The CC-genotype of the cyclooxygenase-2 gene associates with decreased risk of nasopharyngeal carcinoma in a Tunisian population.

BACKGROUND: The cyclooxygenase-2 (cox-2) pathway is now recognized to be important in human cancer development and progression. The gene for cox-2 carries a common single nucleotide polymorphism, T8473C, located within a potential functional region in the 3'-UTR of cox-2 gene was identified. We have investigated the frequencies of cox-2 genotypes in Tunisian population to determine whether that polymorphism was associated with the risk of nasopharyngeal carcinoma (NPC) in Tunisian population. MATERIAL AND METHODS: One hundred and eighty-nine NPC patients were compared to 237 healthy controls. RESULTS: The cox-2 T8473C polymorphism was significantly associated with NPC (P=0.031). The CC-genotype and C allele were more frequent in control compared to patients group [CC: OR=0.37; P=0.013; 95% CI: 0.17-0.81; C: OR=0.72; P=0.032; 95% CI: 0.53-0.97]. Multivariate logistic regression analyses revealed that the CC-genotype was associated with a significantly decreased risk of NPC (P=0.013). Tumor sizes, histologic grade, presence of primary lymph node metastases, age or sex were not associated with cox-2 genotypes. CONCLUSION: We conclude that the CC-genotype and C allele of cox-2 T8473C gene polymorphism are associated with decreased risk of nasopharyngeal carcinoma in a Tunisian population.

[Thyroid carcinoma and Hashimoto thyroiditis]. / Carcinome de la thyroïde et thyroïdite de Hashimoto.

OBJECTIVES: To study of the association between thyroid carcinoma and Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: [corrected] Retrospective study of 78 patients undergoing surgery between 2001 and 2002, with a pathological diagnosis of Hashimoto's thyroiditis. The clinical data and complementary tests performed before surgery are reported. RESULTS: The mean age was 44.6 years, with 77 females and only one male. There were 12 cases of thyroid cancer associated with HT, mostly with the nodular form, with 11 papillary carcinoma (14.1%) and one non-hodgkin B lymphoma of the thyroid. Tumor size varied from 4 to 60 mm with a mean of 26 mm. There was one microcancer (size<10 mm). CONCLUSIONS: We did not find an increased incidence of thyroid cancer associated with this highly selected population of HT patients.

[Epidemiology of nasal and paranasal sinus cancer in Tunisia]. / Epidémiologie des cancers du massif facial en Tunisie.

OBJECTIVE: To report the epidemiological and clinical features of nasal and paranasal sinus cancers collected during a period of 35 years at the Salah Azaiez Institute of Tunis. MATERIAL AND METHODS: This retrospective study concerned patients with histologically confirmed nasal and paranasal sinus cancers treated at our institute from 1969 to 2004. We collected the following data: age, sex, residence (rural or urban), site, occupation and professional exposure, histological type and tumor extension. RESULTS: We identified 265 cases (163 M; 102 F; Sex-ratio=1.65) with a mean age of 60 years (3 months - 91 years). Epidermoid carcinoma (47%) and adenocarcinoma (16%) predominated followed by sarcoma (14%) and melanoma (6%). We observed only 2 cases (0.7%) of ethmoidal adenocarcinoma. CONCLUSION: Nasal and paranasal cancers in Tunisia are linked more to chronic rhino-sinusal inflammation than professional exposition (wood).

Usefulness of IGF-1 serum levels as diagnostic marker of nasopharyngeal carcinoma.

BACKGROUND: The role of IGF-1 in promoting cancer has been investigated for many years. The aim of this study is to explore the relationship between rates of IGF-1 and NPC and to evaluate association of IGF-1 with clinical parameters. MATERIALS AND METHODS: IGF-1 levels was measured by Elisa test among 82 NPC patients and 60 healthy controls RESULTS: Our results showed, for the first time, a significant increased levels of IGF-I in NPC by in comparison with healthy controls (p<0.01). According to the age, sex and tumor size of NPC patients, we demonstrated that IGF-1 concentrations are significantly higher in NPC aged over 30 years compared to patients aged less than 30 years (p<0.01). The IGF-1 levels are, also, higher among women compared to men (p<0.01). The concentrations of IGF-1 were positively correlated with tumor size of NPC patients (p<0.01). CONCLUSION: IGF-I could be a good nasopharyngeal cancer diagnostic marker.

