Search

Unexplained deep vein thrombosis may justify screening for antineutrophil cytoplasmic antibody‐associated vasculitis as it can be an unusual presentation of this disease.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits is a new disorder with undefined treatment modalities. We propose cyclophosphamide‐bortezomib‐dexamethasone and autologous stem cell transplantation as a therapeutic protocol.

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 (

Background and Aims Peritoneal Dialysis (PD) is now often being initiated in older patients. The benefits of this modality of dialysis have been well demonstrated in the literature. The aim of our study was to analyse the epidemiological and clinical profile of the elderly patients and to determine predictive factors of mortality Method It was a retrospective study including 51 case defined as patients ≥65-year-old, treated by PD in the Internal Medicine Department of the Charles Nicolle hospital during the period between 1986 and 2020. Results Fifty one patients were enrolled in the study. Their mean age was 71,6 ± 5,4 years [65 - 86]. There were 32 men (62, 7%) and 19 women (37,2%) . The method of initiation was the PD in 53, 84%. Diabetic and vascular nephropathy was the first cause of End-Stage Renal Disease in 56% and 19,6%. The mean Charlson score was 5,5 ± 1,4 [3-9]. The mean age when using PD was 70.8 ± 6 years [54-86]. Autonomous and active patients were detected in 29.4%. Diabetes mellitus, hypertension and coronary artery disease was observed in 58,8%, 29,4% and 15.7% of patients. In our study, 82.35% started on automated PD (APD) and 17,6% on continuous ambulatory PD (CAPD). The rate of mortality was 53%. Switching modality from PD to hemodialysis occurred in 29,4% of cases. A univariate logistic regression identified a coronary artery disease as significantly associated with increased mortality (HR=2,1 [1-2,1, IC 95%](p=0.035)). Conclusion Elderly patients on dialysis face many issues but can have continued success with PD when they have adequate care and support. The control of the morbidities such as coronary artery disease is important to decrease the rate of mortality in patients using this modality of dialysis.

Background and Aims Acute kidney injury (AKI) is common in the elderly due to physiologic renal aging and underlying pathologies. Few studies focused on AKI in Tunisian elderly. The aim of our study was to highlight the epidemiological, clinical, etiological, therapeutic, and progressive characteristics of AKI in elderly. Method We conducted a descriptive retrospective study of AKI in patients admitted to our department over a period of 04 years from 01/01/2014 to 31/12/2017. Results We collected 40 patients including 25 women and 15 men with a sex ratio of 1.66. The mean age was 74 [65-87] years. We noted the presence of pre-existing chronic kidney disease in 58% of cases, diabetes in 50% of cases and hypertension in 73% of cases. Polypharmacy was found in 40% of cases. AKI was symptomatic in 80% of cases and found on a routine check-up in 20% of cases. Mean creatinine was 612+/-334 µmol/l. AKI was pre-renal in 37% and parenchymal in 63% of cases. Iatrogenic origin was found in 33% of cases. Renal biopsy was performed for diagnostic purposes in 6 cases. Haemodialysis was necessary in 50% of cases. Etiopathogenic treatment was initiated in 73% of cases. Intra-hospital mortality was 10%, recovery of renal function (RF) was partial in 40 % of cases and total in 20 % of cases. Follow-up time was 16 +/- 23.2 months. And at the last news, recovery of renal function (RF) was partial in 7 cases and total in 10 cases, 6 patients kept a chronic renal failure (CRF), among them 3 cases had and end-stage of CRF. Conclusion AKI is a frequent pathology in the elderly and its severity is linked to mortality and the transition to chronicity. Iatrogenic causes are frequent and preventable in this population, hence the major interest of prevention.

Background and Aims The B cells have a central role in the pathogenesis of several renal pathologies. Rituximab, a monoclonal antibody directed against the CD20 receptor expressed on the surface of B cells is an interesting alternative to conventional treatments of kidney pathologies. Method We conducted a descriptive retrospective study of the use of rituximab in nephrology patients. Results We collected 25 patients including 12 women and 13 men. The mean age was 33,5 [16-55] years. The rituximab was indicated for an extramembranous glomerulopathy in 6 patients, a focal segmental glomerulosclerosis in 4 patients, a minimal change disease in 4 patients, a lupus nephritis in 5 patients, and a granulomatosis with polyangiitis in 2 patients. Four kidney transplant patient received rituximab for the treatment of antibody mediated rejection in 3 cases and large cell lymphoma in 1 case. The average time between the diagnosis of the renal disease and starting treatment with rituximab was of 76 +/- 46,5 months. And it was of 16 [ 0,7 ; 59,8] months after transplantation in kidney transplant recipients. Side effects have been observed in 11 cases (44%). A favorable response has been obtained in 10 cases (40 %), within an average of 2,27 months, with at least one relapse in 4 cases. The follow-up time was 36,33 +/- 31,67 months. Conclusion Rituximab has been shown to be helpful in several cases of kidney disease. It may reduce the need for maintenance immunosuppression and help in some cases that are refractory to other therapies.

