Garlic (Allium sativum) feeding impairs Sertoli cell junctional proteins in male Wistar rat testis: microscopy study.

Sertoli cell junctions, such as adhesion junction (AJ), gap junction (GJ) and tight junction (TJ), are important for maintaining spermatogenesis. In previous studies, we showed the inhibitory effect of crude garlic (Allium sativum, As) on spermatogenesis and steroidogenesis. The aim of this work was to complete our investigation on the impact of this plant, especially on Sertoli cell junctional proteins (SCJPs). During 1 month, 24 male rats were divided into groups: group control (0% of As) and treated groups fed 5%, 10% and 15% of As. Light and electron microscopy observations were performed to localise junctional proteins: connexin-43, Zona Occluding-1 and N-cadherin (immunohistochemistry) and to describe junctions. We showed that the specific cells involved in the localisation of the SCJP were similar in both control and treated groups, but with different immunoreactivity intensity between them. The electron microscopy observation focused on TJs between Sertoli cells, constituting the blood-testis barrier, showed ultrastructural changes such as fragmentation of TJs between adjacent Sertoli cell membranes and dilatation of rough endoplasmic reticulum saccules giving an aspect of scale to these junctions. We concluded that crude garlic consumption during 1 month induces perturbations on Sertoli cell junctions. These alterations can explain apoptosis in testicular germ cells previously showed.

Prise en charge des cancers primitifs des glandes submandibulaires

Introduction :Les tumeurs malignes de la glande submandibulaire se caracterisent par une grande diversite histologique. de ce travail est de rapporter notre experience dans la prise en charge de ces tumeurs et de suggerer une attitude therapeutique apres revue de la litterature. Patients et methode : Il s'agit d'une etude retrospective a propos de 20 patients colliges sur 17 ans. La decision therapeutique etait prise au sein d'un comite multidisciplinaire. Les moyens therapeutiques etaient la chirurgie tumorale et ganglionnaire; la radiotherapie et la chimiotherapie. Les pieces operatoires ont ete adressees pour examen anatomopathologique extemporane et definitif. Une surveillance clinique et radiologique a ete realisee. Le recul moyen etait de 35 mois. Resultats: L'age moyen etait de 60;75 ans. Le delai moyen de consultation etait de 6;15 mois. La tumefaction submandibulaire etait le motif de consultation chez tous les patients. Des adenopathies cervicales etaient notees chez 8 patients (40). Seize patients avaient beneficie d'une tomodensitometrie cervicale et du massif facial et un autre d'une Irm. La radiographie du thorax montrait un aspect de lacher de ballon chez un patient et une opacite mediastinale chez un autre. L'abstention chirurgicale avait ete decidee pour 2 patients. Les patients metastatiques ont ete operes uniquement dans un but diagnostique. Dix-huit patients (85) ont eu une submandibulectomie; dont une elargie a la mandibule. Pour le geste ganglionnaire; 11 patients ont eu un curage selectif triangulaire et 3 un curage fonctionnel complet. Une radiotherapie postoperatoire a ete realisee chez 14 patients (70). Une radiotherapie palliative isolee a ete realisee chez 2 patients. Une chimiotherapie palliative a ete indiquee chez les 2 patients presentant des metastases a distance lors du diagnostic; mais n'a ete administree que dans un cas. La remission complete etait notee dans 11 cas (55). Un seul patient avait presente une poursuite evolutive. Une recidive loco-regionale avait ete decelee chez 2 patients. Deux patients avaient developpe secondairement des metastases a distance. Le taux de mortalite dans notre serie etait de 25. Conclusion: Les cancers de la glande submandibulaire representent une pathologie peu frequente. Le diagnostic a grandement beneficie de l'apport de l'imagerie. La strategie therapeutique depend du stade tumoral au moment du diagnostic et de l'etat general du patient. Le pronostic de ces tumeurs reste toujours reserve; surtout pour les tumeurs de haut grade diagnostiquees a un stade avance

The effect of methylation on some biological parameters in Salmonella enterica serovar Typhimurium.

