. They have tumours classified Dukes A in 2 patients, B in 24 patients, C in 53 patients and Dukes D in 46 patients. Median follow-up period was 24 months (range, 4 - 72 months). The relapse-free survival was significantly higher in patients with CEA < 5 ng/ml compared to CEA ³ 5 ng/ml, (p < 0.0001). We observed significant differences in relapse-free survival between patients with CEA < 5 ng/ml and those with CEA ³ 5 ng/ml among patients classified as Dukes stage B (p=0.007) and C (p < 0.0001). However, there was no significant difference in relapse-free survival among those classified as Dukes stage D. Cox multivariate analysis demonstrated that preoperative serum CEA level was a significant independent prognostic factor for relapse-free survival (hazard ratio: 6.49, 95% CI, 3.09 to 13.62, p < 0.0001). CONCLUSION: Preoperative serum CEA is a reliable predictor factor for recurrence in patients with CRC. CEA might be used in staging system and will be useful for therapeutic orientation in patients undergoing curative resection of CRC.

Genetic homogeneity of mutational spectrum of group-A xeroderma pigmentosum in Tunisian patients.

BACKGROUND: Xeroderma Pigmentosum (XP) is a rare autosomal recessive disorder characterized by cutaneous and ocular alterations. Eight genes, Xeroderma Pigmentosum group A (XPA) to Xeroderma Pigmentosum group G (XPG) and Xeroderma Pigmentosum group V (XPV), are known to be responsible for the disease and products of these genes are involved in the repair of deoxyribonucleic acid (DNA) lesions generated by UV radiation. Several XP patients suffer from neurological defects, found in the XPA (the most common form), D and G groups. The aim of this study was to investigate the mutational spectrum of XPA in Tunisia, in order to propose a simple tool for molecular diagnosis. METHODS: This study was carried out on six unrelated families with nine Tunisian XPA patients. Clinical features were recorded. As a previous study showed the presence of the R228X mutation in Tunisia, patients were first screened for this mutation by polymerase chain reaction-restriction fragment length polymorphism and then confirmed by direct sequencing. RESULTS: The results showed that all patients carried the XPA R228X mutation. This mutation corresponds to a C to T transition, which creates a premature stop codon at position 228, thus causing a DNA repair defect. CONCLUSIONS: The XPA R228X mutation is common in Tunisian population. This mutation is associated with a relatively moderate phenotype of the XPA. As all explored patients presented the recurrent mutation XPA R228X, a potential founder effect was searched and confirmed by haplotype analysis. Taking into account similar genetic background, investigation of this mutation should allow a cost effective and rapid diagnosis of XPA in north-African populations.

[Conserving surgery for breast cancer]. / Le Traitement Conservateur du Cancer du Sein.

Breast cancer is the first women's cancer. Conserving surgery associated with radiotherapy, is in progress. Her indications are frequent. The result for local control and global survival are the same as radical surgery.

Expression of WISP3 and RhoC genes at mRNA and protein levels in inflammatory and noninflammatory breast cancer in Tunisian patients.

Previous studies have shown the expression WISP3 and RhoC in cell lines of inflammatory breast cancer (IBC). The aim in the current study was to compare the expression of both genes, in biopsy samples collected from Tunisian patients with localized or metastatic breast cancer and patients with IBC. We investigated 127 patients enrolled in Salah Azaiez Institute in Tunis. Using the RT-PCR, we showed the phenotype (WISP3-, RhoC+) is significantly associated with IBC tumors, while the (WISP3+, RhoC-)phenotype is mostly associated to non-IBC tumors. The frequencies of these tumor phenotypes are significantly different between these tumor groups (p = 10(- 7); relative risk or RR = 3.25; confidential interval or CI 95% = 1.90-5.53). Immunohistochemical test revealing the presence of WISP3 and RhoC proteins correlates with the expression in the biopsy of their encoding genes as detected by RT-PCR. In conclusion, it appears that WISP3 and RhoC genes expression status defines a molecular signature of IBC.

Gestational trophoblastic disease in Tunisia.

OBJECTIVE: The aim of our study is to evaluate the frequency of the gestational trophoblastic disease (GTD) in Tunisia, and describe its risk factors and clinical presentations. We also precise therapeutic features used in our country and compare them to those proposed in the literature and finally suggest concrete recommendations. METHODS: We studied retrospectively the cases of GTD proved histologically, occurring during the three years (2000-2001-2002) in the departments of genecology obstetrics of Tunisia and the department of medical oncology of the Salah Azaiz Cancer Institute. RESULTS: The frequency of the GTD in Tunisia is 1 per 918 deliveries. The frequency of the CHM (complete hydatiform mole) is estimated to 68.15% of all the cases of GTD and 1 per 1347 deliveries whereas the frequency of the PHM (partial) is estimated to 30.57% and 1 per 3004 deliveries. The mean gestational age at the moment of the diagnosis is of 11.5 week of amenorrhea (WA) for CHM and 11 WA for the PHM. The metrorrhagia is present in 75% of the CHM and 67% of the PHM. Ultrasonography showed a typical snowstorm aspect in 55%. The mean rate of HCG is 162 x 10(3) UI/l. Vacuum aspiration was performed in all the CHM and in 89.5% of the PHM. One patient followed up for PHM was treated by hysterectomy. 21% of the cases were complicated by trophoblastic retention. Two patients were treated by initial chemotherapy for invasive mole and metastatic mole. 84% of the patients reached complete healing. After treatment of the molar pregnancy, two patients (1.27%) recurred. CONCLUSION: Our results suggest some recommendations: In our practice, all abortion products must be addressed to histopathological examination. The patients must be surveyed during at least one year to detect the occurrence of a GTN. The classification and treatment of the GTN must be codified Modem therapy for gestational trophoblastic diseases (GTDs) has resulted in high cure rates while preserving fertility.