Lotfi Kochbati

Breast cancer in Tunisia in 2004 : a comparative clinical and epidemiological study

The aim of this study was to determine the epidemiological, clinical and anatomopathological aspects of breast cancer in Tunisia. We censored and analyzed all cases of breast cancer newly diagnosed in Tunisia during the year 2004. During that year, 1437 new cases of invasive breast cancer were diagnosed and 35 cases of non invasive breast cancer. There were 1408 women and 29 men. The accrual incidence was 27.1 and the standardized incidence was 28.5. The mean age for women was 51 years. The mean tumour size was 40.8 mm (32.3 mm and 42.5 mm for private and public sectors respectively). Tumour stage was T1 in 12.2% cases, T2 in 46.9% cases, T3 in 11.2% cases and T4 in 24.7% cases. Invasive ductal carcinoma was the most frequent (86,6%) with SBR II grade representing 54.5%. 27.7% of the patients had undergone conservative treatment. There was an unexpected increase of the incidence since 1994 where the standardized incidence was 16.9. We have noticed a moderate decrease of the tumour size of 8 mm during the last decade. This national epidemiological study on breast cancer showed an increase in the incidence of this cancer with a moderate decrease in the clinical tumour size. The relative young mean age of our patients may be explained by the age distribution in our population or by risk factors that may be particular to our country.

HPV-16 E2 physical status and molecular evolution in vivo in cervical carcinomas.

A key event in the development of cervical carcinoma is the deregulated expression of high-risk human papillomavirus (HR-HPV) oncogenes, most commonly due to HPV integration into host DNA. Here we explored whether HPV-16 E2 gene integrity is a biomarker of progressive disease with oncogenes expression. HPV-16 genome disruption was assessed by amplification of the entire E2 gene, while mRNA expression patterns of the E1, E2, E6, and E7 genes were evaluated by reverse transcription PCR (RT-PCR). As expected, E2 disruption was significantly higher among patients with cervical cancers than subjects with benign lesions (p=0.02). The status of the E2 gene correlated with tumorogenesis, and seemed also to correlate with the stage of the carcinomas, since integrated HPV-16 DNA was frequently detected in patients with advanced cancer stages (75% of stage III vs 60% stages I and II). In bivariate analysis, the lesions’ grade was most significantly associated with HPV-16 DNA disruption (p<0.05). In cervical carcinoma the deletion pattern involved more frequently the E2 gene rather than the E1 gene (62.5% vs 45.8%). The prevalence of the E6/E7 HPV-16 transcripts in cervical carcinoma specimens and in benign cervical lesions were detected with frequencies of, respectively, 91.6% and 45.4%. The mRNA levels of the HPV-16 E6/E7 genes were expressed at approximately the same levels in each physical state. We consistently observed that E6/E7 were absent or weakly detectable in the presence of E2. However, in the absence of E2 the levels of E6/E7 markedly increased (p<0.05). This study underscores the significance of investigating alternative mechanisms of E2 expression and oncogenes E6/E7 transcripts in vivo as biomarkers for disease severity in cervical carcinomas.

Correlation between ebv co-infection and HPV16 genome integrity in Tunisian cervical cancer patients

Infection with high risk Human papillomavirus (HR-HPV) is necessary but not sufficient to cause cervical carcinoma. This study explored whether multiple HR-HPV or coinfection with Epstein-Barr virus (EBV) influence the integration status of HPV16 genome. The presence and typing of HPV in a series of 125 cervical specimens were assessed by polymerase chain reaction (PCR) using the specific primers for the HPV L1 region. As for EBV infection, the viral EBNA1 gene was used for its detection through PCR amplification. Disruption of the HPV E2 gene was assessed by amplification of the entire E2 gene with single set of primers, while E2 transcripts were evaluated by a reverse transcription PCR method (RT-PCR). The overall prevalence of HPVDNA was of 81.8% in cervical cancers versus 26.9% in benign lesions. In HPV positive cases, HPV16 and HPV18 were the most prevalent types, followed by HPV types 33, 31. EBV EBNA1 prevalence was statistically more frequent in cervical carcinomas than in benign lesions (29.5%, vs 9.6%; P=0.01). No viral infection was detected in healthy control women. The uninterrupted E2 gene was correlated with the presence of E2 transcripts originating from the HPV episomal forms. It was observed that integration was more common in HPV18 and EBV coinfection. The presence of EBV caused a five-fold [OR= 5; CI= 1.15-21.8; P = 0.04] increase in the risk of HPV16 genome integration in the host genome. This study indicates that EBV infection is acting as a cofactor for induction of cervical cancer by favoring HPVDNA integration.