Association analysis of HLA-class II and class III gene polymorphisms in the susceptibility to mediterranean visceral leishmaniasis.

HLA-DRB1, -DQB1, TNFalpha, TNFbeta, HSP70-2 and HSP70-hom genetic polymorphisms were analyzed in 156 unrelated patients who developed mediterranean visceral leishmaniasis (MVL) due to Leishmania infantum, and 154 unrelated healthy controls, who have got asymptomatic infection with this parasite and were selected on the basis of a positive leishmanin skin test (LST). A significantly reduced frequency of HLA-DR2 was observed among MVL patients (16.1%), compared with controls (26.3%) (relative risk = 0.54; p = 0.04). HLA-DR2/DR13 as well as HLA-DQB1*0201/- genotype frequencies were significantly lower in patients vs controls (relapse rate = 0.17 and 0.46, respectively; p < 0.05). However, using Bonferroni correction, none of these associations remained significant. No association was found, between either the -308 base pair TNFalpha gene polymorphism or the NcoI polymorphism in the first intron of the TNFbeta gene and susceptibility to MVL. Analysis of PstI and NcoI polymorphisms in the coding region of HSP70-2 and HSP70-hom genes, respectively, revealed a significantly higher frequency of homozygotes for the HSP70-2/PstI negative allele, among patients (21.8%) vs controls (12.6%) (relapse rate = 1.94; p = 0.04). Again, this result was not significant after using Bonferroni correction. These results do not support association between susceptibility to MVL and the MHC class II and class III loci analyzed in this study.

[Secondary head and neck osteosarcoma following treatment of undifferentiated nasopharyngeal neoplasms (UCNT)]. / Ostéosarcome secondaire de la tête et du cou après traitement de carcinome indifférencié du nasopharynx (UCNT).

Secondary tumours after radio and/or chemotherapy are mainly of hematopoietic (acute non lymphoblastic leukemia, non-Hodgkin lymphoma) or soft tissue lineage previously described most frequently after breast cancer and Hodgkin disease treatment with radio and/or chemotherapy. We report two cases of classical osteosarcoma's observed 9 and 3 years after treatment for UCNT with combined radiotherapy and alkylant-based adjuvant chemotherapy in one case and exclusive loco-regional irradiation in the second case.

[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.

[Intraoperative brachytherapy in the management of keloids. Apropos of 114 cases] . / Place de la curiethérapie dans le traitement des chéloïdes. A propos de 114 cas.

PURPOSE: Keloid scars are unsightly, especially when located on the face or bare zones. The purpose of this study was to evaluate the therapeutic results of intraoperative brachytherapy in the management of keloids. MATERIAL AND METHODS: This retrospective study was based on the study of 82 patients with keloids treated in Salah Azaiz Institute (Tunisia) between 1982 and 1994 (65 women and 17 men). The mean age of patients was 23.4 years (+/- 8.4). A total of 114 lesions have been treated with surgical resection and intraoperative brachytherapy using an iridium source placed under the surgical scar. The length of iridium was chosen with the result that the radioactive thread exceeded 5 mm on each side of the surgical scar. The iridium source was loaded less than six hours after resection. Average iridium activity was 1.5 +/- 0.3 mCi/cm. Average iridium length was 56.8 +/- 34 mm. The referred isodose chosen for the target volume included the surgical scar and a margin of 5 mm around the iridium source, which was placed under the surgical scar. The average administered dose was 20.4 Gy (+/- 3.2 Gy). RESULTS: The 2-year local control rate was 87% for the whole group of lesions treated (n = 114). Local control rate of keloids processed by resection and intraoperative brachytherapy as the first treatment (59 cases) was 96% at two years. This rate was better than the local control of lesions that had been previously treated with anterior surgical resection (84% in 55 cases). For the latter group, lesions treated with a dose of more than 20 Gy had better local control, but the difference was not statistically significant (87 vs. 65% at two years, P = 0.41). CONCLUSION: Intraoperative brachytherapy is effective for improving local control of keloids and preventing a recurrence. A rigorous technique and an adequate dose according to previous surgical treatment allows very good results.