Background Karyomegalic interstitial nephritis (KIN) is a rare disease entity first described by Burry in 1974. The term KIN was introduced by Mihatsch et al. in 1979. KIN is characterized by chronic tubulointerstitial nephritis associated with enlarged tubular epithelial cell nuclei, which leads to a progressive decline of renal function. The prevalence of this disease is less than 1% of all biopsies, and its pathogenesis is unclear. KIN results from mutations in FAN1 (FANCD2/FANCI-Associated Nuclease 1), a gene involved in the DNA damage response pathway, particularly in the kidney. In this study, we report two Tunisian consanguineous families with KIN caused by mutations in the FAN1 gene. Methods Direct sequencing of the coding regions and flanking intronic sequences of the FAN1 gene was performed in three affected members. Three prediction programs (Polyphen-2 software, SIFT, and MutationTaster) were used to predict the functional effect of the detected variations. Results Two causative frameshift variants in the FAN1 gene were identified in each family: The previously described frameshift mutation c.2616delA (p.Asp873ThrfsTer17) and a novel mutation c.2603delT (p.Leu868ArgfsTer22) classified as "pathogenic" according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Conclusion To our best knowledge, this is the first Tunisian study involving familial cases of KIN with mutations in the FAN1 gene. We hypothesize that these findings can expand the mutational spectrum of KIN and provide valuable information on the genetic cause of KIN.

Background and Aims The increase in life expectancy has led to increasing numbers of elderly patients in all medical disciplines, particularly in nephrology. Idiopathic membranous nephropathy (IMN) is common in the elderly and can lead to significant morbidity and mortality because of the complication of nephrotic syndrome (NS) and immunosuppressive therapy. The aim of this study is to analyze the diagnostic, therapeutic and evolutionary approach of IMN in elderly patiets. Method We conducted a retrospective descriptive study in the nephrology department at Charles Nicolle hospital over a period of 44 years. All older patients (≥65 years) with histologically proven MN were included in this study. Data collected included demographic, clinical and biological parameters in each patient. Data were entered and analyzed using SPSS software. Results Twenty-eight patients were collected. The mean age was 67.03 years (65-78 years) with a male predominance (sex ratio: 2.3) and low socio-economic level in 82.5% of cases. Sixteen patients were smokers (57.14%), 5 ethyl patients (17.8%), diabetes was present in 3 patients (10.7%) and hypertension in 11 patients (39.28%). Two cases of neoplasm were present, namely one case of prostatic adenocarcinoma and one case of gallbladder adenocarcinoma, all were diagnosed and treated along one year and ten years respectively, before the diagnosis of MN. The circumstances of discovery were dominated by oedema in 27 cases (86.27%), hypertension in 11 cases (39.28%) and elevated creatinine level in 9 cases (32.14%). Deep venous thrombosis was the circumstance of discovery in one case. At the time of diagnosis, the clinico-biological picture was dominated by high systolic blood pressure in 21 cases (75%), anasarca in 7 cases (25%), proteinuria in all cases and hematuria in 20 cases (71.14%). Biology revealed nephrotic syndrome (NS) in all cases, hypercholesterolemia in 23 cases (82.14%), high serum creatinine in 14 cases (50%) with an average creatinine level of 127,95 µmol/l, anemia in 17 cases (60.7%) and anti-neutrophil cytoplasmic antibodies were positive in one case. MN was confirmed by a kidney biopsy in all cases. Symptomatic treatment was indicated in all patients. Immunosuppressive therapy was started early in 12 patients (40%) because of the severe NS and the deterioration of renal function. Eight patients (26.6%) received corticosteroids alone (group 1), three patients received corticosteroid with mycofenolate mofetil (group 2) and one patient received corticosteroid with ciclosporin (group3). Fourteen patients received only symptomatic treatment (group 4). We noted partial remission in group 3, however complete remission in 37.5%, 14.28% and 12.5% from respectively group 1, group 4 and group 2. The side effects of immunosuppressive therapy were infectious complication in 8 patients (28.5%), osteoporosis in 3 patients (10.7%) and Steroid diabetes in one case. The side effects of NS were thrombotic complication in 5 patients (17.85%). Two patients had presented coronary syndrome and two other patients had presented hepatitis C. Two cases of death were noted whose etiology was pulmonary infection in one patient and undeterminate etiology in the other case. Conclusion Treatment of IMN in older patients has unique challenges, reducing the need for renal replacement therapy. Most studies report that the elderly respond to therapy with rates comparable with younger patients but in the other hand elderly are more susceptible to side effects of immunosuppressive therapy.

