Therapeutic results of laryngeal preservation: a retrospective study.

AIM: The objective of this study is to report the therapeutic results of the preservation strategy in locally advanced laryngeal cancers. PATIENTS AND METHODS: Between January 2008 and December 2015, 24 patients with locoregional advanced non-metastatic laryngeal cancer (T2-4/N0-2) were collected retrospectively. Different therapeutic sequences were used: either induction chemotherapy followed by concurrent chemoradiotherapy or induction chemotherapy followed by radiotherapy or concurrent chemoradiotherapy or radiotherapy alone. RESULTS: The objective response rate was 85.7%. Overall survival rates at 1 year, 3 years and 5 years were 91.3%, 80.2% and 53.5%, respectively. Administration of induction chemotherapy did not improve overall survival. The 1-year overall survival was 83.3% in the induction chemotherapy group vs 94.1% for those who did not received induction chemotherapy (p = 0.7). CONCLUSION: Our study showed the feasibility of this preservation strategy in clinical practice, with acceptable term toxicity.

Buschke - Lowenstein anal tumor: an ambiguous entity.

The Buschke - Lowenstein tumor is a rare sexually transmitted disease. Its location at the anal margin is also very rare. The most incriminated risk factor is human papillomavirus infection. Its clinical form may be confusing with other tumor and infectious lesions. Histologically, it is characterized by a well-differentiated malpighian proliferation. It represents local aggressive behavior. The treatment of reference remains the surgery with healthy margins of excision. Other treatments have been tested, but their effectiveness remains uncertain. We report here a new case of anal margin Buschke - Lowenstein tumor with a review of the literature.

Hemophagocytic lymphohistiocytosis associated with an IgG Cold agglutinin.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease eventually caused or reactivated by a viral infection, which can also lead to the production of cold agglutinins (CA). The nature of these autoantibodies is usually an IgM, less frequently an IgA or IgG, they agglutinate red blood cells at low temperatures. They can interfere with hematological parameters causing interpretation difficulties. We report a case of a 4-year-old boy who developed an IgG CA during recurrent HLH reactivated by EBV infection. The purpose of this observation is to underline HLH criteria and to analyze CA interference as well as its biological and clinical characteristics.

Gastric signet-ring cell carcinoma with hypersecretion of ß-Human chorionic gonadotropin and review of the literature.

ß-Human chorionic gonadotropin (ß-HCG) is an embryonic protein secreted by the syncytiotrophoblast of the placenta. The determination of the plasma ß-HCG level is routinely used for the diagnosis and the follow-up of germ cell tumors. Some adenocarcinomas have been described as being rarely associated with ß-HCG hypersecretion. We report a case of gastric signet-ring cell carcinoma with ß-HCG hypersecretion and propose hypotheses to explain the pathogenesis of such hypersecretion.

TPF induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma: Long term results of a Tunisian series.

PURPOSE: We represent in this study the long term results of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by concurrent chemoradiotherapy in Tunisian patients with locally advanced nasopharyngeal carcinoma. The objective of our study is to analyse the efficacy as well as the toxicity of this therapeutic protocol. PATIENTS AND METHODS: Between January 2004 and December 2008, 32 patients with locoregional advanced non metastatic disease (T2b or above and/or N1 or above AJCC 2002) were treated in our institution by three cycles of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy every 21 days followed by concurrent chemoradiotherapy. Conventional radiotherapy was delivered using a cobalt 60 machine during 7 weeks with weekly cisplatin (40mg/m2). RESULTS: Twenty-nine patients (90%) had presented an objective clinical response in lymph nodes after neoadjuvant chemotherapy, with a complete response in 28%. Acute toxicity of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy was dominated by vomiting (59%), asthenia (40.6%), diarrhea (34.4%) and febrile neutropenia (15.6%). The complete response rate after the end of treatment was around 80%. The 5 years overall survival and disease-free survival were respectively 68.2% and 67.5%. CONCLUSION: Our results, in this field of study, are encouraging with acceptable toxicity despite the lack of intensity-modulated radiotherapy technique in our institution during the period of study.

A long survival of a patient with brain metastasis of unknown site of the primary tumor.

Eighty percent of brain metastases (BM) are diagnosed in patients with known primary site of cancer. BM of unknown primary represents a difficult diagnosis. In up to 15% of patients with BM, the site of the primary tumor will not be detected despite investigations. The prognosis of this entity is very poor. We report here a case of a long survival of a patient with brain metastasis of unknown primary. The conclusion that can be drawn is that within BM of unknown primary exist patients with a very good prognosis that must be collected and published in order to base recommendations.

