Publications by authors named "Nadia Boujelbene"

33 Publications

Meta-analysis of HLA-G 14bp insertion/deletion polymorphism and soluble HLA-G revealed an association with digestive cancers initiation and prognosis.

Heliyon 2022 Jul 19;8(7):e09986. Epub 2022 Jul 19.

Laboratory Microorganisms and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia.

Background/objective: Conflicting results on the association between HLA-G and digestive cancers were reported. We conducted a meta-analysis to further investigate the true relationship between HLA-G and digestive cancers (DC).

Methods: Following PRISMA guidelines, we performed a meta-analysis including 7 case-control studies on HLA-G 14-bp Insertion/deletion (I/D) polymorphism, and 15 studies on soluble HLA-G (sHLA-G). Odds ratios (OR) and their corresponding 95% confidence intervals (CI) for genetic polymorphisms were calculated. The pooled OR was calculated under three genetic models: allelic, recessive, and dominant models. Concerning sHLA-G meta-analysis, standardized mean differences (SMDs) were calculated.

Results: The HLA-G 14-bp I/D was not associated with the risk of DC. However, in the subset of HBV/HCV positive hepato-cellular cancer (HCC) patients, we reported a significant association of HLA-G 14-bp I/D with the disease initiation under allelic (D vs. I; OR = 1.698, 95% CI = 1.263-2.282, p = 0.000), dominant (DD + ID vs. II; OR = 2.321, 95% CI = 1.277-4.218, p = 0.006)and recessive (DD vs. DI + II; OR = 1.739, 95% CI = 1.173-2.577, p = 0.006) genetic models. Interestingly, HLA-G 14-bp I/D was not associated with the disease initiation in HBV/HCV negative HCC patients. However, the infection by HBV/HCV seems to be implicated in the HCC development when we compared HBV/HCV positive patients to HBV/HCV negative patients under allelic (D I; OR = 1.429, 95% CI = 1.029-1.983, p = 0.033, and dominant (DD + ID II; OR = 1.981, 95% CI = 1.002-3.916, p = 0.049) genetic models.Overall analysis of DC showed significant increased sHLA-G in patients compared to healthy controls (SMD = 3.341, 95% CI = 2.415-4.267, p = 0.000). In Asian patients with gastric cancer, sHLA-G was significantly increased in grade 3 compared to low grades (SMD = 0.448, 95% CI = 0.109-0.787, p = 0.000). Further analysis showed that sHLA-G was significantly increased in positive DC vascular invasion (SMD = 0.743, 95% CI = 0.385-1.100, p = 0.000). Accordingly, sHLA-G was associated with a poor prognosis for DC.

Conclusion: The current meta-analysis supports the significant role of HLA-G in DC. The HLA-G 14-bp I/D polymorphism was associated with HCC patients with concomitant HBV/HCV viral infections. Increased sHLA-G indicated a poor prognosis for DC cancer patients.
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http://dx.doi.org/10.1016/j.heliyon.2022.e09986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305369PMC
July 2022

The relationship of 3'UTR HLA-G14-bp insertion/deletion and +3142 C/G polymorphisms and soluble HLA-G expression with gynecological cancers: An updated meta-analysis.

Immun Inflamm Dis 2022 07;10(7):e645

Laboratory Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, Tunisia.

Objectives: Human leukocyte antigen-G (HLA-G) is implicated in several cancers and is considered to be an immune checkpoint regulator. We determined the association between polymorphisms in the 3' untranslated region of HLA-G and soluble HLA-G (sHLA-G) expression with gynecological cancers (GCs).

Methods: A meta-analysis was conducted to examine the association between HLA-G14-bp insertion (I)/deletion (D) and +3142C/G polymorphism in GC and to evaluate sHLA-G expression RESULTS: We revealed a significant association between the +3142C/G polymorphism and invasive cervical cancer (ICC) based on the allelic model G versus C (odds ratio [OR] = 0.738, 95% confidence interval [CI] = 0.563-0.966, p = 0.027), dominant GG+GC versus CC (OR = 0.584, 95% CI = 0.395-0.862, p = 0.007), and codominant GG versus CC (OR = 0.527, 95% CI = 0.312-0.891, p = 0.017) models, suggesting that the G allele and GG genotype are protective against ICC. In gynecological precancerous patients with human papillomavirus (HPV) infection, we found that the 14-bp I/D under the codominant DD versus DI model (OR = 0.492, 95% CI = 0.241-1.004, p = 0.051) was of borderline significance. Soluble HLA-G levels were significantly higher in patients compared with healthy controls (standardized mean differences [SMD] = 1.434, 95% CI = 0.442-2.526, p = 0.005). Stratification by cancer type revealed that the sHLA-G levels were significantly increased in cervical cancer (SMD = 4.889, 95% CI = 0.468-9.310, p = 0.030) and in subjects of Asian ethnicity (SMD = 4.889, 95% CI = 0.467-9.309, p = 0.030).

Conclusions: HLA-G14-bp I/D and +3142 C/G polymorphisms are associated with GC and HPV-associated cervical cancer. In addition, we found significantly increased sHLA-G levels in cancer patients. These results provide a basis for further studies in diagnostics and immunotherapy of GC.
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http://dx.doi.org/10.1002/iid3.645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168547PMC
July 2022

3'UTR-HLA-G polymorphisms and circulating sHLA-G are associated with breast cancer: Evidence from a meta-analysis.

