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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.

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.

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.

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.

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.

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.

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.

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.

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

Breast myoepithelioma is rare. A case is reported of a 71 year old female. The tumor was clinically, radiologically and macroscopically demarcated. Diagnosis was based on histological and immunohistochemical studies. At the time of diagnosis the tumor was composed of myoepithelial cells with few cellular atypias and a low mitotic activity. Tumor cells expressed vimentin, actin, S100 protein and cytokeratin. No local or distant metastases were found. The patient had been treated initially with a large excision of tumor. Local recurrences detected 1 year after initial surgery and showed a similar morphology and immunoreactivity with higher mitotic activity. Mastectomy with axillary dissection was performed. No recurrences and no distant metastases detected 2 years later. Myoepithelial tumors generally considered as benign or low-grade lesion can give rise to a wide range of clinical evolution.

Cyfra 21-1 is a recognised marker for epidermoid lung and head and neck carcinomas oriented to the cytokeratin 19 that is expressed particularly in malignant epithelial cells. The aims of this study were to evaluate the importance of the use of this marker in nasopharyngeal carcinoma (NPC). Our prospective study interested 41 patients (33M/8F) with a mean age of 44 years (13 to 70) with 8 of them aged less than 30 years, presenting a nasopharyngeal carcinoma histologically confirmed from September 1999 to March 2000 and 45 healthy controls without evidence neoplasm. Undifferentiated forms represent 90.2% of cases and lesions are staged T2, T3 and T4 in 2.4%, 36.6% and 61% of cases, while N1, N2 and N3 represent 9.8%, 26.8% and 41.5% of cases. A blood sample was collected from each patient and control before any treatment, as well as controls to measure Cyfra 21-1 by immunoenzymatic assay, 2 groups of patients were selected after a period varying from 4 to 37 months with a median of 29 months: 27 patients with favourable evolution (without evidence of disease after initial treatment), 12 patients with non favourable evolution (1 death, 2 cases of loco-regional relapse and 9 patients with metastatic disease). 2 patients were lost to follow-up. The results showed that the mean serum Cyfra 21-1 values were significantly higher in patients with NPC than those in controls (p = 0.001). A significant correlation was found between the serum Cyfra 21-1 level before treatment and the clinical outcome of patients (p = 0.0009). Patients having a favourable evolution have the lowest level. Seric level of Cyfra 21-1 at diagnosis of NPC may play a predictive role to evaluate the risk of metastatic disease and prognosis.

Data from the files of 12 patients with pur ovarian dysgerminoma managed between January 1970 and december 1990 were evaluated. Pur ovarian dysgerminoma accounts for 2% of all ovarian malignancies and 28% of malignant germ cell tumors. A palpable pelvic mass was detected in three-fourth of patients. Echography objective ovarian tumor in all cases. Diagnosis was histological. Primary treatment was surgery followed by radiotherapy in 8 cases and chemotherapy in 2 cases. 2 patients developed local recurrences were irradiated and 1 patient developed distant metastases was given chemotherapy in association to radiotherapy. The 5 years survival rate was 91.7%.Treatment of ovarian dysgerminoma remains controversial. However, patients with stage la who desire further childbearing can be safely treated with unilateral adnexectomy. For all other patients, radical surgery followed by radiation therapy or chemotherapy for the advanced stages and recurrents dysgerminoma is the treatment of choice. Prospective randomized clinical trials are needed for a well codified therapeutic strategy.

The authors report the result of a retrospective study of 7 cases of struma ovarii, four malignant and three benign cases, removed surgically at the Salah Azaiez Institute, Tunis, Tunisia, over a period of 20 years (1980-2000). Based on their personal experience and on a review of the literature, the authors discuss the diagnosis, management and outcome of struma ovarii, in particular with malignant transformation. Echography objectives pelvic tumor in all cases. The diagnosis is usually histological. Treatment is exclusively surgically, all patients with malignant struma ovarii were staged la (FIGO). Mean follow up was 4 years and 4 months (range: 1-7 years). No recurrences were reported and no distant metastases. Supervision was based on serum level thyroglobuline and scintigraphy with iodine 131. Histologic diagnosis of malignancy is difficult. Treatment is based on surgery and prognosis is relatively favorable even in malignant cases.

Rectal cancer is a different entity compared to colon cancer due to its particular clinical therapeutic and treatment failure profile. Its anatomical situation explain the more higher frequency of loco-regional relapses compared to its colic counterpart. Adjuvant therapy of rectal cancer follow the progress obtained in colon cancer using adjuvant fluorouracil based chemotherapy and is also based on radiotherapy. This treatment is frequently used as primary to reduce tumoral volume, to improve the quality of surgery and to decrease the risk of local relapses. Doses fo 20-30 Gy seems to be the standard for bulky lesions and.

Our objective is to compare clinical and biological presentation of patients with bone metastatic disease.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).Even conventional, some biochemical markers as ALP and LDH remain useful in the diagnosis and prognosis in patients with proven bone metastasis.

The sarcoma of the penis is a very rare tumor more exceptional is the Leiomyosarcoma of the penis for which the diagnosis required an immunohistochemical study. The prognosis for this tumor is poor. We report a case, which arise to a 53 year-old-man in this instance we did a review of the medical literature.