Background and Aims The occurrence of renal involvement during the clinical course of systemic lupus erythematous (SLE) is generally considered to be the most important factor influencing the prognosis in terms of morbidity and mortality. The factors influencing prognosis in lupus nephritis (LN) are variable in literature. The aim of our study was to analyze the clinicopathological correlations, and risk factors associated with renal failure in male patients with LN. Method We retrospectively studied all male patients with kidney biopsy-proven lupus nephritis (LN) treated in our department during the period between 1979 and 2016. Looking for predictive factors related to renal prognosis, we analyzed clinical, biological and histological data by multivariate analysis using the comparison of the survival rates by the log-rank test. Results We collected 41 native renal biopsies showing LN. Patients were aged 32.17 years (17-65 years) at the time of diagnosis of LN. Diagnosis of SLE was made according to the criteria of the American College of Rheumatology. The most common clinical presentation was nephrotic syndrome (61%), and the most frequent pathological finding in sediment was proteinuria (85%). At the time of diagnosis, 17% of patients had hypertension and 39 % of patients had an eGFR under than 60 ml/min/1.73 m2. LN was of class I, II, III, IV and V in 7.5%, 12.5%, 27.5%, 47.5% and 41.5% of the cases, respectively. Fourteen patients developed end-stage renal failure. The presence of hematuria, renal failure at the time of diagnosis, nephrotic syndrome, low complement, proliferative glomerulonephritis (class IV), high activity index score of LN and thrombotic microangiopathy were significantly associated with poor renal prognosis with (p=0.0053), (p=0.0002), (p=0.0186), (p=0.0287), (p=0.0005), (p=0.058), (p=0.0117), respectively. Conclusion Renal failure at the time of diagnosis and active proliferative lesions should be diagnosed and treated as soon as possible because they influence the renal prognosis in lupus man.

Background and Aims Idiopathic membranous nephropathy (IMN) is increasingly seen in older patients but little is known about its treatment and outcomes at long term follow up. The objective of this work is to study the renal survival of IMN in elderly as well as prognostic factors. Method We conducted a retrospective descriptive study in the nephrology department at Charles Nicolle hospital over a period of 44 years. All older patients (≥65 years) with histologically proven MN were included in this study. Data collected included demographic, clinical and biological parameters in each patient. Data were entered and analyzed using SPSS software. Chi-squared test with a level of significance of 0.05 was used for the qualitative variables. Results Twenty-eight patients were collected. The mean age was 67.03 years (65-78 years) with a male predominance (sex ratio: 2.3) and low socio-economic level in 82.5% of cases. Sixteen patients were smokers (57.14%), 5 ethyl patients (17.8%), diabetes was present in 3 patients (10.7%) and hypertension in 11 patients (39.28%). The clinico-biological picture was dominated by high systolic blood pressure in 21 cases (75%), anasarca in 7 cases (25%), proteinuria in all cases and hematuria in 20 cases (71.14%). Biology revealed nephrotic syndrome (NS) in all cases, hypercholesterolemia in 23 cases (82.14%), high serum creatinine in 14 cases (50%) with an average creatinine level of 127,95 µmol/l, anemia in 17 cases (60.7%) and anti-neutrophil cytoplasmic antibodies were positive in one case. MN was confirmed by a kidney biopsy in all cases. Symptomatic treatment was indicated in all patients. Immunosuppressive therapy was started early in 12 patients (40%) because of the severe NS and the deterioration of renal function. Eight patients (26.6%) received corticosteroids alone, three patients received corticosteroid with mycofenolate mofetil and one patient received corticosteroid with ciclosporin. Fourteen patients received only symptomatic treatment. We noted complete remission in 6 patients (21.42%) and end renal stage disease in 5 patients (17.85%). Our study showed that treatment with angiotensin receptors blockers was associated with better renal survival with a statistically significant difference, (p = 0.011). A reduced kidney function at presentation, tubule-interstitial disease and interstitial fibrosis and tubular atrophy were associated with poor survival with a statistically significant result (p = 0.012) (p=0,011) respectively. Conclusion IMN is the most common cause of nephrotic syndrome in elderly patients and it has the same risk for progression as in younger individuals. Decrements in glomerular filtration rate, increased risk for comorbidities, vascular disease and change in pharmacokinetics justify special attention to treatment decisions in elderly individuals with IMN.

Renal involvement is rare in systemic sarcoidosis. Among renal manifestations, tubulointerstitial nephritis (TIN) is the most commonly reported finding. We conducted the current study to investigate the clinical, laboratory, and histological features and to analyze the outcome of TIN due to sarcoidosis. We present a retrospective, single-center study of patients followed for sarcoidosis and presenting with TIN related to this systemic disease. Twenty-four patients were assessed (22 females/2 males). The mean age at diagnosis of TIN was 46.3 years. Extrarenal manifestations were dominated by thoracic involvement (95.8%), peripheral lymph nodes (54.2%), and skin lesions (33.3%). The mean proteinuria level was 0.68 g/24 h. Renal failure was diagnosed in 83.3% of cases with a median estimated glomerular filtration rate at 14.3 mL/min/1.73 m2. Nine patients presented with hypercalcemia and 12 patients with hypercalciuria. Renal biopsy was performed in 58.3% of cases. Six of the 14 patients presented with noncaseating granulomatous interstitial nephritis and eight with interstitial nephritis without granuloma. Granulomatous infiltration of renal parenchyma was complicated by vasculitis in two cases. Corticosteroid therapy was used in all patients. On follow-up analysis, four patients progressed to end-stage renal disease (ESRD) after a mean duration at 45.5 months. In the remaining patients, kidney function statistically significantly improved after one month of treatment compared to the time when the diagnosis was initially established (P = 0.031). We found that the predictive factors of progression to ESRD were multiorgan involvement (P = 0.032), advanced fibrosis F3 (P = 0.0006), and extensive interstitial granulomas (P = 0.007) and these were independently correlated with ESRD. Corticosteroid therapy seems to be effective in sarcoid TIN, but some degree of persistent renal failure is possible which can be predicted from both histologic findings and initial response to steroid therapy.