[Primary sino-nasal lymphomas. Apropos of 25 cases]. / Lymphomes primitifs nasosinusiens. A propos de 25 cas.

PURPOSE: To report on the epidemiological and therapeutic features of a series of Tunisian patients treated for primitive sinonasal lymphoma. PATIENTS AND METHODS: Our retrospective study concerns patients with histologically proven primitive sinonasal lymphoma diagnosed and treated at our institution from 1975 to 1997. Initial work-up included: clinical plus ENT examination, WBC, ESR, LDH, abdominal ultrasonography, bone marrow biopsy and facial CT-scan taken since 1985. All slides are reviewed and reclassified using the Kiel system. Treatment is based on radiotherapy with or without chemotherapy (mainly with the CHOP protocol). RESULTS: We collected 25 patients (22 males and three females, sex-ratio = 7) with a mean age of 48 years (18 to 78). Mean delay of consultation is 4 months and patients consulted mainly for nasal obstruction (65%), more rarely epistaxis (40%) or rhinorrhea. ENT examination showed a fungating nasal fossa tumor in 20% of cases, predominantly unilateral (80%), associated to cervical nodes in 25% of cases. High-grade lymphomas represented 60% of the cases, and 60% of the patients were stage IE. All stage IEs have been treated by exclusive radiotherapy while more advanced stages received combined chemo- and radiotherapy (eight patients). The five-year actuarial survival rate was 69% for the whole population, with a better prognosis for localized stage and low-grade lymphomas. DISCUSSION: Radiotherapy remains a standard treatment for sinonasal lymphomas, permitting us to cure localized stages. In extended stages (more than IE), combined chemoradiotherapy seems to be a good option, especially in case of bulky tumors as observed for the other nodal and extra-nodal head and neck lymphomas.

[Regional failure of hypopharyngeal squamous cell carcinoma]. / Echecs ganglionnaires du carcinome épidermoïde de l'hypopharynx.

PURPOSE: Lymph nodes and distant metastases contribute to the poor prognosis of hypopharyngeal squamous cell carcinoma. The purpose of this study is to estimate the frequency, mode and prognosis factors related to regional and distant metastasis. PATIENTS AND METHOD: The authors' report is based on a retrospective study concerning 271 hypopharyngeal squamous cell carcinoma, compiled in the service of Surgery of Head and Neck Cancers of the Salah-Azaïz Institute (1977-2002). Frequency and histoclinical characters of cervical and distant metastases have been assessed, as well as their prognosis factors among 155 patients treated in a curative purpose. RESULTS: 39.1% of the tumours were classified N0, 24.4% N1, 10.7% N2 and 25.8% N3 (UICC 2002). The cervical nodal invasion was significantly more frequent for the classified tumors T3T4 than for the T1T2 (for pyriform sinus, postcricoid esophagus, posterior wall, and total hypopharynx, respectively : P =0.001, P =0.007, P =0.047 and P =0.0005). A cervical lymphatic evidement was preferred in thirty two patients. Among N0, 46.9% were N+; The frequencies of the capsular effraction were not significantly different for the N0N1 from for the N2N3 (P =0.11). The two and five years survival rates were respectively 32.5 and 20.5% for N0, and 10.9% and zero for N3. The survival differences after two and five years between the N0N1 and the N2N3 were significant (P =0.04). A regional failure was noticed for 18.5% of the patients. The tumoral site did not influence significantly the rate of nodal failure (P =0.98), neither the clinical status N (P =0.34). Capsular effraction was a significant factor for the regional failure (P =0.007). Distant metastasis significantly occurred more frequently among the patients initially classified N2N3 than those classified N0N1 (P =0.03), and in case of capsular effraction (P =0.0009). CONCLUSION: Hypopharyngeal squamous cell carcinoma has a high rate of lymph nodes metastasis, correlated to the local extension, and a high rate of occult nodal metastasis. Lymph node clinical status does not seem to have influenced the patients survival; however, capsular effraction constitutes a major prognosis factor of regional failure and distant metastasis. Distant metastases are frequent, particularly in case of wide local and regional tumoral extension.

