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Objectives: Tobacco and alcohol are the main etiological factors common to laryngeal cancers. However, the Human Papilloma Virus (HPV) constitutes an alternative risk factor according to several studies. In Tunisia, despite the annual increasing incidence of laryngeal squamous cell carcinoma (LSCC), the prevalence and prognostic significance of HPV have never been explored. In this study, we sought to highlight HPV DNA in 70 biopsies of laryngeal cancer, and to analyze the status of HPV infection in association with p53, p16, survivin, and IGF-1R expressions. Methods: HPV high risk (HPV HR) DNA was detected in tumors by in situ hybridization. However, the expression of p53, p16, survivin and IGF-1R were stained by immunohistochemistry test. The correlations of HPV status with clinicopathological parameters, overall survival, disease-free survival and proteins expressions were statistically evaluated. Results: HPV HR DNA was detected in 39 out of 70 (55.71%) laryngeal tumors. HPV+ patients have a better overall survival ( P = .081) and long disease-free-survival ( P = .016) with a low rate of recurrence ( P = .006) than HPV– patients. No significant correlations were found between HPV HR status and clinicopathological parameters (all P > .005). Moreover, HPV+ tumors were not associated with expression of p53, p16 and survivin. However, HPV HR status correlates with weak to moderate IGF-1R expression ( P = .043). Conclusion: The substantial detection of HPV HR in LSCC tumors suggest that this virus plays an important part in laryngeal cancer in Tunisia. It is a good prognostic factor. In addition, HPV infection could act to block the pathway of IGF-1R expression.

The aim was to evaluate the clinical impact of IGF-1/IGF-1R in Tunisian laryngeal carcinoma. A high IGF-1R immunohistochemical expression was found in our series (81.43%). A tendency toward an association between IGF-1R expression and lymph node metastasis was found (

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.IGF-1 levels was measured by Elisa test among 82 NPC patients and 60 healthy controlsOur results showed, for the first time, a significant increased levels of IGF-I in NPC by in comparison with healthy controls (p0.01). 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 (p0.01). The IGF-1 levels are, also, higher among women compared to men (p0.01). The concentrations of IGF-1 were positively correlated with tumor size of NPC patients (p0.01).IGF-I could be a good nasopharyngeal cancer diagnostic marker.

Purpose The pathogenesis of psoriasis is characterized by a disruption of extracellular matrix (ECM) in which matrix metalloproteinases (MMPs) participate actively. We aimed to determine MMP-7 level and its association with the inflammatory response in order to determine its usefulness as a biomarker for psoriasis prediction. We also aimed to determine its distribution in uninvolved and involved psoriatic skin to evaluate the probable role of MMP-7 in psoriasis pathogenesis. Materials and methods We recruited 108 psoriatic patients and 133 healthy controls. MMP-7, tissue inhibitors of metalloproteinases (TIMPs) and interleukin-6 (IL-6) levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) assay. MMP-7 expression was detected by Immunohistochemistry (IHC) study. Results ECM turnover and inflammatory biomarker levels were significantly higher in psoriatic patients. MMP-7 revealed to be independently associated to psoriasis even after adjustment for different models. The area under the curve (AUC) of MMP-7 and inflammation Z-score were similar. MMP-7 was positively correlated with IL-6 and inflammation Z-score. Psoriasis severity (PASI) was correlated significantly with IL-6 (p = 0.007). The MMP-7 expression was detected in the epidermis of involved and uninvolved psoriatic skin. In involved skin, MMP-7 was expressed by basal and mostly suprabasal keratinocytes. In uninvolved skin, expression of MMP-7 was restricted to basal keratinocytes. Conclusion MMP-7 is independently associated to psoriasis disease and to inflammatory response which make it a potential biomarker for this dermatosis.

The objective of this study was to evaluate the expression of survivin and p16 in laryngeal squamous cell carcinoma (LSCC) in order to analyze their pathogenesis and prognostic significance in Tunisian patients. A total of 70 patients with LSCC collected at the Salah Azaiez Cancer Institute of Tunis were retrospectively evaluated. Expression of survivin and p16 was examined using immunohistochemistry, and the correlations with clinicopathological parameters, overall survival (OS), and disease-free survival (DFS) were statistically evaluated. The positive expression of survivin and p16 were found in 58.6% and 51.43% of LSCC cases, respectively. The p16 expression was not associated with either clinical parameters or patient survival, whereas there was a strong correlation of survivin expression and lymph node metastases ( P = .002), alcohol consumption ( P = .024), and therapeutic protocol (with or without chemotherapy; P = .001). Kaplan-Meier survival curves showed that patients with LSCC having positive survivin expression have shorter OS ( P = .026) and shorter DFS ( P = .01) than those with negative expression. Positive survivin expression was also correlated with high recurrence rate ( P = .014). Therefore, survivin is a poor prognostic marker for LSCC but the therapeutic protocol remains, in multivariate study, the most decisive for the OS and DFS of our patients with P < .01. Our data indicated that, in Tunisian laryngeal squamous cell carcinoma, survivin expression is associated with unfavorable outcomes and represents a predictor marker of recurrence and chemoresistance. However, p16 expression has no prognosis value.