A randomized trial of induction docetaxel-cisplatin-5FU followed by concomitant cisplatin-RT versus concomitant cisplatin-RT in nasopharyngeal carcinoma (GORTEC 2006-02).

Background: Concomitant chemotherapy (CT)-radiotherapy (RT) is a standard of care in locally advanced nasopharyngeal carcinoma (NPC) and a role for induction CT is not established. Methods: Patients with locally advanced NPC, WHO type 2 or 3, were randomized to induction TPF plus concomitant cisplatin-RT or concomitant cisplatin-RT alone. The TPF regimen consisted of three cycles of Docetaxel 75 mg/m2 day 1; cisplatin 75 mg/m2 day 1; 5FU 750 mg/m2/day days 1-5. RT consisted of 70 Gy in 7 weeks plus concomitant cisplatin 40 mg/m2 weekly. Results: A total of 83 patients were included in the study. Demographics and tumour characteristics were well balanced between both arms. Most of the patients (95%) in the TPF arm received three cycles of induction CT. The rate of grade 3-4 toxicity and the compliance (NCI-CTCAE v3) during cisplatin-RT were not different between both arms. With a median follow-up of 43.1 months, the 3-year PFS rate was 73.9% in the TPF arm versus 57.2% in the reference arm [hazard ratio (HR) = 0.44; 95% confidence interval (CI): 0.20-0.97, P = 0.042]. Similarly the 3 years overall survival rate was 86.3% in the TPF arm versus 68.9% in the reference arm (HR = 0.40; 95% CI: 0.15-1.04, P = 0.05). Conclusion: In conclusion, several important aspects can be emphasized: the compliance to induction TPF was good and TPF did not compromise the tolerance of the concomitant RT-cisplatin phase. The improved PFS and overall survival rates needs to be confirmed by further trials.

Fibrinogen Mahdia: A congenitally abnormal fibrinogen characterized by defective fibrin polymerization.

INTRODUCTION: Congenital dysfibrinogenemia is a rare qualitative fibrinogen deficiency. Molecular defects that result in dysfibrinogenemia are usually caused by mutations which affect fibrinopeptide release, fibrin polymerization, fibrin cross-linking or fibrinolysis. AIM: Here, we investigated the genetic basis of hypodysfibrinogenemia in two Tunisian siblings with major bleeding. METHODS: Coagulation-related tests were performed on the patients and their family members. Functional analysis was performed in plasma fibrinogen to characterize fibrin polymerization. The sequences of fibrinogen genes were amplified and analysed by sequencing. RESULTS: Coagulation studies revealed a reduced functional and a borderline low antigenic fibrinogen plasma levels with prolonged thrombin and activated partial thromboplastin times. The fibrinogen is also characterized by a markedly impaired polymerization and could incorporate into fibrin fibres to a smaller extent (22%). Mutational screening disclosed a heterozygous single nucleotide deletion (G) at c.1025, resulting in a frameshift mutation (AαGly323GlufsX79) that is predicted to delete a part of the αC-domain containing some of the FXIII cross-linking sites. Both the normal and the aberrant Aα-chain (approximately 43 kDa) were detected by electrophoretic analysis in the patients. CONCLUSION: The new dysfunctional fibrinogen, Mahdia variant, describes its impact on fibrin assembly after the loss of the αC domains which are involved in the lateral aggregation of protofibrils. The study confirms that the truncated Aα-chain could be incorporated into mature fibrinogen molecules.

[Neuroendocrine carcinoma of the bladder: A single centre retrospective study]. / Carcinome neuroendocrine de la vessie: étude rétrospective monocentrique.

PURPOSE: Neuroendocrine carcinoma of the bladder is a rare tumour representing 0.5 to 1% of bladder tumours. It is a specific histological entity characterized by rapid metastatic dissemination and poor prognosis. The aim of this study was to describe the epidemiological, clinical, therapeutic modalities and the evolutive aspects of patients receiving a treatment for bladder neuroendocrine carcinoma. PATIENTS AND METHODS: Between January 2004 and January 2014, seven patients received a treatment for a neuroendocrine carcinoma of the bladder, at the department of oncology, Habib-Bourguiba Hospital, in Sfax, Tunisia. RESULTS: The median age was 58 years. All patients were male. Neuroendocrine carcinoma was pure in four cases and associated with urothelial carcinoma in the other three cases. Two patients were diagnosed at a metastatic stage. A cystectomy was performed in two cases. One patient received a chemotherapy and radiotherapy. The other four patients received chemotherapy alone. A single case of complete remission was observed. Median survival was 15 months (5-30 months). One patient is still alive 30 months after diagnosis. CONCLUSION: The management of neuroendocrine carcinoma of the bladder is not standardized and requires a multidisciplinary consultation.

