Burkitt lymphoma in a child with Bloom syndrome.

BACKGROUND: Bloom syndrome is a rare disease characterized by chromosomal instability and increased risk of developing lymphoma. OBSERVATION: We report on a case of Bloom syndrome in a 5-year-old boy with Burkitt lymphoma. The diagnosis was suspected by growth retardation, repeated respiratory infections, facial telangiectasia, and a low immunoglobulin level, then confirmed cytogenetically by sister chromatid exchanges. Chemotherapy was poorly tolerated, which required reducing the doses. Unfortunately, it was not sufficient to control the neoplasm and the patient died 14 months after diagnosis. CONCLUSIONS: Cancers in Bloom syndrome are a challenge since the potentially life-threatening side effects of the chemotherapy may require modifications in standard treatment such as dose reduction, which can compromise the tumor prognosis.

[Secondary TFE3-associated renal cell carcinoma in a child treated for Ewing sarcoma]. / Carcinome à cellules claires du rein et sarcome d'Ewing pelvien : une association rare chez l'enfant en rapport avec la translocation TFE3 Xp11.2.

Renal cell carcinoma is a rare pediatric malignant tumor of the kidney. Unlike Wilms tumor, the efficacy of chemotherapy and radiation therapy in pediatric renal cell carcinoma remains uncertain. Surgery is the best treatment and prognosis is favorable when the tumor is localized and completely eradicated. We report an exceptional observation in a 7-year-old girl with renal cell carcinoma who had been treated 20 months previously for Ewing sarcoma with chemotherapy and radiotherapy. The renal tumor was revealed by abdominal pain without hematuria. She underwent a radical nephrectomy, and histopathology concluded in renal carcinoma associated with translocation Xp 11.2 grade 3 of Furhrman pT3a N1. No adjuvant therapy was given. After 3 years of follow-up, there is no evidence of local or metastatic recurrence. This observation is significant given the very young age of this patient, the occurrence after Ewing sarcoma with a short disease-free interval. It seems that translocation renal cell carcinoma is associated with previous exposure to chemotherapy, particularly topoisomerase II inhibitors or alkylating agents.

[Lung adenocarcinoma with intramedullary spinal cord metastasis: a case report and review of the literature]. / Adénocarcinome pulmonaire avec métastases intramédullaires: à propos d'un cas et revue de la littérature.

Intramedullary spinal cord metastases are extremely rare and affect 0.1 to 0.4% of all cancer patients. We report the case of intramedullary metastases in a 42-year-old patient, 12 months after the initial diagnosis of a lung adenocarcinoma. The patient was on third-line chemotherapy for a progressive disease with node and bone metastases. He complained of weakness and difficulty walking. The MRI permitted confirmation of the diagnosis. Corticotherapy was started and the patient underwent radiotherapy. A targeted therapy was indicated. The patient died three months after the initiation of this treatment. The aim of this paper is to report a new case of intramedullary spinal cord metastases from a pulmonary adenocarcinoma, focus on its rarity and diagnostic and therapeutic difficulties through a review of the literature.

Cannabis, tobacco and domestic fumes intake are associated with nasopharyngeal carcinoma in North Africa.

BACKGROUND: The lifestyle risk factors for nasopharyngeal carcinoma (NPC) in North Africa are not known. METHODS: From 2002 to 2005, we interviewed 636 patients and 615 controls from Algeria, Morocco and Tunisia, frequency-matched by centre, age, sex, and childhood household type (urban/rural). Conditional logistic regression was used to evaluate the association of lifestyles with NPC risk, controlling for socioeconomic status and dietary risk factors. RESULTS: Cigarette smoking and snuff (tobacco powder with additives) intake were significantly associated with differentiated NPC but not with undifferentiated carcinoma (UCNT), which is the major histological type of NPC in these populations. As demonstrated by a stratified permutation test and by conditional logistic regression, marijuana smoking significantly elevated NPC risk independently of cigarette smoking, suggesting dissimilar carcinogenic mechanisms between cannabis and tobacco. Domestic cooking fumes intake by using kanoun (compact charcoal oven) during childhood increased NPC risk, whereas exposure during adulthood had less effect. Neither alcohol nor shisha (water pipe) was associated with risk. CONCLUSION: Tobacco, cannabis and domestic cooking fumes intake are risk factors for NPC in western North Africa.

[Breast cancer in Tunisia: epidemiologic characteristics and trends in incidence]. / Cancer du sein en Tunisie: caracteristiques epidemiologiques et tendance evolutive de l'incidence.

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.

[The tobacco cessation consultation of the Salah-Azeiz Tunis cancer center: one year results]. / La consultation d'aide au sevrage tabagique de l'institut de cancérologie Salah-Azeiz de Tunis : résultats à un an.