The purpose of this study was to evaluate the effects of 6 months of specific balance training included in endurance-resistance program on postural balance in haemodialysis (HD) patients.Forty-nine male patients undergoing HD were randomly assigned to an intervention group (balance training included in an endurance-resistance training, n = 26) or a control group (resistance-endurance training only, n = 23). Postural control was assessed using six clinical tests; Timed Up and Go test, Tinetti Mobility Test, Berg Balance Scale, Unipodal Stance test, Mini-Balance Evaluation Systems Test and Activities Balance Confidence scale.All balance measures increased significantly after the period of rehabilitation training in the intervention group. Only the Timed Up and Go, Berg Balance Scale, Mini-Balance Evaluation Systems Test and Activities Balance Confidence scores were improved in the control group. The ranges of change in these tests were greater in the balance training group.In HD patients, specific balance training included in a usual endurance-resistance training program improves static and dynamic balance better than endurance-resistance training only. Implications for rehabilitation Rehabilitation using exercise in haemodialysis patients improved global mobility and functional abilities. Specific balance training included in usual endurance resistance training program could lead to improved static and dynamic balance.

Summary Aims The objective of this study was to compare the protein expression profile between well-differentiated (papillary) and undifferentiated (anaplastic) thyroid carcinoma in Tunisian patients. Methods This first Tunisian retrospective study concerned data of 38 thyroid cancer cases (19 papillary carcinoma PTC and 19 anaplastic carcinoma ATC) collected at Salah Azaiez Institute of Tunisia. Immunohistochemistry was used to evaluate tumor expression of different molecular markers (p53, Ki67, E-cadherin, cyclin D1, bcl2, S100 and Her-2). The molecular expression was correlated with the clinicopathological characteristics of the tumors. Results There were 6 differentially expressed markers when comparing anaplastic thyroid carcinoma ATC with papillary thyroid carcinoma PTC. Expression of p53 and Ki67 were significantly increased in 16 and 18 ATC cases respectively, the Ki67 expression was lost in PTC. Cyclin D1, E-cadherin, bcl2 and S100 were overexpressed in PTC tumors; however, they were significantly decreased in ATC. The last marker, Her-2 was expressed in one case of PTC only. Conclusion Our results, similar with findings of other ethnic groups, showed alteration in expression of molecular markers associated with tumor dedifferentiation, indicating loss of cell cycle control with increased proliferative activity in ATC carcinoma. These data support the hypothesis that ATC may derive from dedifferentiation of preexisting PTC tumor.

Because nasopharyngeal carcinoma (NPC) has a close association with Epstein-Barr virus (EBV), measuring serum EBV DNA and anti-EBV serum marker concentrations could be a feasible method for NPC diagnosis, monitoring and probably screening especially in a community at risk. The aim of this study was to determine the EBV pattern in sporadic NPC and in high risk NPC Tunisian families in order to evaluate their risk factors and help for NPC screening. The rates of anti-EBV antibodies and EBV DNA were determined in the serum of 47 healthy members randomly selected from 23 NPC multiplex families with two or more affected members, 93 healthy Tunisian community controls chosen with the same age, sex and geographic origin as unaffected individuals and 66 EBV positive sporadic NPC patients whose serum was available before and after treatment. Unexpectedly, significant lower concentrations of anti-EA (Early Antigen) IgG and anti-VCA (Viral Capsid Antigen) IgG were found in unaffected members from NPC families than in healthy controls while viral loads were negative in all the tested sera. For sporadic NPC patients, anti-EA IgG and anti-VCA IgA concentrations were significantly higher than in healthy controls and these rates decreased after treatment. The level of EBV DNA load varied according to the condition of the tumour. This study suggests that in the Tunisian NPC families, screening for malignancy is based on serum concentrations but not on EBV DNA load while in the sporadic NPC group, serologic markers and EBV DNA load are complementary for diagnosis and follow-up.