Th17 cell subset has been implicated in autoimmune diseases, tumor immunity and, transplant rejection. In order to investigate the role of IL-17/IL-23 pathway in allograft outcome, intragraft expression of IL-17 mRNA and single nucleotide polymorphisms (SNPs) of IL-17A, IL-17F, IL-17RC, and IL23R genes were evaluated with a quantification of IL-17A, IL-17F, and IL-23 plasma levels. This study revealed that recipients with acute rejection (AR) had a significant increase in IL-17A mRNA expression levels after transplantation compared to controls (P = 0.037). Moreover, IL-17A plasma levels were significantly higher in AR group; pretransplantation (Day–1 [D–1]): P = 0.00022 and posttransplantation (Day 7 [D7]): P < 10–14. IL-17F and IL-23 plasma levels were significantly higher in AR at D7 only (47.86 vs. 22.99 pg/ml; and 33.82 vs. 18.811 pg/ml; P = 0.015 and P < 10–17, respectively). Using receiver-operating characteristic curves, D7 IL-17A and IL-23 plasma levels exhibited excellent sensitivities and specificities for predicting AR. Genetic study revealed no association between IL-17A, IL-17F, IL-17RC, and IL23R studied SNPs and AR. Nevertheless, a significant improvement of graft survival was found in kidney transplant recipients carrying IL-17F-rs763780*A/A, IL-17RC*G/G, and *G/A genotypes. Besides, IL-17A mRNA levels were significantly higher in patients carrying the IL-23R*G/G genotype comparatively to those with *G/A genotype. Based on these findings, significant increase of IL-17A mRNA and protein levels in AR recipients that are genetically controlled highlights the role of this cytokine that can be a useful clinical biomarker to predict early acute renal allograft rejection. Study showing significant associations between Day 7 plasma IL-17A, IL-17F and IL-23 and AR with good performances for IL-17A and IL-23 in predicting acute rejection (AR) occurrence; significant increase of IL-17A expression in kidney graft in case of AR; a significant improvement of graft survival in recipients carrying IL-17F-rs763780*A/A, IL-17RC*G/G and *G/A genotypes.

Background Male breast cancer (MBC) is a rare and neglected disease. Prognostic and predictive factors in MBC are extrapoled from trials conducted on its female counterpart. Objective Since the relationship between the transcription factor Forkhead box M1 (FOXM1) expression and the clinical response to chemotherapy and hormonotherapy in MBC remains unknown, we sought to investigate the predictive value of FOXM1 in MBC. Methods FOXM1 expression was assessed in 130 MBC cases. Clinical significance was analyzed by Kaplan Meier curves, log-rank test and multivariate Cox regression analyses. Results Patients with high FOXM1 expression had a significantly lower response rate to chemotherapy (P = 0.045) and hormonotherapy (P = 0.029) than those with low FOXM1 expression. Multivariate analyses indicated that FOXM1 was an independent prognostic factor for disease free survival in MBC patients (P Conclusions FOXM1 may have a reliable predictive significance in male breast cancer and thus may become an important target for male breast cancer therapy in the near future.

Background Growing evidence have shown promise for targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling in several tumors. In female breast cancer, PD-L1 expression has been correlated with poor clinical outcome. However, whether PD-L1 has any indication for prognosis in male breast cancer (MBC) patients remains unknown. The purpose of this study was to examine the expression levels of PD-L1 in MBC and to identify the relationship between PD-L1 expression and patient survival. Methods We retrospectively identified 110 male breast cancer patients diagnosed between 2000 and 2013 at Salah Azaïz Cancer Institute. PD-L1 expression was evaluated by immunohistochemistry (IHC) using CD274 antibody. Specimens were scored as IHC low or high, when < 5% or ≥ 5% of cells were PD-L1 positive, respectively. The association between expression of PD-L1 and survival was investigated using Kaplan-Meier survival and COX proportional hazard regression analyses. Results Median follow up was 12.5 months [range 1-132 months]. High expression of PD-L1 was observed in 64.5% of MBC samples (71/110). PD-L1 expression was significantly associated with advanced clinical stage (p=0.012), higher histological grade (p=0.014), higher Ki67 expression (p=0.023) and hormone-receptor negative status (p=0.024). Patients with high PD-L1 expression had significantly shorter overall survival (OS) than patients with low expression (p=0.002, hazard ratio (HR) =5 [2.624–10.642]). Multivariate analysis identified PD-L1 as an independent prognostic factor for OS (p Conclusion Our results indicate that high PD-L1 expression may be a prognostic indicator for reduced OS. Thus, PD-L1 expression is a promising novel biomarker with prognostic significance in MBC and may suggest a potential therapeutic target of anti-PD-L1 antibody therapy in MBC patients. Citation Format: Abdeljaoued S, Bettaieb I, Adouni O, Goucha A, Chiba D, Bouzaiene H, Ben Hassouna J, Boussen H, Rahal K, Gamoudi A. Prognostic value of PD-L1 expression in male breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-05.