Place de la radiothérapie dans le traitement du rétinoblastome : à propos de 40 cas

PURPOSE The aim of this study is to analyze the results and the complications of radiotherapy in the treatment of retinoblastoma. PATIENTS AND METHODS Between 1994 and 2004, 40 children received radiotherapy for a retinoblastoma in Salah Azaiz Institute. The average age of the patients was 36 months (four to 132 months). There were 16 girls and 24 boys. Sixteen children presented a bilateral disease and 24 children a unilateral disease. Twenty eyes and thirty-six orbital cavities in 40 children with retinoblastoma were treated by radiotherapy. One child with a unilateral anterior retinoblastoma was treated with 106 ruthenium brachytherapy. External radiotherapy has been used to treat the 39 patients. In 20 cases the irradiation was conservative and in 36 cases postoperatively. The latter (n=36) presented at least one risk factor of relapses noted in the histological examination. The average dose was 44 Gy (1.8 to 2 Gy per fraction, five fractions weekly). This radiotherapy was associated with chemotherapy in 24 cases. RESULTS Thirty-five children were followed with an average follow-up of 53 months (3-108 months). The average delay of relapses was of 10 months (two to 26 months). We found four orbital relapses and seven metastasis in nine children. The conservation of the eye with a useful visual field was noted in 18 cases among the 20 conservative irradiated eyes. The major therapeutic complication was the growth defect of the bones face. A femoral bone sarcoma was noted five years after the end of the irradiation and chemotherapy in one case. CONCLUSION If the radiotherapy offers the advantage of the functional conservation and the improvement of the local control, its indications are more and more restricted in favor of the other therapeutic methods (chemotherapy, thermochemotherapy) and this considering the iatrogene risk. The development of new techniques of brachytherapy and the progresses of the conformational radiotherapy appear to reduce considerably this risk.

Larynx preservation: What is the best non-surgical strategy?

The concept of larynx preservation in locally advanced laryngeal or hypopharyngeal squamous cell carcinoma has evolved during the last three decades, especially with the advancement of nonsurgical strategies. These nonsurgical strategies include: (1) radiotherapy alone; (2) concomitant chemoradiotherapy (CCRT); and (3) induction chemotherapy followed by radiotherapy or CCRT and concurrent anti-epidermal growth factor receptor (EGFR). To date, the best approach for larynx preservation has yet to be defined. In this article, we review and discuss important recent randomized phase II/III trials investigating larynx preservation in order to facilitate the selection of an appropriate strategy in the clinical setting. However, the decision of larynx preservation should always be a multidisciplinary approach.

Situation of HPV16 E2 gene status during radiotherapy treatment of cervical carcinoma.

BACKGROUND Human papillomavirus (HPV) integration within the E2 gene has been proposed as a critical event in cervical carcinogenesis. This study concerned whether HPV16 status and E2 gene intactness are predictive of radiation response in patients with cervical cancer. MATERIALS AND METHODS Biopsies of 44 patients with cervical cancer were collected before or after radiotherapy. The presence of HPV16 was assessed by polymerase chain reaction (PCR) using specific primers for the L1 region. E2 disruption was detected by amplifying the entire E2 gene. RESULTS HPV16 DNA was found in 54.5% of the clinical samples. Overall, 62.5% of the HPV16 positive tumors had integrated viral genome and 37.5% had episomal genome. There was a tendency of increase of HPV16 E2 negative tumors compared with HPV16 L1 ones in advanced stages (75% versus 20% in stage III respectively). Detection of E2 gene appeared influenced by the radiotherapy treatment, as the percentage of samples containing an intact HPV16 E2 was more frequent in pretreated patients compared to radiotherapy treated patients (66.6% versus 20%). The radiation therapy caused an eight-fold [OR= 8; CI=1.22-52.25; p=0.03] increase in the risk of HPV16 genome disruption. The integration status is influenced by the irradiation modalities, interestingly E2 disruption being found widely after radiotherapy treatment (75%) with a total fractioned dose of 50 Gy. CONCLUSIONS This study reveals that the status of the viral DNA may be used as a marker to optimize the radiation treatment.

Cas cliniqueLymphome non hodgkinien primitif du foie : à propos d'un cas et revue de la littératurePrimary non hodgin lymphoma of the liver: case report and review of the literature

Purpose was to describe the clinical, radiological and therapeutic features in primary liver lymphoma. We report the case of a 54-year-old patient, who is followed since the age of 20 years for neutropenia associated with mediastinal adenopathy. Systematical ultrasound find a mass of the left liver confirmed by Computed tomography (CT). Histological examination of laparoscopic liver biopsy specimens confirmed diffuse large-cell non-Hodgkins lymphoma. The disease was confined to the liver without any evidence of extrahepatic involvement. The serology of Epstein Barr virus was highly positive. PET-scan show increased FDG uptake at the site of hepatic lesion and the mediastin. The patient received chemotherapy followed by radiation therapy of the left liver at the dose of 31 Gy. The patient was alive and free of disease 20 months after the diagnosis of primary liver lymphoma. The primary hepatic lymphoma is a rare malignancy, which classically affects 50-year-old patients with a male preponderance. The incidence is increased in immunosuppressed patients and some authors have suggested an association with hepatitis B or C infection, and with the Epstein Barr virus. The imaging studies including ultrasound, CT, magnetic resonance imaging (MRI) and now PET-scan help to establish the diagnosis and to the following. Treatment options are surgery, radiation, chemotherapy, or a combination.