The aim of this study was to describe the clinico-epidemiological and histopronostic characteristics of triple negative breast cancer (TNBC) and to evaluate the therapeutic results in tunisian women.We reported the results of a retrospective study including 90 patients treated for TNBC between Junuary 2008 and December 2009 in the Salah Azaiz Institute of Tunis.TNBCoccured in 14% of diagnosed breast cancers. The mean age at diagnosis was 53.67 years. Family history of breast cancer was reported in 10% of cases.The majority of tumors were classified as T2 (41%) and associated with invasive ductal carcinoma histological type (99%) and SBR grade-II (54%). Tumor lymph node metastases were detected in 44% of patients.Among operated patients, 46% of patients underwent conservative surgery and 54% radical surgery. Chemotherapy and postoperative radiotherapy were given in97% and 80%of patients, respectively. After a median follow-up of 33.51 months, 61% of patients remained free of disease, 12% hadloco-regional recurrence, 9% had disease progression during chemotherapy and 21% developed systemic disease.TNBC diagnosis is often made in the advanced stage and has a tendency to recur after treatment. The variable responseto chemotherapy is due to the molecular tumor heterogeneity. The development of targeted therapies is necessary to improve outcome of chemoresistant TNBC.

The evaluation of the proliferation in the mammary carcinomas provides useful prognostic and predictive information for subsequent management. The purely morphological evaluation of proliferative activity was represented by the evaluation of mitotic index. New analytical methods were gradually developed and performed. Among these methods, evaluation of Ki67 by immunohistochemistry is particularly interesting. Its expression is significantly increased in the cell cycle.To correlate the mitotic index as a classic method of assessing cell proliferation and Ki 67 proliferation index detected by immunohistochemistry to identify the most reliable proliferative marker.We studied 200 patients with invasive ductal carcinoma breast over a period of 12 months of 2014. We identified in each case the SBR grade, Ki67 proliferation index and the mitotic index. Correlation between the two parameters was identified using the Spearman test. A result is considered significant when p0.01. The distribution of these markers by SBR gradewas studied using the ANOVA method.Ki67 is significantly correlated to the mitotic index. Although these two methods are dependent, Ki67 is the most sensitive and bonded to SBR grade. Determination of Ki67 provides interesting information that could replace the mitotic account. It provides reliable and reproducible data that can be incorporated into a prognostic score.Ki67 is a more efficient marker mitotic index, reflecting the cell proliferation.

Mucinous carcinoma is a particular type of breast cancer characterized by the presence of extracellular mucin and is linked with a more favorable prognosis than invasive breast carcinoma of no special type. It accounts for 1 to 7% of all breast cancers. We propose in this work to study at first the clinic-pathological characteristics and the evolution of 48 cases of mucinous carcinomas. Secondly, we propose to identify through a review of recent literature, the therapeutic management of these carcinomas.This is a retrospective study, conducted in Salah Azaiez carcinological institute, interesting 48 cases of mucinous carcinoma collected over 19 years. Clinical, radiological and pathological information were collected from medical records.The mean age of our patients was 57 years. The tumor was single in 41 cases and in 7 cases bifocal. Mammographic aspects were favor of malignancy in 33 cases (75%). It was mixed subtype in 14 cases and pure in 34 cases. Lymph node involvement was noted in 14 cases. The number of metastatic lymph nodes ranged from 1 to 11 with an average of 3. Hormone receptors were positive in 35 tumors (73%). The HER2 showed overexpression in 5 cases. Surgery consisted of a radical treatment for thirty-two patients (66%). Overall survival at 5 years was 75.3% and 59.3% at 10 years. Disease-free survival was 74% at 5 years and 58% at 10 years.Mucinous carcinoma consists of two distinct subtypes: pure and mixed with different prognosis. Larger data samples with longer follow-up are necessary to achieve an improved understanding of this particular tumor.

Background In the Tunisian population, as yet a limited number of BRCA1/2 germline mutations have been reported in hereditary breast and/or ovarian cancer. These mutations are located in a few exons of BRCA1/2 . The aim of the present study was to search for these mutations in 66 unrelated patients with hereditary breast and/or ovarian cancer in order to assess the interest in such a targeted approach for genetic testing in Tunisia. Materials and Methods Blood specimens from the 66 Tunisian patients, with family history of breast and/or ovarian cancer, were collected at the Salah Azaiz Cancer Institute of Tunis. The exons 5, 20 and part of exon 11 of BRCA1 as well as part of exons 10 and 11 of BRCA2 were analyzed by Sanger sequencing. Results 12 patients had deleterious mutations in the BRCA1 or BRCA2 genes (18%), including a novel frame-shift mutation of BRCA1 (c.3751dup; 3780insT). Four distinct BRCA1 mutations were detected eight patients: c.5266dup (5382insC) and c.211dup (330insA) each in three patients, c.3751dup (3870insT) and c.4041_4042del (4160delAG) each in one patient. The four remaining cases all carried the same BRCA2 mutation, c.1310_1313del (1538delAAGA). Besides these deleterious mutations, eight polymorphisms and unclassified variants were detected, one of them being never reported ( BRCA1 c.3030T>G, p.Pro1010Pro). Conclusion In this study, we show that targeting relevant exons in BRCA1 and BRCA2 genes allows detection of a substantial percentage of mutations in the Tunisian population. Therefore such an approach may be of interest in genetic testing of high-risk breast and ovarian cancer families in Tunisia.