[Autoimmune hemolytic anemia in children]. / Anémie hémolytique auto-immune de l'enfant.

Autoimmune hemolytic anemia is a rare condition in children which differs from the adult form. It is defined by immune-mediated destruction of red blood cells caused by autoantibodies. Characteristics of the autoantibodies are responsible for the various clinical entities. Classifications of autoimmune hemolytic anemia include warm autoimmune hemolytic anemia, cold autoimmune hemolytic anemia, and paroxysmal cold hemoglobinuria. For each classification, this review discusses the epidemiology, etiology, clinical presentation, laboratory evaluation, and treatment options.

[Primary neuroendocrine tumors of the breast: a retrospective study of 21 cases and literature review]. / Tumeurs neuroendocrines primitives du sein: étude rétrospective de 21 cas et revue de la littérature.

PURPOSE: The aim of the present study was to discuss the epidemiology, clinical and pathologic features, treatment, and prognosis of primary neuroendocrine carcinomas of the breast. PATIENTS AND METHODS: We report 21 cases diagnosed over a period of 12 years (1995-2011) at the university hospital of Sfax. A review of the clinical data with pathology and immunohistochemistry study was carried out for all the cases. RESULTS: The average age was 62 years (34-86 years). At the time of the diagnosis, tumours were classified T1 and T2 (16 cases), N1 (11 cases) and M1 in two cases. The histological examination has shown 13 cases of solid neuroendocrine carcinoma, six cases of large cell type and two cases of atypical carcinoid. Grade I and II SBR were found in 18 cases. Eighty-one percent of the tumours were reactive for synaptophysin; all tumours were positive for chromogranin. Thirteen (61.9%) tumours were estrogen receptor-positive and 12 (57.5%) progesterone receptor-positive. Nineteen (90.5%) tumours were negative for HER2/neu. Overall five-year survival was 72.7%. All patients had surgical treatment with modified radical mastectomy in 13 cases. Adjuvant treatment was indicated according to histopronostic elements. CONCLUSION: For primary neuroendocrine carcinoma of the breast, multivariate analysis identified three predictive factors for mortality: disease stage, histological grade and lymph node involvement.

Association between clinical expression and molecular heterogeneity in ß-thalassemia Tunisian patients.

Beta-thalassemia is the most frequent hereditary blood disorder in Tunisia because of its geographic localization and history. This pathology is characterized by a complex multisystem process with genetic and biochemical interactions. The aim of this work was to establish phenotype/genotype association through studying the distribution and the relationship between ß-thalassemia and α-thalassemia mutations and three polymorphic markers: the C → T polymorphism at -158 of the Gγ gene, the RFLP haplotype and the repeated sequence (AT)xTy in the ß globin silencer, in two groups of ß-thalassemia major and ß-thalassemia intermedia (TI) patients. Statistical analysis has shown that moderate expression seen in TI patients was significantly associated to ß(+) -87 (C → G), -30 (T → A) and IVSI-6 (T → C) mutations, haplotypes VIII, IX and Nb and to XmnI polymorphism. The regression analysis of combined genotypes (mutation/XmnI/RFLP haplotype) revealed that they contribute to justify 17.1 % of clinical expression diversity (p < 0.05). Among the studied genotypes the XmnI polymorphism seems to be the most determinant modulating factor, followed by the ß-thalassemia mutation and RFLP haplotype. Our findings highlight the heterogeneity of molecular background of ß-thalassemia that would be responsible of clinical variability.

Glucose-6-phosphate dehydrogenase deficiency in Tunisia: molecular data and phenotype-genotype association.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. In this study, we aimed to perform a molecular investigation of G6PD deficiency in Tunisia and to associate clinical manifestations and the degree of deficiency with the genotype. A total of 161 Tunisian subjects of both sexes were screened by spectrophotometric assay for enzyme activity. Out of these, 54 unrelated subjects were selected for screening of the most frequent mutations in Tunisia by PCR/RFLP, followed by size-based separation of double-stranded fragments under non-denaturing conditions on a denaturing high performance liquid chromatography system. Of the 56 altered chromosomes examined, 75 % had the GdA(-) mutation, 14.28 % showed the GdB(-) mutation and no mutations were identified in 10.72 % of cases. Hemizygous males with GdA(-) mutation were mostly of class III, while those with GdB(-) mutation were mainly of class II. The principal clinical manifestation encountered was favism. Acute hemolytic crises induced by drugs or infections and neonatal jaundice were also noted. Less severe clinical features such as low back pain were present in heterozygous females and in one homozygous female. Asymptomatic individuals were in majority heterozygote females and strangely one hemizygous male. The spectrum of mutations seems to be homogeneous and similar to that of Mediterranean countries; nevertheless 10.72 % of cases remain with undetermined mutation thus suggesting a potential heterogeneity of the deficiency at the molecular level. On the other hand, we note a better association of the molecular defects with the severity of the deficiency than with clinical manifestations.