Lymphome non hodgkinien primitif du foie : à propos d'un cas et revue de la littérature

Purpose was to describe the clinical, radiological and therapeutic features in primary liver lymphoma. We report the case of a 54-year-old patient, who is followed since the age of 20 years for neutropenia associated with mediastinal adenopathy. Systematical ultrasound find a mass of the left liver confirmed by Computed tomography (CT). Histological examination of laparoscopic liver biopsy specimens confirmed diffuse large-cell non-Hodgkins lymphoma. The disease was confined to the liver without any evidence of extrahepatic involvement. The serology of Epstein Barr virus was highly positive. PET-scan show increased FDG uptake at the site of hepatic lesion and the mediastin. The patient received chemotherapy followed by radiation therapy of the left liver at the dose of 31 Gy. The patient was alive and free of disease 20 months after the diagnosis of primary liver lymphoma. The primary hepatic lymphoma is a rare malignancy, which classically affects 50-year-old patients with a male preponderance. The incidence is increased in immunosuppressed patients and some authors have suggested an association with hepatitis B or C infection, and with the Epstein Barr virus. The imaging studies including ultrasound, CT, magnetic resonance imaging (MRI) and now PET-scan help to establish the diagnosis and to the following. Treatment options are surgery, radiation, chemotherapy, or a combination.

Cancers métachrones après traitement des carcinomes indifférenciés du cavum

Objectif Repertorier les seconds cancers observes au niveau de la tete et du cou apres traitement par chimiotherapie et/ou radiotherapie pour un carcinome indifferencie du cavum en Tunisie. Patients et methodes C’est une etude retrospective des dossiers des patients ayant developpe une tumeur secondaire (TS) apres traitement d’un carcinome indifferencie du cavum. Pour etre retenue dans cette etude, la tumeur secondaire doit etre d’histologie differente de l’UCNT initial, localisee dans le champ d’irradiation et survenant apres un delai minimum de 3 ans. Resultats Sur une serie de 2 346 patients traites de 1984 a 2001 a Tunis, Sousse et Sfax, nous avons observe 11 tumeurs secondaires, soit une frequence de 0,46 %. Les patients avaient ete traites pour des UCNT du cavum en majorite etendus T3-T4 (72 %) ou N2-N3 (63 %). L’âge median etait de 20 ans (11 a 48). Le sex-ratio etait de 0,3 (3 H/8 F). Le protocole therapeutique avait comporte une association de chimiotherapie et de radiotherapie dans 8 cas et une radiotherapie seule dans 3 cas. La chimiotherapie etait premiere dans 4 cas combinant adriamycine (40-90 mg/m2)-cisplatine (100 mg/m2) et adjuvante a la radiotherapie dans 4 cas. La dose moyenne de radiotherapie etait de 72 Gy (70 a 75). Le delai median de survenue des TS etait de 9 ans (3 a 17). Il s’agissait de carcinomes epidermoides bien differencies des VADS dans 4 cas, de fibrosarcomes cervico-mandibulaires (2 cas), osteosarcomes du massif facial (2 cas), d’un glioblastome temporal et de deux carcinomes basocellulaires du nez et de la tempe. Le traitement de la tumeur secondaire a comporte une chirurgie seule dans 4 cas et une chimiotherapie seule dans 7 cas. Aucun des patients n’a ete reirradie. La survie mediane etait de 17 mois, 4 patients sont decedes, et 7 sont vivants dont 4 en remission (24+, 36, 36 et 48+ mois) et 3 en evolution tumorale (8, 16 et 18 mois). Conclusion Les tumeurs secondaires apres traitement du cancer du cavum sont rares mais de mauvais pronosticn, justifiant leur detection et leur depistage.

Fibrosarcome secondaire de la mandibule après chimioradiothérapie pour carcinome indifférencié du nasopharynx. À 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.Resume Les cancers secondaires radio- et/ou chimio-induits ont ete rarement decrits apres traitement de cancers ORL. Nous rapportons l’observation relativement rare d’un fibrosarcome probablement radio-chimio-induit survenu sept ans apres traitement d’un carcinome epidermoide indifferencie du cavum chez un patient âge de 20 ans lors du traitement initial.