We measured the 127I distribution within tyroid tissue to find out where intrathyroid iodine was deposited during iodine treatment in eight Tunisian female patients (aged 33-58 yr) with endemic euthyroid goiter. Before surgery, five patients were treated during 6 months either by Lugol's solution (group 1: three patients) or by Lugol's and L-thyroxine (group 2: two patients). All patients remained euthyroid during the course of the treatment, which supplied 3.8 mg/day iodine. Three other patients did not receive Lugol's solution (control group). Secondary ion mass spectrometry microscopy was used to map 127-I quantitatively on thyroid sections. Specimens obtained at thyroid surgery were divided macroscopically into nodular and extranodular tissue and chemically fixed to preserve organified iodine. The iodine profile of patients in group 1 did not differ from that in group 2: large amounts of iodine were localized in thyroid follicles and stroma of both nodular and extranodular tissues. In the control group, iodine within stroma was found only in the extranodular tissue. Despite the limited number of patients studied, these data suggest that stromal iodine might represent a storage compartment in times of large iodine supply.

The objective is to report the correlation between pathology and molecular subtype classifications of breast cancer in Tunisian women.This retrospective study concerned data of 966 breast cancer cases collected from 2007 to 2009 at Salah Azaiz Institute of Tunis. These cases were classified by an immunohistochemistry test for estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2) status in the four molecular subtypes, namely luminal A, luminal B, HER2+ and triple negative. The molecular classifications were correlated with the clinicopathological characteristics of the tumors.Luminal A (50.7% of cases) was the most common subtype, with triple negative subtype 22.5%, luminal B 13.4% and HER2+ 13.4%. Triple negative and HER2+ subtypes were significantly associated with large tumor size (5 cm, P 0.001), younger age (40 years, P 0.03) and high grade (P 0.001). Conversely, there was no correlation with the lymph node status.Our data demonstrated that the luminal A subtype, associated with a favorable prognosis, was the most frequent subtype in the Tunisian population; however the triple negative subtype occurred at a high incidence in Tunisia compared to Western countries. The molecular subtypes are correlated to the tumor size, histological grade and patient's age.

European Annals of Otorhinolaryngology, Head and Neck Diseases - Vol. 133 - N° 1 - p. 63-64

BACKGROUND Limited sampling strategies (LSS), using few sampling times after dosing, have been used to reliably predict tacrolimus area under the 12-hour concentration-time curve (AUC). Because the pharmacokinetics of tacrolimus is subject to significant changes over the exposure time to this drug, it can be hypothesized that the reliability of the LSS would also change. This study aimed to develop a reliable and practical LSS allowing the estimation of tacrolimus AUC in Tunisian kidney transplant recipients taking into account the posttransplantation time. METHODS Thirty Tunisian patients were enrolled into 3 groups (10 in each group) according to the posttransplantation period: period 1: between 1 day and 3 months, period 2: between 3 and 12 months and period 3 over 12 months, as defined by the European consensus conference on the therapeutic drug monitoring of tacrolimus. Samples were collected just before and 0.5, 1, 2, 4, 6, 8, and 12 hours after tacrolimus administration. The full pharmacokinetic profiles obtained from these timed concentration data were used to choose the best sampling times. Error indices (mean absolute prediction error and the root mean squared prediction error) were used to evaluate the predictive performance. RESULTS Among the 1-point estimations, the C4-predicted AUC showed the highest correlation with the measured one during period 1 and period 2 (r = 0.94 and 0.91, respectively) but not period 3 (r = 0.76). The C0-predicted and the measured AUC become less and less correlated from period 1 to period 3 (r = 0.81, 0.75, and 0.66), respectively. Only the model including the C0/C2 provided a high correlation between predicted and measured tacrolimus AUC regardless of the posttransplant period (r = 0.95, 0.96, 0.98 and root mean squared prediction error = 4.1, 5.8, 4.2 during periods 1, 2, and 3, respectively). CONCLUSIONS Our data clearly indicate that the predictive performance of LSS is prone to change according to the posttransplantation time. A 2-time point LSS was found to be sufficient to predict tacrolimus AUC. The LSS using C0 and C2 is reliable, accurate, and practical to estimate the AUC of tacrolimus regardless of the posttransplantation time.