[Hypopharyngeal squamous cell carcinoma: retrospective study of 149 patients]. / Carcinome épidermoïde de l'hypopharynx: étude rétrospective de 149 traitements à visée curative.

PURPOSE: Hypopharyngeal squamous cell carcinoma is associated to one of the most unfavorable prognosis among the cancers of the head and neck. The purpose of this study is to analyze its therapeutic modalities in the Salah-Azaïz Institute (Tunis) and to compare their results. PATIENTS AND METHOD: This retrospective study concerns 271 hypopharyngeal squamous cell carcinomas, compiled in the Carcinologic Surgery Department of Head and Neck of the Salah-Azaïz Institute over a period of 25 years (from 1977 to 2002). The average age of the patients was of 56 years; sex-ratio was on average of 1.2 (man/woman). The indication of a curative treatment was initially retained for 149 (55%) patients, who were the only ones retained for the analysis of results. RESULTS: We retained the indication of a protocol including surgery and postoperating radiotherapy for 26.2% of the patients. Postoperation mortality rate was 5.1%; the operating rate of morbidity was 46.2%. For 13.5% of the patients, postoperating radiotherapy was permanently interrupted because of a gradual deterioration of the patients' health in the course of treatment. We retained the indication of exclusive radiotherapy for 59.7% of the patients. The average age was of 56 years and the sex-ratio of 1.2. The external radiotherapy was conventional. Radiotherapy had to be permanently interrupted in progress in 32.6% of cases on account of an deterioration of the patients' health; the rate of morbidity of the radiotherapy was 33.3%. We indicated a protocol of conservation of organ with induction chemotherapy for 21 patients (14.1%). The average age was of 53 years (28-65 years) and sex-ratio (man/woman) of 0.5. The global survival was 25.5% at one year, 18.1% at two years, 11.4% at three years and 7.4% at five years. All the patients selected for chemotherapy died in the course of treatment. The rates of survival in two and five years according to protocols surgery-radiotherapy and exclusive radiotherapy were respectively: 21.5 and 12%, and 18.3 and 10%. The difference between the rates of survival of this two protocols is not significant (P =0.08). CONCLUSION: Although the induction chemotherapy entails a particularly high death rate in our series, the association surgery-radiotherapy and the exclusive radiotherapy seem to be similarly efficient for the treatment of the hypopharyngeal carcinoma.

[Therapeutic results of 5-fluorouracil in multiple and unresectable facial carcinoma secondary to xeroderma pigmentosum]. / Résultats thérapeutiques du 5-fluorouracile dans les carcinomes multiples ou non resécables de la face secondaires au xeroderma pigmentosum (XP).