[Ovarian metastasis from bronchial carcinoma]. / Métastase ovarienne d'un carcinome bronchique.

INTRODUCTION: The ovary, being a richly vascular organ, may receive metastases from numerous tissues, particularly of gynecologic origin. Extragenital cancers are dominated by gastro-intestinal and breast tumors. The lung is exceptionally described as a primary site of ovarian metastasis. CASE REPORT: We report a 28-year-old woman who was found to have a right perihilar opacity. The diagnosis of small cell bronchial carcinoma was made by bronchial biopsy. A right-sided uterine mass was also identified. This was resected and histopathology identified it as an ovarian metastasis from the pulmonary tumor. CONCLUSION: We report, through this case, and present a review of the literature on ovarian metastasis originating from bronchopulmonary neoplasms.

[Juvenile nasopharyngeal carcinoma: anatomoclinic, biologic, therapeutic and evolutive aspects]. / Les cancers du cavum juvéniles: aspects anatomocliniques, biologiques, thérapeutiques et évolutifs.

Nasopharyngeal carcinoma (NPC) represents one of the most frequent epithelial tumours of the child in intermediate risk regions. In the Maghreb, it represents the first cancer of teenagers of 15-20 years old. The Epstein Barr virus (EBV) is the most important etiologic factor. Its role in the pathogeneses of NPC has been confirmed by several studies. Young NPCs are characterized by a low rate of EBV antibodies and a high level of LMP1 cell expression than in adult's NPC. The undifferentiated carcinoma nasopharyngeal type (UCNT) represents the most frequent histological type. Immunohistochemical analyses of North Africa early onset NPC is characterized by a weak expression of bcl-2 and p53 and a strong expression of LMP1 and c-kit what makes them different from the adult's NPC. Clinically, cervical node involvement is constantly present. Juvenile NPC is characterized by a very important locoregional extension as well as a high rate of distant metastases. More than 15% of patients had metastases at diagnosis. Radiotherapy is still the standard therapy of NPC. Only some retrospectives studies have been published to determine the benefit, the type and the timing of the chemotherapy in the treatment of juvenile NPC. Metastatic relapses constitute the main cause of death at these young patients. An improvement of the prognosis can be waited with concomitant chemotherapy and intensity modulated radiotherapy. However, randomized multi institutional studies are necessary to standardize the treatment of the NPC in childhood.

[North African and Southeast Asian nasopharyngeal carcinomas: between the resemblance and the dissemblance]. / Le carcinome nasopharyngé en Afrique du Nord et dans le Sud-Est asiatique: entre similitude et différence.

Nasopharyngeal carcinoma (NPC) is an unusual head and neck cancer because of its unequal geographical distribution and its consistent association with the Epstein-Barr virus (EBV). This malignant tumor poses a serious public health problem in many countries, especially in Southeast Asia and North Africa where the recorded incidence are highest. During the past decade, a growing number of studies were undertaken to define the molecular basis of NPC. However, the analysis of several clinical and biological parameters of North African and Southeast Asian NPCs has shown notable differences, suggesting that they could result from a distinct combination of etiological factors. One intriguing characteristic of North African NPC, concerns its bimodal age distribution with a secondary peak of incidence in the range of 15-25 years, not observed in Asian NPC. In this juvenile form of NPC, immuno-histochemistry assay has shown that the two key proteins controlling the apoptotic-survival balance p53 and Bcl-2 are less frequently expressed whereas the transmembrane tyrosine-kinase receptor c-kit and the main EBV oncoprotein LMP1 were more abundant. In addition, the EBV serological alterations are less informative for the diagnosis of the juvenile compared to the adult form. In addition, most North African NPCs contain EBV strains with genetic polymorphisms distinct from those described in the Southeast Asia series (predominance of F, D, H1-H2, XhoI+ and f, C, H, XhoI- respectively). In contrast, studies relating on tumor chromosomal alterations or aberrant promoter methylation result in data very similar to those obtained from the Southeast Asia series, supporting the concept of a common molecular basis for all NPC regardless of patient geographic origin.

[Tunisian experience in the treatment of aggressive non Hodgkin's lymphoma in adults: about 337 patients]. / Expérience tunisienne dans la prise en charge des lymphomes agressifs de l'adulte: à propos de 337 patients.