Cell growth is tightly coupled to DNA replication and its methylation [Proc Natl Acad Sci U S A 93 (1996) 12206-12211]. In a culture medium, growing of Salmonella Typhimurium (S. Typhimurium) mutant cells (dam⁻) decreased (2.5 fold) relative to the wild type strain (dam⁺). In this study, we show that the reason for this growth deficiency is due to the DNA methylation. The absence of a Dam methyltransferase protein results in poor growth efficiency and disturbs the synchrony of replication initiation in vivo, as evaluated by flow cytometry. On the other hand, we show that lack of methylation could increase the DNA response to thermal stress (decreasing the DNA melting temperature, T(m)), and the reason for this effect is due to the methylation status and not to the number of guanine and cytosine bases (G+C) in the duplex DNA. Our results show that methylation is an epigenetic factor that may play a key role in the cell growth, the synchrony of DNA replication [C R Biologies 330 (2007) 576-580] and the stress protection.

[Sarcomatoid carcinomas of the upper airways]. / Carcinomes sarcomatoïdes des voies aéro-digestives supérieures.

INTRODUCTION: The sarcomatoid carcinoma of the superior aerodigestive tracts is a rare malignant tumour which presents diagnostic and therapeutic challenges. MATERIAL AND METHOD: We report 11 cases of spindle cell carcinomas of the upper airways. RESULTS: Sex-ratio was 10:1 and the mean age was 57.3 years (30 - 75 years). Nine patients were smokers and 4 presented with a history of radiation exposure. Tumoral locations were as follows: larynx: 6, hypopharynx: 1, oropharynx: 1, nasopharynx: 1, oral cavity: 2. Histological diagnosis in 3 cases required the use of immunohistochemical studies. Four patients were first seen at an advanced stage. This left 9 patients and among them 7 received a curative treatment: 5 by surgery alone, 1 by surgery and radiotherapy, 1 by radiotherapy, 1 by chemo-radiotherapy for the nasopharyngeal lesion and 1 by chemotherapy alone. Two patients died from their disease before treatment. With an average delay of 15.4 months, the rates of global survival and disease-free were 5/9 and 4/9 respectively. CONCLUSION: The sarcomatoid carcinoma of the upper airways is rare, but not unusual. Its diagnosis benefits from progresses in immunohistochemistry, but also from advances in the field of molecular biology. Its treatment and natural evolution remain controversial.

Matrix-producing breast carcinoma: a case report of this rare entity.

Matrix-producing carcinoma of the breast is very rare with few cases reported in the literature. This entity is characterized by the association of malignant epithelial elements and a mesenchymal component. Therapeutic strategy is not well established and prognostic factors need further research. We report here a case of matrix-producing carcinoma in a 46-years-old woman who presented with a large lump in her left breast. A core biopsy concluded to an invasive carcinoma but neoadjuvant chemotherapy was not helpful. Diagnosis of matrix-producing carcinoma was done on the lumpectomy specimen after excision of the fast-growing mass. Immunophenotypic profile was very suggestive showing tumoral cells positivity for cytokeratins, epithelial membran antigen and S-100 protein. One year later, the patient developed lung metastases.

Evaluation et prise en charge de l'envahissement mandibulaire dans les carcinomes epidermoides de la cavite orale et de l'oropharynx

Objectif : Le but de notre etude est l'evaluation de l'atteinte mandibulaire dans les carcinomes epidermoides de la cavite orale et de l'oropharynx. Materiel et methodes : Il s'agit d'une etude retrospective a propos de 34 patients colliges sur 6 ans (1999-2004) et ayantun carcinome epidermoide de la cavite orale et/ou de l'oropharynx avec envahisse- ment mandibulaire confirme a l'anatomopathologie.L'atteinte mandibulaire a ete evaluee par l'examen clinique; l'orthopantomographie; la tomodensitometrie; et par les constata- tions peroperatoires du chirurgien. Tous les patients ont eu un evidement ganglionnaire; une exerese tumorale associee a une mandibulectomie segmentaire interruptrice ou conservatrice. Resultats : L'envahissement mandibulaire a ete suspecte cliniquement chez 70;5des patients devant l'adherence de la tumeur a l'os. Apres examen clinique et imagerie; cette atteinte a ete diagnostiquee chez 88;2des patients. Dans 11;8des cas; l'atteinte n'a ete suspectee qu'en peroperatoire. L'examen histologique a confirme l'atteinte osseuse chez tous les patients. La mandibulectomie segmentaire a ete pratiquee chez 17 patients devant l'atteinte du canal mandibulaire. Vingt-huit patients ont eu une radiotherapie postoperatoire a la dose moyenne de 64 Gy. Les taux de recidive; de metastase et de deces etaient respectivement de 11;7; 17;6et 17;6pour les patients qui ont eu une mandibulectomie segmentaire; et de 23;5; 17;6et 23;5pour ceux qui ont eu une mandibulectomie conservatrice. Par ailleurs; 76;5et 29;5 des patients ayant eu respectivement une mandibulectomie segmentaire et une mandibulectomie conservatrice avaient une gene fonctionnelle importante lors de l'alimentation.Conclusion : L'examen clinique; l'imagerie et l'examen peroperatoire sont d'un apport capital dans l'evaluation de l'atteinte mandibulaire. Une atteinte epargnant le canal mandibulaire justifie une mandibulectomie conservatrice permettant d'avoir de meilleurs resultats esthetiques et fonctionnels tout en assurant un controle carcinologiquement satisfaisant