A prospective study was done to test the efficacy of 5-fluorouracil (topical and systemic) in multiple and unresectable histologically proven facial squamous cell carcinomas (SCC) secondary to XP. Twelve patients (7M/5F, mean age 19.8 years) with multiple facial SCC were treated between 1994 and 1997. 5-FU was used as a twice-a-day local application in the documented areas, by continuous infusion associated with cisplatin (2 patients) and short infusion combined with folic acid (3 patients). Evaluation was done by clinical examination every two months for topical therapy and after every cycle for systemic treatment. Median treatment duration was 12 months (2 to 36 months). Treatment was well tolerated excluding episodes of pruritus in the treated areas. We observed mainly superficial tumour regression followed by dryness and crusting. In 5 cases, we performed biopsies after treatment showing in one case an extensive fibrosis with absence of tumour. However in the remaining 4 cases, despite a superficial reduction of tumour and a reconstitution of the epidermis, viable and unmodified squamous cell carcinoma remained in the deeper dermis. In the 5 patients treated by systemic 5-FU, we observed 1 complete response and 3 partial responses. Despite a dissociation between a good cosmetic result and a relatively superficial effect, topical 5-FU represents a useful therapeutic option in multiple unresectable facial SCC in patients with XP. Systemic chemotherapy is recommended in the event of more extended or profound lesions.

[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.

[Cervical lymph node involvement in carcinomas of the mobile tongue in Tunisia. Retrospective study of 135 cases]. / Envahissement ganglionnaire dans les carcinomes épidermoïdes de la langue mobile (CELM) en Tunisie.

OBJECTIVE: To report the profile of histologic cervical nodes involvement associated with mobile tongue squamous cell carcinoma. PATIENTS AND METHODS: Our retrospective study concerned patients treated from 1978 to 1998 by cervical neck dissection for mobile tongue carcinoma. RESULTS: A population of 135 patients (90 M/45 F, sex-ratio 2) with a 53.5 mean age (19 to 75) is analyzed. Clinical palpable nodes were present in 68 cases (50%) mainly submental-submaxillar (54). Histologic examination showed a node involvement in 54 cases without (32 cases) or with capsular rupture (22 cases) mainly in the jugulo-carotidian chain (46/54). Among the 67 clinically N0 patients collected after 1990, 22 patients (33%) exhibited an histological involvement vs 32/68 (47%) for the group presenting palpable cervical nodes for the whole period. Histologic node involvement seemed to be linked to the clinical status, node size and TNM stage. CONCLUSION: Cervical lymph node treatment needs to be systematic in mobile tongue carcinoma. The probability of histologic involvement is linked to the loco-regional extent of disease and influences the prognosis. In N0 patients, neck dissection is required because of the frequency of histological involvement, particularly when loss to follow-up may be expected.

[Metachronous cancers after treatment for undifferentiated nasopharyngeal carcinoma]. / Cancers métachrones après traitement des carcinomes indifférenciés du cavum.

OBJECTIVE: To collect second cancers occurring in the head and neck area after treatment by chemotherapy and/or radiotherapy for undifferentiated nasopharyngeal carcinoma in Tunisia. PATIENTS AND METHODS: This is a retrospective study of patients developing second cancers after treatment for nasopharyngeal UCNT by radiotherapy and/or chemotherapy. To be retained in this study, second tumour had to be histologically different from the initial UCNT, localised in the irradiated area and occurring after a minimal delay of 3 years. RESULTS: We collect 11 cases of second cancers occurring among 2346 patients treated from 1984 to 2001 in Tunisia (0.46%). Patients have been treated for nasopharyngeal UCNT mainly advanced T3-T4 (72%) or N2-N3 (63%). Median age was 20 years (11 to 48) with a sex-ratio of 0.3 (3 M/8 F). Treatment protocol included primary chemotherapy in 4 cases (adriamycin-cisplatin) or adjuvant (in 4) associated to the loco-regional irradiation at a mean dose of 72 Gy (70 to 75). Median delay of second cancer occurrence was 9 years (3 to 17). Tumors were epidermoid carcinomas in 4 cases, fibrosarcomas (2), osteosarcomas (2), glioblastoma (1) and basocellular carcinomas in 2. Second tumors have been treated by surgery alone in 4 cases and chemotherapy alone in 7 patients. No patient have been reirradiated. Median survival was 17 months, 4 patients died and 7 are still alive including 4 in complete remission (24+, 36, 36 and 48+ months) and 3 with progressing disease (8, 16 and 18 months). CONCLUSION: Even very rare, second cancers after treatment for UCNT need to be detected and have a poor prognosis.