Oral tongue cancer remains an aggressive tumour in Tunisia, and patients often present with locally advanced disease, leading to high mortality. The molecular pathway of its tumorigenesis is not yet understood. This study aimed to assess the biologic significance of p53, heat shock protein 70 (Hsp70), Ki67, and CD34 and their influence on survival in patients with tongue cancer.Archival tissues from 68 patients with squamous cell carcinoma of the tongue were examined for p53, Hsp70, Ki67, and CD34 by immunohistochemistry and correlated with 5-year survival.p53 and Ki-67 were detected in 55% and 77% of tumours, respectively; a significant association between p53 and Ki67 expression was found (p = .038). Forty-seven percent of cases of tongue cancer expressed Hsp70, and only 9% of tumours expressed CD34 angiogenic factor. No significant correlation was noted between survival and expression of p53, Hsp70, Ki67, and CD34 in patients.None of the markers p53, Hsp70, Ki67, and CD34 demonstrated prognostic significance for 5-year survival in patients with squamous cell carcinoma of the tongue.

Angiogenesis is a significant prognostic factor in breast cancer, but the factors that control angiogenesis in vivo are not well defined.The purpose of this study was to investigate P53 expression in breast cancer and to examine the relationship between P53 overexpression and the degree of angiogenesis.A total of 52 paraffin-embedded tumors were evaluated immunohistochemically for expression of P53 and CD34 angiogenesis factor.The majority of P53 positive cases (82%) demonstrated high level of microvessel density (MVD); 18% demonstrated no CD 34 expression. In contrast there was no variation of CD34 expression among P53 negative tumors.This data suggests that microvessel density is promoted by P53 overexpression in breast cancer, and is correlated with high histologic grade.

We aimed to develop an accurate and convenient LSS for predicting MPA-AUC(0-12 hours) in Tunisian adult kidney transplant recipients whose immunosuppressive regimen consisted of MMF and tacrolimus combination with regards to the post-transplant period and the pharmacokinetic profile. Each pharmacokinetic profile consisted of eight blood samples collected during the 12-hour dosing interval. The AUC(0-12 hours) was calculated according to the linear trapezoidal rule. The MPA concentrations at each sampling time were correlated by a linear regression analysis with the measured AUC(0-12). We analyzed all the developed models for their ability to estimate the MPA-AUC(0-12 hours). The best multilinear regression model for predicting the full MPA-AUC(0-12 hours) was found to be the combination of C1, C4, and C6. All the best correlated models and the most convenient ones were verified to be also applicable before 5 months after transplantation and thereafter. These models were also verified to be applicable for patients having or not the second peak in their pharmacokinetic profiles. For practical reasons we recommend a LSS using C0, C1, and C4 that provides a reasonable MPA-AUC(0-12 hours) estimation.

The determination of ochratoxin A (OTA) in human blood in Tunisian populations is underway. The range of conta mination is between 0.7 to 7.8 ng ml-1 for the general popu lation and 12 to 55 ng ml-1 for people suffering from chron ic renal failure. It appears that 21 to 64% of people suffer ing from nephropathy are OTA positive with a detection limit of 1ng ml-1. This situation prompted us to search for possible association of OTA contamination and nephropa thy resembling Balkan endemic nephropathy. The classifi cation of the ill population into chronic interstitial nephropathy (CIN), chronic glomerular nephropathy (CGN), chronic vascular nephropathy (CVN) and others, indicated that the largest is the CIN group which is signifi cantly different from the other groups, and from the con trol (P < 0.005). Furthermore, it presented the highest OTA mean values (25 to 59 ng ml-1) compared with the control, CGN, CVN and other groups (6 to 18 ng ml-1) according to the designated region in Tunisia. The rural population seems to be more exposed to ochratoxins in Tunisia, as has been previously reported in the Balkans and Western Europe. Altogether, these results emphasise that in Tunisia an endemic ochratoxin-related nephropathy is probably occurring.

Le mélanome muqueux primitif de la fosse nasale est une tumeur maligne très agressive, rare, constituant 1% de l'ensemble des mélanomes. Sa symptomatologie est non spécifique et son diagnostic est anatomo-pathologique, appuyé par l'immunohistochimie. Son traitement est essentiellement chirurgical basé sur une résection large de la tumeur. Le pronostic est défavorable, caractérisé par des récidives et des métastases fréquentes et un taux de survie bas. Nous rapportons dans ce travail un nouveau cas de mélanome malin primitif de la fosse nasale, tout en précisant les caractéristiques de cette tumeur.

Inflammatory myofibroblatic tumor is a recently caracterized solid mesenchymal tumor. They are frequently localised in the lung. However, the head and neck forms are uncommon.To report a new case of inflammatory myofibroblastic tumor of the larynx.This 47-year old man presented with dysphonia without dyspnea. Laryngoscopy showed a tumor of anterior vocal cord. CT scan of larynx confirmed diagnosis. The patient had a cordectomy. Histology concluded to the diagnosis of inflammatory myofibroblastic tumor. No relapses have been noted after 4 months.Only a few cases of laryngeal inflammatory myofibroblastic tumor have been reported in the literature. Clinical presentation depends of tumor location. Radiological images are not specific and diagnosis is based on histology. The expected course is essentially marked by the risk of local recurrences. Surgical excision seems to be the treatment of choice.