Secondary renal amyloidosis (RA) is the most common type of renal involvement in ankylosing spondylitis (AS). We assessed the epidemiologic and clinico-biological profile of AS patients with RA, to analyze treatment modalities and prognostic aspects, and to determine predictive factors of RA during AS. This was a retrospective study including 13 cases of RA among 212 cases who presented with AS, during the period from 1978 to 2006. The median age of the patients at the time of diagnosing AS was 47 years (range: 19-67). There were 11 males and two females. RA onset was diagnosed after a mean follow-up of 144.6 months (range: 10-505) from the AS diagnosis. We noted erosive peripheral arthritis, lumbar stiffness with bamboo spine, and coxitis in 23.1%, 76.9%, and 30.8% of cases, respectively. Nephrotic syndrome was found in eight patients (61.5%). At the time of diagnosing RA, six patients had renal failure. Amyloid deposits were histologically proven by salivary gland biopsy in six cases (46.1%) and by renal biopsy in seven cases (53.8%). Four patients received a long-course treatment with colchicine but with a good outcome only in two cases. In our series, AS was more severe among patients with RA. Four predictive factors of RA were identified: smoking (P = 0.04), erosive peripheral arthritis (P = 0.002), bamboo spine (P = 0.001), and biologic indicators of inflammation (P = 0.0001). High erythrocyte sedimentation rate was identified as the only independent risk factor of RA during AS (P = 0.0001). Renal function as well as urinalysis should be monitored at regular intervals to detect early renal involvement during AS.

Background: Several studies have outlined biological differences between female and male breast cancer (MBC) and concluded that MBC should be considered as an entirely separate disease. Whether FOXM1 has any indication for prognosis in MBC patients remains unknown. We sought to examine the expression levels of FOXM1 in MBC and to identify the relationship between FOXM1 expression and patient survival. Patients and Methods: FOXM1 expression was evaluated in a total of 130 MBC specimens. Results: FOXM1 was overexpressed in 37% of the MBC samples. FOXM1 overexpression was significantly associated with tumor size (p = 0.045), histological grade (p = 0.048), lymph node metastasis (p = 0.012), Ki-67 proliferation index (p = 0.016), and molecular subtypes (p < 0.001). Multivariate analyses indicated that FOXM1 was an independent prognostic factor for overall survival in MBC patients (p < 0.001, hazard ratio = 0.69 (0.43-0.96)). Conclusions: Overexpression of FOXM1 was associated with well-established markers of poor prognosis; thus FOXM1 may represent a potential novel prognostic marker for MBC.

Objectives Breast cancer is the most frequent female cancer. In some cases, a change in hormonal receptors and Her2neu status between primary tumors and relapsed tumors were reported. Our aim is to determine if it is mandatory to repeat immunohistochemistry and if there are some factors that can predict change of status. Methods A retrospective study about 46 patients with locoregional cutaneous or lymphatic relapse between 2015 to 2017. The patients were devided into 5 molecular subtypes: Lumina A, Luminal B, Luminal B Her2; Her2 and triple negative subtype. Results The median age was 47-year-old (IQR 27–79). Mean histologic size was 4.56 cm (IQR 0.5–13). 34 patients were grade II of SBR. 54,34%(25) of the patients had radical surgery associated to chemotherapy radiation therapy and hormonal therapy as initial treatment. A mean number of harvested metastatic lymph-nodes at initial surgery was 8.28 (0–36). 54,34% (25) had their status changed. The highest ratio of status changes was observed with luminal A tumors73.33% (11/15). Whereas triple negative tumors have the lowest ratio 16.66% (1/6). We studied the impact of age, time to relapse and site of relapse on status change, but no statistical significance was found. Conclusions Our results tend to prove the necessity of repeat immunochemistry. However, they failed to determine factors associated with higher risk of status change. Those results are to be taken with caution and further studies with bigger study population are mandatory.

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.