From January 1997 to December 2005, 337 patients with aggressive non Hodgkin's lymphoma were treated with one of the two successive multicentric non randomized protocols established in Tunisia. The mean age was 53 years. Most patients had diffuse large cell lymphoma with B phenotype in 86% and T in 14%. The performance status was 2 or 3 in 34% of cases. The LDH were elevated in 74% of cases. Advanced disease (III or IV stage) was noted in 59% of cases and 10% had a tumoral mass greater than 10 cm. According to the international prognostic index (IPI) adjusted to age, we distinguish four groups: group 1 (0 factor and age < 70 years), group 2 (1-3 factors and age < or = 60 years), group 3 (1-3 factors and age between 61 and 70 years) and group 4 (1-3 factors and age > 70 years). The patients of group 1 (N = 47) received 3 courses of CHOP regimen followed by irradiation. The patients of group 2 (N = 160) received 4 courses of ACVBP regimen (+ rituximab for 21 patients) followed by consolidation (N = 92) or peripheral blood progenitor cell transplantation (N = 20). The patients of group 3 (N = 61) received 8 courses of CHOP regimen (+ rituximab for 20 patients). The patients of group 4 (N = 69) received 6 courses of mini-CEOP regimen (N = 48) or 6 courses CVP regimen (N = 21). The 4-year overall survival was 56% and the 4-year event free survival was 49%.

[Pediatric nasopharyngeal carcinoma: Anatomoclinic aspects, therapeutic results and evolutive particularities]. / Le cancer du cavum de l'enfant et l'adulte jeune : aspects anatomocliniques, thérapeutiques et particularités évolutives.

PURPOSE: We retrospectively analyzed anatomoclinic, therapeutic and evolutive particularities of 74 young patients (< or =20 years) with nasopharyngeal carcinoma treated between 1993 and 2005. PATIENTS AND METHODS: Initial work-up included a fiberoptic nasofibroscopy with biopsy, tomodensitometry and/or MRI of nasopharynx and neck, chest X-ray, abdominal ultrasonography and bone scan. Patients were treated with either primary chemotherapy (epirubicin and cisplatin) followed by radiotherapy or concomitant radiochemotherapy (five fluorouracil and cisplatin). Radiotherapy was delivered to a total dose of 70 to 75 Gy to nasopharynx and involved cervical lymph nodes and 50 Gy to the remainder cervical areas. RESULTS: The median age was 16 years. Sixty-three percent of patients had undifferentiated tumors. Sixty-six percent had locally advanced tumor. With a median follow-up of 107 months, one patient presented a local relapse, 24 patients developed distant metastases with a median delay of 7 months. The 5 years overall survival and disease-free survival were 66 and 65 %. Late complications were dominated by dry mouth and endocrine disorders. COMMENTS: Pediatric nasopharyngeal carcinoma is characterized by an early metastatic diffusion. Local control is excellent but with severe late toxicities. New techniques of radiotherapy and new molecules of chemotherapy could improve these results.

Small cell osteosarcoma: a case report.

INTRODUCTION: Small cell osteosarcoma (SCO) is a rare bone tumour representing 1.3% of all osteosarcomas. This rare variety of osteosarcoma tends to arise in the metaphysis of long bones and may extend secondary to epiphysis. By histopathology, the tumour is composed of small round cells with a variable degree of osteoid production. We report a new case of SCO in the distal femur with epiphyseal involvement. We also present the clinical, radiologic and therapeutic features of SCO with particular emphasis on the pathologic features that allow differentiation of this neoplasm from other small round cell tumours. OBSERVATION: A 14-year-old girl presented with a 6-month history of a painful tumefaction of the left knee with motor deficit. Imaging analysis of the knee demonstrated a lytic lesion of the metaphysis in addition to epiphysis of the distal femur with cortical destruction and invasion of soft tissues. Histological examination of a biopsy specimen showed sheets of neoplastic small round cells simulating Ewing's sarcoma. Osteoid was focally present. A diagnosis of SCO was made. The patient received 2 cycles of adjuvant chemotherapy with ifosfamide, adriamycin and cisplatin. MRI showed no change in tumour size. An en bloc, wide-margin resection of the lesion was performed. Histological examination showed a viable tumour with few necrotic foci. The patient received adjuvant chemotherapy with Holoxan and VP16. The clinical response was favourable. CONCLUSION: SCO is a rare clinical entity with a high grade of malignancy that must be distinguished from other round cell tumours, particularly Ewing's sarcoma, in order to optimise treatment protocols.