The sarcomatoid carcinoma of the superior aerodigestive tracts is a rare malignant tumour which presents diagnostic and therapeutic challenges.We report 11 cases of spindle cell carcinomas of the upper airways.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.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.

The aim of this review is to study natural history, presentation, treatment and prognosis of head and neck liposarcomas.We carry a retrospective study about 15 patients diagnosed and treated in our department between 1969 and 2001. Therapeutic modalities included surgery, radiotherapy and chemotherapy.Tumors were mostly localized at the neck (4 cases) and the scalp (3 cases). Cervical lymphadenopathy was found in 1 case. Chest X-ray found showed metastases in 2 cases. Histological types of liposarcomas were the following: myxoid (5 cases), well differentiated (4 cases), pleomorphic (4 cases), round cell (1 case) and dedifferentiated (1 case). Twelve patients underwent surgery. Complete excision was performed in 7 cases. In the other 5 cases, exeresis was incomplete and 4 of them received postoperative radiotherapy. Three patients were not operated because of vascular involvement (1 case) or metastasis (2 cases), and they all received radiotherapy alone. After initial treatment, complete remission was achieved in 7 cases (46.7%). A recurrence occurred in 8 cases (53.3%). Two of these patients were reoperated and another one received chemotherapy. In the other 5 cases, the tumor was uncontrollable and no additional treatment has been proposed. Five-year survival rate was 87% for patients who underwent surgery alone, 75% for those who underwent surgery and postoperative radiotherapy, and 0% for those treated by radiotherapy alone.The mainstay of treatment of head and neck liposarcomas is surgical excision and the prognosis is largely determined by the histological grade and the clinical stage.

Renal transplant recipients are at higher risk of certain tumors such as lymphomas and skin cancers and than the general and dialysis populations. We retrospectively studied the prevalence of tumors in adult renal transplant recipients in four Tunisian centers of transplantation in Tunis, Monsatir and Sfax from January 1986 to January 2005. The study included 36 patients; 19 men and 17 women with a mean age of 34.6 years (range from 18-54 years). The mean time since dialysis to transplantation was 43 months (6-131months). Maintenance therapy was based on calcineurin inhibitors (CNI) in 86 % of cases, on antimetabolites and corticosteroids in 100 % of cases. Anti-thymoglobulin was administered in a mean course of 12.4 days in 78 % of the patients. Acute rejection occurred in 25 cases and was treated with polyclonal or monoclonal antibodies on 40 % of cases. Incidence of cancer among our population was 7 % and occurred after a mean period of 54 months of transplantation (range from 4-160 months). Eighty three percent of the tumors were solid, and the rest were in the skin. Kaposi sarcoma formed 41.6 % and non-Hodgkin or Hodgkin lymphoma 27.7 % of the solid tumors, while spinocellular carcinoma formed 83% and basocellular carcinoma 17% of the skin tumors. Switching CNI to sirolimus in 8.3% cases was associated with a favorable outcome. Mortality was the outcome in 33.3% of the patients with cancer, while partial or complete regression of cancers was observed in 55.5% cases after decreasing the doses of the immunosuppressive medications. We conclude that post renal transplant cancer is mainly characterized by the predominance of Kaposi sarcoma favored by solar exposure and rigorously induced and maintained immunosuppression. Careful follow-up may results in early inter-vention and decrease mortality.

Seborrheic keratosis are one of the most common benign epidermal tumors encountered in clinical practice. Malignant transformation is exceptional. It may occur by the involvement of human papilloma virus. We report two cases of seborrheic keratosis in respectively 58 and 60-years-old women, which, on biopsy, revealed the presence of Bowen's disease for the former and Squamous cell carcinoma for the later.

To study of the association between thyroid carcinoma and Hashimoto's thyroiditis (HT).[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.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 (size10 mm).We did not find an increased incidence of thyroid cancer associated with this highly selected population of HT patients.

Diabetic nephropathy is a multifactorial diabetic complication whose long-term consequences involve chronic renal insufficiency and increased rate of cardiovascular death. Besides oxidative stress, and hemodynamic changes, glycosaminoglycans (GAGs) are an additional component implicated in the onset of glomerular abnormalities. GAG replacement therapy was envisaged in the nineties for the treatment of diabetic nephropathy and sulodexide is the most extensively investigated GAG to reduce albuminuria in diabetic patients.In this study we have evaluated the effect of a long-term course of oral sulodexide at a moderate dosage in the treatment of patients affected by diabetic nephropathy. Thirty patients with type 1 and 2 diabetes mellitus (DM) have been treated with 50 mg/ daily oral sulodexide for 12 months while thirty matched diabetic patients constituted the control group. All the patients attended monthly visits and controls of biochemical and metabolic parameters.At 12 months albuminuria was greatly reduced in patients treated with sulodexide and increased in the control group (260% and +29% vs baseline, respectively; p = 0.0001). The drug appeared active in both type 1 and type 2 diabetes and in both micro- and macroalbuminuric patients. No change in metabolic control and no systemic side effects were reported.In our diabetic patients sulodexide therapy has been proven to greatly reduce albuminuria, and to have the potential to delay progression from incipient to overt nephropathy.