BACKGROUND: To reduce tobacco smoking is, in Tunisia, a public health priority. The tobacco cessation consultation is one of the interventions to fight against the tobacco epidemic; it is a new activity developed in the Salah-Azeiz Tunis cancer centre. The objective of this work is to evaluate the impact of the consultation on the smokers after one year of activities and to analyse the prognostic factors of tobacco cessation in order to improve the efficacy of such an activity in the future, in Tunisia. METHODS: The cessation methods were based on cognitive and behavioral therapies associated with nicotine patch, delivered free of charge. During one year (July 2003 to June 2004), 340 smokers were attended. Data on their smoking status and psychological characteristics were collected using a standardized questionnaire. RESULTS: The patients were mostly men (79%), these smokers did not present important anxiety-depressive troubles, 68% thought that they were able to quit easily. The majority (57%) smoked more than 20 cigarettes a day and was nicotine-dependent (Fagenström >7). Half of this population had already intended to stop, they declared to smoke mostly because of stress. The global cessation rate after a median follow-up of 32 weeks is 27%. The cessation rate lasting six months for 83 patients followed regularly was 23%. The good prognostic factors of cessation, after multivariate analysis, were (when taking out from the model the regular follow-up), to be confidant on the possibility to stop (OR=0.87 [0.78-0.97]). On the contrary, a high score (>7) for Fagerström test (OR=1.9 [1.1-3.4), the use of smoking to fight against stress (OR=1.08 [1.0-1.2) and a smoking environment at home (OR=4.5 [1.1-18.9]) were prognostic of a failure in quitting smoking. CONCLUSION: These results show that the cessation rate, which is still too low as compared with the literature, could be increased by a better follow-up of smokers associated with an information campaign on the existing possibilities to quit smoking in Tunisia.

Inflammatory breast cancer in Tunisia in the era of multimodality therapy.

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.

Immunolocalization of BRCA1 protein in tumor breast tissue: prescreening of BRCA1 mutation in Tunisian patients with hereditary breast cancer?

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.

Contribution of the BRCA1 and BRCA2 mutations to breast cancer in Tunisia.

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.

[Breast cancer prognosis in Salah Azaiez Institute of Cancer, Tunis]. / Pronostic du cancer du sein à l'Institut de Carcinologie Salah Azaïez de Tunis.

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.

[Breast cancer prognosis in Salah Azaiez Institute of Cancer, Tunis]

We estimated survival rate at 9 years of all [470] women with breast cancer diagnosed at Salah Aza‹ez 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

[Soft tissue epithelioid hemangioendothelioma: a case report]. / Hémangio-endothéliome épithélioïde des tissus mous. A propos d'un cas.

We report a case of epithelioid hemangioendothelioma observed in soft tissue in a 35-year-old man who presented a painful mass of the right arm which progressed in size for two years. Imaging revealed a 7-cm poorly limited expansive tumor process located in the medial muscle compartment of the right arm. Surgical resection was performed. Histological and immunohistochemical examination led to the diagnosis of soft tissue epithelioid hemangioendothelioma. The tumor recurred in the right arm and the right axillary fossa with development of multiple nodules in the contralateral thoracic wall and pleural effusion. Adjuvant chemotherapy and radiotherapy were performed, but the patient died at two years.

An open randomised trial of second-line endocrine therapy in advanced breast cancer. comparison of the aromatase inhibitors letrozole and anastrozole.

It was previously shown that letrozole (Femara) was significantly more potent than anastrozole (Arimidex) in inhibiting aromatase activity in vitro and in inhibiting total body aromatisation in patients with breast cancer. The objective of this study was to compare letrozole (2.5 mg per day) and anastrozole (1 mg per day) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with an anti-oestrogen. This randomised, multicentre and multinational open-label phase IIIb/IV study enrolled 713 patients. Treatment was for advanced breast cancer that had progressed either during anti-oestrogen therapy or within 12 months of completing that therapy. Patients had tumours that were either positive for oestrogen and/or progesterone receptors (48%) or of unknown receptor status (52%). The primary efficacy endpoint was time to progression (TTP). Secondary endpoints included objective response, duration of response, rate and duration of overall clinical benefit (responses and long-term stable disease), time to treatment failure, and overall survival, as well as general safety. There was no difference between the treatment arms in TTP; median times were the same for both treatments. Letrozole was significantly superior to anastrozole in the overall response rate (ORR) (19.1% versus 12.3%, P=0.013), including in predefined subgroups (receptor status-unknown, and soft-tissue- and viscera-dominant site of disease). There were no significant differences between the treatment arms in the rate of clinical benefit, median duration of response, duration of clinical benefit, time to treatment failure or overall survival. Both agents were well tolerated and there were no significant differences in safety. These results support previous data documenting the greater aromatase-inhibiting activity of letrozole and indicate that advanced breast cancer is more responsive to letrozole than to anastrozole as second-line endocrine therapy.

[Secondary mandibular fibrosarcoma after chemoradiotherapy for undifferentiated nasopharyngeal carcinoma. Report of a case and review of the literature]. / Fibrosarcome secondaire de la mandibule après chimioradiothérapie pour carcinome indifférencié du nasopharynx. A propos d'une observation et revue de la littérature.

Secondary tumours to radio- and/or chemotherapy have rarely been reported after treatment for head and neck cancers. We report a case of mandibular fibrosarcoma observed 7 years after chemoradiotherapy for undifferentiated nasopharyngeal carcinoma in a patient treated when 20 years old.