Les cancers de l'orbite et l'etude retrospective : a propos de 31 cas

Introduction : Les cancers de l'orbite sont rares. Ils sont caracterises par leur diversite histologique et leur agressivite locoregionale rendant le traitement difficile et mutilant. Dans ce travail; nous rapportons notre experience dans la prise en charge diagnostique et therapeutique de ces tumeurs. Materiels et methodes : Notre etude retrospective a concerne 31 cas de cancers de l'orbite colliges sur 13 ans (1993- 2005). Tous les patients ont beneficie d'un examen clinique complet; d'une imagerie du massif facial (TDM et/ou IRM) et d'une biopsie de la tumeur. Le traitement a ete base sur la chirurgie; la radiotherapie et/ou la chimiotherapie. Resultats : La symptomatologie clinique etait dominee par les signes ophtalmologiques et les algies faciales. L'imagerie a montre dans tous les cas un processus expansif tissulaire a point de depart orbitaire; avec lyse osseuse orbitaire chez 16 patients (51;6); une extension au massif facial chez 7 patients (22;6); endocraniennes chez 6 patients (19;4) et des formes bilaterales atteignant les deux orbites dans 3 cas (9;7) L'anatomopathologie montrait une predominance des lymphomes malins non hodgkiniens (32;3) et des carcinomes epidermoides (32;3); suivis des rhabdomyosarcomes embryonnaires (19;4). Douze patients ont ete traites par chirurgie et radiotherapie postoperatoire; dix patients par une association radio-chimiotherapie; et neuf autres par une chimiotherapie neo-adjuvante. La survie globale etait de 67;8 a 3 ans; 48;4 a 5 ans et 22;6a 10 ans

[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.

Chronic iodine overload and apoptosis in cold nodules from endemic multinodular goiters.

As apoptosis and necrosis are known to exist during experimental goiter development and involution, we studied them in ten Tunisian multinodular endemic goiters, five of them having received a chronic excess of iodine during six months. Apoptotic thyrocyte nuclei have been counted on hematoxylin-eosin stained semi-thin sections. Using immunoperoxidase on paraffin sections, bcl-2 and bax immunoreactivities have been evidenced, and CD34 positive microvessels counted; ultra-thin sections have also been observed. After six months of iodine overload, apoptotic thyrocytes were ten times more numerous; CD34 positive endothelial cells were diminished by one half bcl-2 immunoreactivity disappeared in thyrocytes and a bax one appeared in thyroid follicular and endothelial cells. Presence of numerous apoptotic follicular and endothelial cells was confirmed using electron microscopy. Chronic iodine excess induces apoptosis and necrosis of thyroid follicular and endothelial cells, leading to thyroglobulin accumulation in connective tissue.

[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.

[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%.

[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.

[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.

Association between HLA-A/-B antigens and -DRB1 alleles and nasopharyngeal carcinoma in Tunisia.

Using serologic and molecular methods, 45 nasopharyngeal carcinoma (NPC) patients were typed for HLA class I and class II and were compared to 100 unrelated normal Tunisians. Our results showed that the antigen frequency of HLA-B13 and allelic frequencies of DRB1*03, DRB1*15 were significantly higher in the NPC patients than in the control group (15.5 vs. 4; 26.4 vs. 11.5, and 14.4 vs. 6.5%, respectively) probably indicating a positive association with NPC. Moreover, we observed that HLA-A23 was absent in our NPC sample and was present in 18% of normal controls, and HLA-DRB1*11 was less frequent among the patients compared to the controls (5.5 vs. 14%) suggesting a protective effect of this association with NPC.