Elimination of syringes and needles is regulated in hospitals. However, the regulations remain unknown of diabetic patients who do not eliminate correctly their syringes of insulin. We propose to analyze the present situation concerning the management of used syringes of insulin by diabetic patients. This study was conducted in a clinic for diabetics and it involved 100 diabetic patients treated with insulin. The results of this study shaved an insufficiency in the management of syringes of insulin by diabetic patients. Thus, education and a conscionsness-raising of diabetic patients on management and correct use of syringes are necessary.

Male breast cancer is rare compared to its female counterpart representing less than 1% of cancer in men. The objective of our retrospective study is to report the epidemiologic and clinical profile and to analyse the therapeutic results and prognostic factors in a Tunisian population collected during a period of 20 years at a single institution. We collected from 1979 to 1999, all the histological confirmed male breast cancers treated at our institution. We analyse the following data: age, clinical presentation and features, therapeutic protocol, results and prognostic factors. Survival was done with the Kaplan-Meier method and comparison with the log-rank test. 123 cases of male breast carcinoma were collected with a median age of 65 years. Most patients (62.2%) have an advanced T4 disease with bilateral lesions in 4 cases. Infiltrating ductal carcinoma represent 91% of all tumours. 85% of tumours expressed hormonal receptor. The treatment consisted in a radical mastectomy in 93 cases (84%) followed by radiotherapy, chemotherapy and in many cases by hormonotherapy. After a median follow up of 26 month, 22 patients presented loco regional recurrence and 41 metastases. Estimated 5-year survival rate was 62%. The presence of metastasis, nodal involvement, advanced disease, and grade affected survival. Male breast cancer represent at our institution 1 % of the male cancers treated comparable to the literature data. T4 tumours represent a higher rate, the treatment approach is the standard applicable in breast cancer; prognostic factors are the classical one like breast cancer in women.

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.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.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).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.

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.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.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).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.

Clear cell carcinoma is the most frequent cancer of the kidney (60-80% of cases). This tumour has a great propensity to metastasis. Metastasis lesions appear 15 to 20 years after nephrectomy and differential diagnosis with can be difficult to establish. We report an exceptional case of renal cell carcinoma metastasis to the tongue in a 63-years-old male patient who had a nephrectomy 20 years previously. To our knowledge, this is the second case reported in the literature.

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%.

The sarcoma of the penis is a very rare tumor more exceptional is the Leiomyosarcoma of the penis for which the diagnosis required an immunohistochemical study. The prognosis for this tumor is poor. We report a case, which arise to a 53 year-old-man in this instance we did a review of the medical literature.

To report the profile of histologic cervical nodes involvement associated with mobile tongue squamous cell carcinoma.Our retrospective study concerned patients treated from 1978 to 1998 by cervical neck dissection for mobile tongue carcinoma.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.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.

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.

Chronic renal failure and periodic hemodialysis, by the physical reach and the therapeutic imperatives that they mislead disrupt by several ways the universe of the patient. This one is confronted to changes, or even to aggressions that undergo his body, his domestic and socio-professional life, which is accepted in general with difficulty. Indeed, our survey that concerned 109 patients on chronic hemodialysis shows that the minor psychiatric pathology is frequent and can represent a source of problems as well for the patients that for the medical and nursing staff. Besides the analysis of minor psychiatric specificities revealed by a known measure instrument (the GHQ), this work insists on the importance to take account of this aspects with the aim to enhance management and holistic care of these patients.

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.

To report on the epidemiological and therapeutic features of a series of Tunisian patients treated for primitive sinonasal lymphoma.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).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.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.

Renal involvement in amyloidosis leads to chronic renal failure. Prognosis is poor. Although amyloid deposits are frequent in adrenal glands, symptomatic adrenal dysfunction is uncommon. We report the case of a 63-year-old man with chronic renal failure (serum creatinine: 202 micromol/L) subsequent to amyloidosis who was referred to our unit for vomiting, dehydration despite a persistent nephrotic syndrome, acidosis, hyponatremia (121 mmol/l) and hyperkaliemia (7.1 mmol/l). A synacthen test was performed and disclosed adrenal insufficiency. Despite the initiation of substitution therapy, the patient died one month later from Addisonian crisis. Features of adrenal insufficiency may be masked by those of chronic renal failure, emphasizing the importance of adrenal explorations in patients with chronic renal failure due to amyloidosis.

