Exocrine Pancreatic carcinoma in Tunisia: a retrospective study about 158 cases

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, clinico-pathological 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 was < 2 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

Genomic classification of lung cancer: toward a personalized treatment

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 year [2014] its tenth anniversary. Many other targets have been identified. The most famous and useful of them is the fusion gene ALK-EML4 but other oncogenic pathways have been implicated and are under investigations including HER2, BRAF, MET, RET…. The most relevant challenges encountered are represented by the difficulty to achieve a consensual decisional and therapeutic algorithm, the absence of standardized diagnostic techniques and the 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

Glioblastoma in Tunisia: a retrospective study about 41 cases

Background: 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.

Methods: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

Results: Median age was 54 years [13 to 72 years] and sex-ratio was 2.3. Karnofsky performance status [KPS] was <70% 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

Conclusion: 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 data

[Carcinogenesis of non small cell lung cancer and therapeutic implications]

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

[ new classification of lung adenocarcinomas according to the American Thoracic society and the European respiratory society: new recommendations to improve management]

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

[Aromatases inhibitors for breast cancer in menopausal patients]

To analyze the literature 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 literature review 30 publications concerned the topic of AI 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 significant 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

[Phenotypic and molecular changes of hemoglobinopathies in cancer]

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 h‚moglobinopathies-cancers. Our study was realized to the Institute Salah azaiz [ISA] concerning h‚moglobinopathies 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 á thalassemia. The sickle cell line represents the most wide-spread h‚moglobinopathie [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 á 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

[Medical treatment of 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

[Impact of tobacco on bronchopulmonary affections: magnitude of the problem]

Tobacco smoking is frequent in the world affecting 20 a 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 literature. In 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

[Importance of determination of protein C reactive [CRP], carcinoembryon ic antigen [CEA] and lactic deshydrogenase [LDH] in colorectal cancer]

Evaluate and show the importance of CRP, ACE and LDH in colorectal cancer. Our prospective study interested 30 patients, from 26 to 93 years old and present a colorectal cancer, confirmed histologically, during the period going from March 2003 to April 2004, and 30 healthy controls. A blood sample was collected from each patient respectively in preoperative, 48 hours before any treatment, and 6 months after surgical operation to measure serum LDH, CRP, and ACE. The mean serum of LDH, CRP and ACE values were significant higher in patients than those in controls [p respectively: 0,01; 0,04 et 0,01]. Moreover, the level of three parameters varied significantly with stages of tumor. After follow up, we have noticed e normalisation of the mean of the level of LDH, CRP and ACE with favorable evolution. Analysis of survival at 2 years showers that survival is better in patients with normal value of CRP, ACE and LDH. CRP, LDH and ACE values have a great importance during follows up after colorectal cancer surgery

[Seric soluble interleukin-2 receptor alpha in nasopharyngeal carcinoma in Tunisia. Prospective study about 45 cases]

Soluble interleukin-2 receptor alpha [sIL-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 [p < 0.0001]. 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

[Epitheloid leiomyosarcoma of the uterine cervix. About two cases]

The epithelioid Ieiomyosarcoma 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 Institut Salah AzaIz. Two patients, aged 51 and 42 years, were referred to our institution for vaginal bleeding. Tumors were classified stage II proximal and H distal [FIGO classification modified by Gustave Roussy Institute].The patients had total hysterectomy with pelvic lymph node dissection. Histological exams confirmed the diagnosis of epitheloid leiomyosarcoma of the uterine cervix. Adjuvant external radiotherapy was performed. At 12 and 36 months, the patients are alive with no evidence disease

Primary carcinoid tumours of the ovary. about three cases

Carcinoides 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

Breast carcinoma arising within fibroadenomas. Report of four observations

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%

Aim: 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

Observations: 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

Conclusion: Every benign mammary nodule must necessarily be verified surgically to avoid misdiagnosing any carcinomatous area because at this stage its prognosis is better

[Gastrointestinal stromal tumor: epidemiology and outcome study in 40 cases]

The aim of this study was to analyze epidemiology and outcome of 40 patients with gastrointestinal stromal tumor [GIST] expressed CD117. 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 benign 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 [p>0.05]. Our experience confirms that GIST is an aggressive tumor. 33.33% of them are malignant with recurrence or metastatic potential. Additionally, epidemiologic factors [age, sex and location] do not have a predictive value

[Biological investigation of thyroid cancer]

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

[Juvenile granulosa cell tumor of the ovary: a case report]

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 outcome. 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 development

[Topical and systemic chemotherapy with 5- fluorouracil in facial carcinoma secondary to xeroderma pigmentosum]

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 340mg/m 2 5-FU and preceded by an infusion of 20mg/m 2 of folic acid, day I to 5]; or C-FU protocol, combining continuous infusion of 5-FU [Ig/m 2] 5 days associated with cisplatin [100mg/m 2,dayl] 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