[Mucous malignant melanoma of the neck and face. Experience at the Salah Azaiz Institute (Tunis)]. / Mélanomes malins muqueux cervico-faciaux. Expérience de l'Institut Salah Azaiz (Tunis).

The mucosal melanoma of the head and neck is rare and of late diagnosis. This retrospective study concerns 17 cases brought together in 30 years. Sex-ratio was of 1.1, the average age of 58 years. Tumoral seats were the following ones: nasal cavity and paranasal sinus (n = 10), nasopharyngeal cavity (n = 2), gingival seat (n = 2), palate (n = 1), laryngeal seat (n = 1), middle ear (n = 1). Tumoral extension was classified an follows: stage I: 52.9%, stage II: 17.6%, stage III: 29.4%. Melanomas were achromic in 23.5% of cases. On the therapeutic plan, 47.1% of the patients were treated in a purpose palliative because of the importance of the tumoral extension. Seven patients (41.2%) were treated surgically; three among them received an additional radiotherapy for an insufficient tumoral excision or adenopathy in break capsular. Two patients (11.8%) were treated by exclusive radiotherapy. The rates of survival were 17.6% in 2 years, and 5.9% in 5 years. The average duration of survival was of 18.1 months. The causes of failure were essentially local and metastatic.

[Thyroid papillary microcarcinoma. Salah Azaiz Institute experience]. / Microcarcinomes papillaires de la thyroïde. Expérience de l'Institut Salah Azaiz.

The incidence of thyroid papillary microcarcinoma appears to be increasing and therapeutic modalities remain controversial. This retrospective study concerns 25 cases, from 1978 to 1999. The circumstances of diagnosis were: a cervicotomy for thyroid nodule (88% of cases), cervical node metastases (8%), and osseous metastases (4%). The sensitivity of ultrasounds was 22.2%, that of scintigraphy was 9.1% and that of extemporaneous histological examination was 18.2%. Multifocality was found in 16% of cases and bilaterality in 16.6%. Treatment modalities were guided by histological examination. Adjunctive radioiodine ablation was used for 20% of the patients. The treatment of the osseous metastases was completed with external irradiation. The average follow up was 4.8 years (4 months to 19 years), with a rate of survival without disease of 100%.

[Thyroid oncocytomas]. / Les oncocytomes thyroidiens.

OBJECTIVE: Thyroid oncocytomas are rare tumors. They put problems of differential diagnosis enter malignant and benign forms. The modalities of the surgical treatment are controversial, in form as benign as malignant. Their prognosis is also debated. MATERIAL AND METHOD: Our retrospective study concerns 111 thyroid oncocytomas, so 6.5% of thyroid operated in our centre between 1981 and 2001. The sex-ratio of the patients was 0.16 with an average age of 41 years (15 to 72 years). RESULTS: All the fixed nodules, those associated to a recurrential paralysis, to tangible nodes or/and to microcalcifications on the radiography of the neck was malignant. Histological extemporaneous exam was not decisive in 16% of cases, among which 33% showed themselves malignant in the definitive exam, which put in evidence 9 carcinomas (8%). We treated benign oncocytomas by a loboisthmectomy for the isolated nodules, and the subtotal or total thyroidectomy for multinodular glands. For oncocytic carcinomas, we realized a total thyroidectomy with ganglionic taking and histological extemporaneous exam, followed by evidment in case of invasion (2 patients). For the 5 patients having presented a residual fixation, we obtained a white cartography after radioactive iodine administration. For the benign oncocytoma, we did ot notice any recurrences with an average drop of 28 months (2 months to 7 years). For carcinoma, 8 patients on 9 presented an actuarial survival without disease with an average drop of 44 months (18 months to 8 years). CONCLUSION: The diagnosis of malignancy of thyroid oncocytomas can be strongly evoked on however fickle clinical and radiological criteria; it can be eliminated only after definitive anatomo-pathological exam.