Background The Forkhead box M1 (FOXM1) transcription factor is known to play an important role in the development and progression of many cancer types including breast cancer. The important role of FOXM1 in cancer affirms its significance for clinical use and therapeutic intervention. Elevated expression of FOXM1 in female breast cancer correlates with undifferentiated tumor phenotype and negative clinical outcome. However, whether FOXM1 has any indication for prognosis in male breast cancer (MBC) patients is still unknown. The purpose of this study was to examine the expression levels of FOXM1 in MBC and to identify the relationship between FOXM1 expression and patient survival. Methodsl Immunohistochemical analysis for FOXM1 was performed in a total of 80 male breast cancer specimens, all with linked clinical outcome data. Kaplan-Meier method and Cox proportional hazards analysis were used to relate FOXM1 expression to clinicopathological variables and overall survival (OS). Results We observed high expression of the FOXM1 protein in 39 % of MBC samples (31/80). FOXM1 overexpression was significantly associated with higher histological grade (p=0.05), lymph node metastasis (p=0.04), tumor size (p=0.05), and estrogen receptor expression (p=0.04). Patients with FOXM1 expression had a significantly poorer overall survival than those without FOXM1 expression (p=0.02). Multivariate analyses indicated that FOXM1 positivity was an independent prognostic factor for OS (p=0.03). Conclusion These results show that FOXM1 may represent a novel MBC marker with prognostic significance that could be included into the limited marker panels for MBC. Citation Format: Rahal K, Abdeljaoued S, Bettaieb I, Bouzaiene H, Adouni O, Miladi S, Goucha A, Bouaziz H, Makhlouf R, Hechiche M, Benna F, Boussen H, El May A, Gamoudi A. Overexpression of FOXM1 is a potential prognostic marker in male breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-19-03.

Introduction: Vitamin D deficiency is frequently observed among dialysis patients. Previous studies suggested that 50 to 90% of end-stage renal disease patients are deficient in vitamin D. In Tunisia, studies regarding hypovitaminosis D in patients on dialysis are not numerous. Actually, many data support the use of native vitamin D in hemodialysis (HD) patients. In Tunisia, using native vitamin D is not part of therapeutic habits of all dialysis centers. Objectives: The aim of this study was to determine the prevalence of vitamin D deficiency in patients with chronic kidney disease stage 5 undergoing HD and to evaluate the effect of oral cholecalciferol supplementation, in intact parathormone (iPTH), serum calcium and serum phosphorus. Patients and Methods: We conducted a pre-experimental study among HD patients. Monthly oral supplementation with Cholecalciferol, was instituted for six months. Results: Forty-three participants were included. The mean 25-hydroxy vitamin D concentration was 17.89 ng/mL. Vitamin D deficiency was observed in 83.7% of our patients. We observed a significant increase in 25-hydroxy vitamin D and calcium levels and a significant decline in iPTH levels. No evidence of toxicity, nor severe hypercalcemia or hyperphosphatemia was noted. Conclusion: The supplementation with cholecalciferol seems reasonable and well tolerated in HD patients if reasonable doses are used with regular monitoring.

BackgroundPrimary membranous nephritis (PMN) is an autoimmune disease induced by the deposit of antibodies (Ab) to the phospholipase receptor A2 receptor (PLA2R) on podocytes. In this context, we aimed to assess the relationships between anti-PLA2R Ab, PLA2R rs4664308 SNP, PLA2R mRNA levels and PMN susceptibility and outcome.MethodsSixty-eight PMN patients, 30 systemic lupus erythematosus (SLE) patients with secondary MN and 30 healthy control subjects served for anti-PLA2R Ab measurement by ELISA and PLA2R rs4664308 SNP genotyping by a commercial real-time PCR. Twenty patients with tubulo-interstitial nephritis (TIN) were used as controls for renal PLA2R mRNA quantification in PMN patients from kidney biopsies. PLA2R mRNA quantification was carried-out by real-time PCR after RNA extraction.ResultsForty-three (63.2%) PMN patients received initial therapy consisting of alternating monthly cycles of corticosteroids and cyclophosphamide. Twelve (17.6%) patients had resistant PMN to initial therapy and were consecutively treated by cyclosporine or tacrolimus. Anti-PLA2R Ab were positive in 54 (79.4%) PMN patients, while all SLE patients and controls were negative, pConclusionAnti-PLA2R Ab and renal PLA2R mRNA could be useful markers for PMN outcome predicting. The PLA2R rs6446308 SNP is associated with PMN susceptibility in Tunisians.

La néphropathie de la vascularite à IgA conditionne le pronostic de cette affection chez l’adulte. Le but de notre étude était d’étudier les caractéristiques cliniques de cette atteinte rénale chez l’adulte et d’identifier les facteurs de pronostic rénal. Il s’agit d’une étude monocentrique rétrospective portant sur les patients ayant une vascularite à IgA (purpura rhumatoïde) (critères de l’EULAR) avec une atteinte rénale prouvée histologiquement et classée selon la classification de Pillebout. Nous avons analysé la survie rénale et identifier les facteurs de pronostic rénal. Vingt cinq patients ont été inclus (genre ratio M/F = 2,57) d’âge moyen au diagnostic du purpura rhumatoïde de 35,76 ans. Un purpura était présent dans 100% des cas avec une atteinte articulaire dans 28%. Une insuffisance rénale était présente dans 44% des cas. La classification histologique la plus fréquente était la classe II. Une rémission clinique a été observée dans 44% des cas et une évolution vers le stade terminal de l’insuffisance rénale chronique dans 36% des cas. La survie rénale à 195 mois était de 57%. Les facteurs pronostiques identifiés étaient l’atteinte digestive (p = 0,022), l’insuffisance rénale initiale (p = 0,0004), la classification glomérulaire (p = 0001) et la sévérité des lésions histologiques, le traitement par bloqueurs du système rénine angiotensine (p = 0,01) et les échanges plasmatiques (p = 0,03). Notre étude montre que l’atteinte rénale au cours des vascularites à IgA peut être relativement sévère avec un mauvais pronostic rénal. L’identification des facteurs pronostiques cliniques et histologiques pourrait guider l’élaboration d’études thérapeutiques prospectives.