Thirty Tunisian patients with a voluminous multinodular goiter with cold nodules and inhabiting a region of mild iodine deficiency, have been studied. The 131 I fixation by the thyroid, three hours after ingestion was significatively higher than in normal population. Fourty six per cent of the patients have stable iodine urine contents less or equal to 0.39 mumol/L. Three serum concentrations were paradoxically abnormal: thyrotropin (TSH), thyroglobulin (TG) and gammaglobulin concentrations. Fourty seven per cent of the serum thyrotropin (TSH) levels were less than the normal values though the serum total triiodotyronine (TT3), tetraiodotyronine (TT4), free triiodotyronine (FT3), free tetraiodotyronine (FT4), antithyroglobulin antibodies, total protein, triglycerides and cholesterol concentrations were normal. Serum thyroglobulin (TG) rates were elevated, ranged from 2 to 10,180 ng/ml and twenty five per cent of our patients showed levels greater than 500 ng/ml. The gammaglobulin levels were greater than normal in sixty eight per cent of our patients though only 10% of our patients manifest antithyroglobulin antibodies.

Ochratoxin A (OTA) is a mycotoxin which has been implicated in Balkan Endemic Nephropathy (BEN), a disease characterized by tubulonephritis and may be involved in the high incidence of urinary tract tumors associated to BEN. The prevalence of human ochratoxicosis is being determined in Tunisia. 100% of people suffering from chronic interstitial nephropathy of unknown etiology were ochratoxin A positive. These nephropathies are similar to Balkan Endemic Nephropathy. We prove an OTA genotoxic effects in patient suffering from this kind of nephropathy. OTA-DNA adducts formation has been detected in DNA of kidney tissues (biopsy). DNA adducts which are covalent complex between OTA and DNA base (Guanine), constitute first steps of the carcinogenesis process.

Twelve renal abscesses were treated with percutaneous aspiration (6 patients), percutaneous drainage (3 patients) or antibiotics alone (3 patients). The diagnosis was established based on computed tomography-guided aspiration in 9 cases and on radiographic findings and follow-up in the remaining 3. A bacterium was isolated in 2 out of 9 blood cultures, 2 out of 11 urine cultures and in all cultures of pus obtained by percutaneous aspiration. All patients had a good outcome. Our findings confirm the efficacy of percutaneous aspiration in the treatment of renal abscesses. Percutaneous drainage should only be considered when the abscess is very large or aspiration has failed.

Prospective study of 280 diabetic adults and 100 control show an association of limited joint mobility (LJM) with Dupuytren's contracture (DC) in 37 diabetic and no one of control case. In 80 diabetic with LJM, DC is found in 46.25 p. cent against 21 p. cent in 200 diabetic without LJM (p less than 0.00003). LJM and DC are significantly related to diabetic retinopathy and neuropathy. Their coexistence in diabetic patients, reported by other authors may be related to diffuse alteration of diabetic connective tissue.

The incidence of suicide among cancer patients has been examined in several previous epidemiological studies, which have suggested an increased risk especially in the period following diagnosis. The role of factors which may modulate the risk, such as individual patient characteristics or that of cancer (site, prognosis or type of treatment), have not been systematically studied and available results are often contradictory. In Geneva, the existence of a tumor registry, which follows patients continuously until the cause of death is known, has enabled us to conduct a cohort study on all incident cases of cancer registered for the years 1970 to 1983. The risk of suicide (SMR) was found to be significantly elevated for both sexes in the first two years following diagnosis. Thereafter, the risk diminished, and for the entire 15 year period considered, the risk remained significantly elevated only for women. The effect of variables which may have modulated the risk was examined through a logistic regression analysis comparing cases and controls selected from the same cohort. The risk was significantly lower for married patients. No difference between sex was observed, but the risk of suicide appeared to be increased in the elderly, as well as in foreigners, and to be reduced in upper socio-economic classes. Risk could be higher with neoplasms of the digestive tract and lower with those of the breast. Because incidence of suicide is relatively low, studies may lack statistical power to detect a moderately increased risk. Nonetheless, these results confirm part of previous results and contribute further to the study of this problem.

Based on two pretreatment evaluations, doubling time (DT) was calculated in 75 cases of invasive breast cancer (BC). The cases studied were more or less equally distributed between three DT groups: fast-growing tumors (DT less than 90 days), intermediate cases (DT between 90 and 180 days), and slow-growing tumors (DT greater than 180 days. A correlation was found to exist between DT and patient age and, to an even greater extent, between DT and pathologic prognostic indicators such as histologic grading and nuclear grade. Inflammatory symptoms were not associated with DT, but were closely related to the size of the tumor and regional lymph node involvement. The date of detection of distant metastases depended heavily on the DT of the BC:BC with shorter DT = earlier metastatic spread. The presence of inflammatory signs was also decisive: within each DT category, inflammatory BC metastases were both more frequent and precocious.