[Evaluation of implantable sites in medical oncology in Tunisia. Prospective study of 205 cases]. / Evaluation des sites implantables en cancérologie médicale en Tunisie. Etude prospective à propos de 205 cas.

OBJECTIVE: To evaluate the insertion and use of implantable central venous accesses in medical oncology at the Institute Salah Azaïz. METHODS: From January 1992 to June 2000, 205 patients including 179 adults (118F/61M) and 26 children aged 7 months to 72 years (mean 37 years) required the insertion of an implantable port (IP). Tumoral pathology was dominated by metastatic breast carcinoma (93/179), digestive cancer (42/179) and paediatric cancer (26 cases). RESULTS: Excluding 3 initial failures, we inserted 205 IP for 202 patients. The supraclavicular anatomic way (Yoffa) was used in 156/205 cases and the subclavicular (Aubaniac) for the resting 32 cases with a jugular conversion in 17 cases. Initial complications were represented by 6 arterial puncture (2.9%), 3 pneumothorax (1.5%) and 1 catheter migration in the right pulmonary artery. Median life duration of the material was 210 days (3 to 1460 days) for adults and 185 days (3 to 1460 ays) for children. Mean life duration for the 205 IP was 240 days +/- 239 (3 to 1460 days) with a total of 49,200 IP-days. We explanted 17 IP for infection (8 cases), cutaneous ulceration (8 cases) and actinomycin extravasation (1 case). We observed 6 cases (2.9%) of subclavian and jugular thrombosis treated by anticoagulants and conservation management of the port. Presently, 58 patients are alive with IP in place. CONCLUSION: Implantable ports represent a useful option in medical oncology for patients treated with prolonged chemotherapy and adjuvant treatments such as antibiotics, transfusion. This method allows a good comfort for the patients and also the treating team but requires a prealable training for the nursing team.

Frequency and genome load of Epstein-Barr virus in 509 breast cancers from different geographical areas.

Since the few data exploring a possible association between Epstein-Barr virus (EBV) and breast cancer are conflicting, we investigated this association together with the influences of geographical areas. 509 breast cancers were sampled from areas with varying risks of nasopharynx carcinoma (NPC) such as North Africa (Algeria and Tunisia, high-risk area); southern France (Marseille, intermediate-risk area); and northern Europe (northern France, the Netherlands and Denmark; low-risk areas). Polymerase chain reaction (PCR) of a subregion of EBV BamHIC encoding the EBERs demonstrated that 31.8% of the tumours contained the viral genome. No significant differences were observed among the geographical areas. However, positive samples showed higher loads of the EBV genome in the NPC high- and intermediate-risk areas than in the low-risk areas. EBV type 1 was the dominant strain. In situ hybridization studies using a(35)S-labelled riboprobe for EBER1 and a laser capture microdissection, combined with quantitative PCR, showed that EBV localization was restricted to some tumour epithelial cell clusters. EBV could not be detected in the stroma. Considering the whole population covered, the presence of the EBV genome was not correlated with age, menopausal status, tumour, size, nodal status or histological grade.

[Dispensation of opioids by pharmacists in Tunisia]. / Dispensation des opioïdes par les pharmaciens en Tunisie.

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.

[The use of neuron specific enolase in the prognosis and followup of neuroblastoma in children. Results of a retrospective series of 21 patients]. / Apport de la neuron specific enolase dans le pronostic et le suivi des neuroblastomes de l'enfant. Résultats sur une série rétrospective de 21 patients.

OBJECTIVE: To report the results of seric neuron specific enolase in pediatric neuroblastoma. PATIENTS AND METHODS: Our retrospective study concerns 21 children treated in our institution from 1992 to 1998 for neuroblastoma. Seric NSE was determined by immunoenzymology technique at different stages of the disease and the treatment. RESULTS: Mean value for the 39 dosages of the whole patients was 127.9 ng/ml with a sensitivity of 56%, five patients has presented normal values. Mean value for the 18 patients in stage IV was 132.38 ng/ml. We also observed in 3 patients, an evolution of the seric NSE parallel to this of the disease under chemotherapy. CONCLUSION: NSE represents a moderate sensitive and specific tumor marker for pediatric neuroblastoma. However, it represents a good value in prognosis and follow-up after chemotherapy.

[Dermatomyositis and nasopharyngeal carcinoma: 3 cases]. / Dermatomyosite et cancer du cavum : 3 observations.

BACKGROUND: Nasopharyngeal carcinoma is a common cancer in Tunisia with an estimated incidence of 1.8/100,000. The tumor shows a characteristic association with paraneoplastic syndromes. CASE REPORTS: We report three cases of histologically proven dermatomyositis associated with nasopharyngeal carcinoma in patients aged 40, 24 and 65 years. In all cases, the course of the paraneoplastic syndrome ran parallel to the nasopharyngeal carcinoma. DISCUSSION: Dermatomyositis is one of the numerous paraneoplastic syndromes associated with nasopharyngeal carcinoma. Systematic examination of the nasopharynx is required in case of dermatomyositis.