Introduction La glomerulonephrite a depots non organises non Randall d’immunoglobuline monoclonale (PGNMID) est une gammapathie monoclonale de signification renale de decouverte recente. Elle est rare et son etiopathogenie n’est pas encore connue. Nous rapportons un nouveau cas de PGNMID associe a un myelome multiple. Observation Mme SC âgee de 57 ans, hypertendue, operee pour cancer du sein gauche, pour lequel elle a recu une chimiotherapie, une radiotherapie locoregionale et une hormonotherapie adjuvante, etait admise pour bilan etiologique d’œdemes des membres inferieurs evoluant dans un cadre d’alteration de l’etat general. Elle rapportait par ailleurs des epigastralgies, et un amaigrissement non chiffre. L’examen physique avait objective une hypertension arterielle a 150/80, des œdemes des membresinferieurs blancs mous gardant le godet et une hematurie a trois croix a la bandelette urinaire. Le bilan biologique avait montre un syndrome inflammatoire, une insuffisance renale aigue avec une clearance a 18,3 ml/mn (MDRD), une anemie hypochrome microcytaire, un syndrome nephrotique, une proteinurie de 24H a 7,5 g et une gammapathie monoclonale de type IgG kappa avec diminutiondes IgA. Le bilan phosphocalcique etait sans anomalies. Au cours de l’hospitalisation, la fonction renale de la patiente s’est rapidement degradee avec apparition d’une oligoanurie, necessitant le recours a des seances d’hemodialyse. La ponction sternale avait objective une plasmocytose a 12 %. Le diagnostic de myelome multiple symptomatique stade 3B selon Durie et Salmon a ete pose. Devant le syndrome nephrotique avec insuffisance renale, une ponction biopsie renale (PBR) a ete realisee. La PBR avait montre une glomerulonephrite membranoproliferative, avec a l’immunofluorescence des depots non organises d’IgG, kappa et de C3, rouge congo negatifs, de localisation glomerulaire exclusive, cadrant avec une PGNMID. La cryoglobulinemie etait negative. Le taux serique de C3 etait bas. Notre patiente a eu un traitement d’induction par bortezomib, dexamethasone et thalidomide, suivi d’une autogreffe de cellules souches hematopoietique. Des les premieres semaines de traitement, une amelioration de la fonction renale et de l’albuminemie etait notee, avec une reduction de la proteinurie et reprise de la diurese. Une reponse hematologique a ete objectivee au myelogramme et a l’ immunoelectrophorese. Discussion La PGNMID est une gammapathie monoclonale de signification renale rare, le plus souvent constituee d’une immunoglobuline entiere, IgG3 kappa. Pour retenir le diagnostic, il faut eliminer d’abord les autres glomerulonephrites a depots monoclonaux d’immunoglobulines : amylose, maladie de Randall et cryoglobulinemie. Notre patiente, aux antecedents de cancer du sein, presente une PGNMID associee a un myelomemultiple. Dans la litterature, l’association documentee de la de PGNMID avec une hemopathie maligne ou une neoplasie solide n’est pas frequente : seulement six cas de myelome multiple associe et cinq cas de neoplasie solide associee (2 cancer du colon, 2 cancers anorectaux, un cancer du sein avec un cancer de la vessie) ont ete decrits. La reprise de la diurese de notre patiente, la normalisation de son bilan renal et de son albuminemie ainsi que la normalisation de l’immunoelectrophorese et du myelogramme traduisent une remission hematologique et renale. Conclusion La PGNMID est une entite de decouverte recente, qu’il faut evoquer devant un syndrome nephrotique. La confirmation du diagnostic repose sur la PBR. Un traitement ciblant le clone B sous-jacent, parfois non detectable par les techniques usuelles, est indispensable pour preserver le pronostic renal.

The sarcoidosis is a systemic granulomatosis affecting most frequently the lungs and the mediastinum. An acute renal failure reveals exceptionally this disease. It’s a retrospective study implicating 13 cases of sarcoidosis complicated of acute renal failure. The aim of this study is to determine epidemiological, clinical, biological and histological profile in these cases and the interest of considering sarcoidosis diagnosis in case of unexplained renal failure. Extra-renal complications, therapeutic modalities and the outcome were determined in all patients. Our series involved 13 women with an average age of 41 years. Biological investigations showed an abnormal normocalcemia in 8 cases, a hypercalcemia in 5 cases, a hypercalciuria in 11 cases and polyclonal hypergammaglobulinemia in 7 cases. An acute renal failure was found in all patients with a median creatinin of 540 umol/L. The renal echography was normal in all patients. The kidney biopsy performed in all patients showed tubulo-interstitial nephritis. The extra-renal signs were: pulmonary interstitial syndrome in 5 cases, a sicca syndrome in 4 cases, mediastinal lymphadenopathy in 2 cases, a lymphocytic alveolitis in 3 cases, an anterior granulomatous uveitis in 3 cases and a polyarthritis in 6 cases. Six patients benefited from hemodialysis. The treatment consisted of corticosteroid in all cases. The follow up was marked by complete resolution of clinical and biological signs. The diagnosis of renal sarcoidosis should be made rapidly in order to avoid end stage renal failure.

Background Genetic polymorphisms of interleukin (IL)-17F, associated with functional and/or quantitative change in this glycoprotein, have been described as predisposing to various autoimmune diseases. The proinflammatory IL-17 has some roles in renal transplantation. In this context, the relationship between the most common IL-17F polymorphisms with acute renal allograft rejection susceptibility in Tunisian renal recipients has been investigated. Methods We examined 93 renal transplant recipients who were enrolled and classified as follows: GI, 48 transplant recipients who developed at least one episode of acute rejection; and GII, 45 controls, kidney recipients who also were followed for at least 1 year and had stable renal function. Single nucleotide polymorphisms (SNPs) of IL-17F gene, including -1507 C/T (rs18889570), 7384 A/G (rs2397084), 7469 C/T (rs11465553), and 7489 A/G (rs763780), were evaluated using direct sequencing. Results No statistically significant association of the IL-17F SNPs studied with the onset of acute rejection was observed. However, AA genotype on 7489A/G SNP showed anti-HLA antibodies less than other genotypes and a higher graft survival time (P = .017). Conclusion The AA genotype on 7489A/G SNP of IL-17F and the A allele might be associated with a lower risk of acute rejection with better graft survival.

Renal involvement in Takayasu's arteritis is frequent and worsens the progression of the disease. This is primarily a renal artery stenosis causing renovascular hypertension. The glomerular disease is exceptional. This study was undertaken to determine the clinical, radiological, biological features and therapeutic response in patients with kidney disease associated with Takayasu arteritis. A retrospective chart review was conducted on 11 patients (five men and six females), with a mean age of 31.1 years (19-40 years). The discovery of kidney disease preceded the diagnosis of Takayasu's arteritis in eight cases. Ten patients developed hypertension. Laboratory finding showed proteinuria in five cases of which one case was due to nephrotic syndrome. Renal failure was found in six cases including four cases in stage of terminal chronic renal failure. Impairment of the renal artery was present in nine patients, proximal in seven cases and distal in two cases, bilateral in five cases and unilateral in four cases. Narrowing renal artery was found in seven cases. The renal biopsy revealed membranoproliferative glomerulonephritis in one case and nephrosclerosis in another case. Eleven patients were followed for an average period of 155 months (3-335 months). Remission of nephrotic syndrome was concomitant with the remission of the disease. Seven patients developed outbreaks of Takayasu's arteritis of which six were in care. Relapse of nephrotic syndrome was concomitant with the outbreak of the disease followed by spontaneous remission of both diseases. Improved pressure was obtained in 5 cases and worsening renal function in seven cases. Death was observed in two cases.

Euphorbia paralias is known in traditional medicine as an anti-inflammatory agent, a purgative and for its local anesthetic property. To the best our knowledge, renal toxicity of this substance has not been previously reported. In this paper, we report the case of a 29-year-old male who developed renal damage following ingestion of Euphorbia paralias. He had been on follow-up for nephrotic syndrome since 1986, although irregularly, with several relapses but each responding well to steroid therapy. A kidney biopsy had not been performed earlier due to refusal by the patient. He was off steroids since April 2008 because the patient developed osteoporosis. He was admitted with general malaise and oliguria to our department in May 2009, following repeated vomiting and watery diarrhea for three days. On examination, he was edematous but had normal vital signs except for a pulse rate of 120/min. Hemoglobin was only 5.5 g/dL but with normal white cell and platelet counts. Blood biochemistry showed evidence of advanced renal failure with a serum creatinine level of 1835 μmol/L and urea at 44.6 mmol/L, sodium of 132 μmol/L and potassium at 4.3 mmol/L. He had features of nephrotic syndrome with severe hypoproteinamia and 24-h urinary protein of 10.45 g. Ultrasonography revealed enlarged kidneys with a reduced echogenecity of the medulla and the papillae. Subsequently, after hemodialysis with blood transfusion, a kidney biopsy was performed that showed focal segmental glomerulosclerosis associated with an acute tubular injury. On intensive interrogation, the patient gave a history of ingesting boiled Euphorbia paralias as a native treatment for edema, ten days prior to the onset of the current illness. A diagnosis of acute renal failure (ARF) resulting from the possible nephrotoxic effect of Euphorbia paralias poisoning was made. He was treated with intermittent hemodialysis and corticosteroids. Serum creatinine values improved after 48 days. At six months following the intoxication, serum creatinine of the patient was 240 μmol/L. In cases of unexplained ARF, a toxic mechanism should always be considered and acute renal failure caused by Euphorbia paralias should be included as a cause if renal toxicity is suspected in those places where it is being used as a native medicine.

Aim The objective is to report the correlation between pathology and molecular subtype classifications of breast cancer in Tunisian women. Methods 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. Results 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