Immunol Lett 2022 Aug 22;248:78-89. Epub 2022 Jun 22.

Laboratory Microorganisms and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia. Electronic address:

Background: Human leukocyte antigen-G (HLA-G) gene polymorphisms and circulating sHLA-G have often been linked to the risk of breast cancer (BC). However, the results remain controversial. To resolve this issue, we performed a meta-analysis of HLA-G gene polymorphisms and sHLA-G levels in BC.

Methods: We performed a meta-analysis on the association of HLA-G 14-bp Insertion/Deletion (Ins/Del) and HLA-G +3142 C/G polymorphisms with BC as well as the relationship between sHLA-G and the disease outcome.

Results: Pooled analysis showed a statistically significant association between the HLA-G 14-bp Ins/Del polymorphism and BC susceptibility for the overall population and for Caucasians. The Del allele and genotypes with at least one copy of the Del allele presented significant risks for BC. For HLA-G +3142 C/G polymorphism, the G allele significantly decreased the risk of BC for the overall population and for Caucasians, indicating that the G allele was a protective factor against BC and that the C allele was a significant risk factor for BC. The meta-analysis revealed a significantly increased level of sHLA-G patients with BC compared to the control group for the overall population, Caucasians and Asians.

Conclusion: The present meta-analysis showed a major association of both HLA-G 14-bp Ins/Del and +3142 C/G polymorphisms with BC susceptibility, suggesting Del and C variants as highly significant risk factors for BC. The present study also showed significantly higher sHLA-G levels in patients with BC compared to healthy controls. Our pooled results suggested a critical role of HLA-G in BC, thereby providing evidence to use HLA-G as a biomarker and a therapeutic tool.
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http://dx.doi.org/10.1016/j.imlet.2022.06.010DOI Listing
August 2022

Puzzling hepatic tumor: Epithelioid angiomyolipoma.

Clin Case Rep 2022 Jan 28;10(1):e05327. Epub 2022 Jan 28.

Tunis Faculty of Medicine University of Tunis El Manar Tunis Tunisia.

Hepatic epithelioid angiomyolipomas are uncommon mesenchymal neoplasms. They are difficult to diagnose by imaging, especially when the fatty component is scant or absent. The gold standard for the diagnosis is histologic examination coupled with an immunohistochemical study. Positive HMB45 immunostaining of the myoid cells is a major diagnostic feature.
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http://dx.doi.org/10.1002/ccr3.5327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795920PMC
January 2022

[Pseudoxanthomatous salpingitis].

Ann Pathol 2022 07 6;42(4):351. Epub 2022 Jan 6.

Service d'anatomie et de cytologie pathologiques, institut Salah-Azaiez, Tunis, Tunisie; Laboratoire de microorganismes et biomolécules actives, faculté de médecine de Tunis, université Tunis-El-Manar, Tunis, Tunisie.

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http://dx.doi.org/10.1016/j.annpat.2021.07.001DOI Listing
July 2022

Cystic Lymphangioma of the Small Bowel Mesentery in a Child.

J Pediatr 2022 05 23;244:248-249. Epub 2021 Dec 23.

Department of Pediatric Surgery "A", Children's Hospital, Tunis El Manar University, Tunis, Tunisia.

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http://dx.doi.org/10.1016/j.jpeds.2021.12.032DOI Listing
May 2022

Association of HLA-G 3'UTR polymorphisms and haplotypes with colorectal cancer susceptibility and prognosis.

Hum Immunol 2022 Jan 9;83(1):39-46. Epub 2021 Nov 9.

Laboratory Microorganisms and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia. Electronic address:

Human leukocyte antigen (HLA)-G has been considered as an immune modulator in several types of cancers. Its genetic polymorphisms may potentially affect the risk of developing colorectal cancer (CRC). The overall purpose of this study was to analyze the implication of HLA-G 3'untranslated region (3'UTR) polymorphisms particularly 14 pb insertion/deletion (Ins/Del; rs371194629) and + 3142C/G (rs1063320) in CRC susceptibility and progression. A comparative analysis between patients (N = 233) and controls (N = 241) demonstrated that Del allele (Odds Ratios (OR) = 1.41, 95% CI = 1.091-1.819, p = 0.008), the homozygous Del/Del genotype (OR = 1.80, 95% CI = 1.205-2.664, p = 0.003) and the codominant C/G genotype (OR = 1.59, 95% CI = 1.106-2.272, p = 0.013) were associated to CRC risk. As expected, the DelG haplotype was associated with CRC susceptibility (OR = 1.47, 95% CI = 1.068-2.012, p = 0.018). Assessment of patients' survival by Kaplan-Meier analysis indicated that the Del allele and the homozygous Del/Del genotype were associated with reduced event free survival (EFS) (Respectively, p = 0.009 and p = 0.05). Interestingly, the Del allele and the homozygous Del/Del genotype have been revealed as independent prognostic factors for poor EFS in patients with CRC. Additionally, haplotypes analysis revealed that DelG haplotype was linked with significant increase in CRC risk (log-rank; EFS: p = 0.02). Inversely, the InsC haplotype was associated with a significant reduced CRC risk (log-rank; Overall survival (OS): p < 10; EFS: p = 0.01). Multivariate Cox regression analysis revealed that the InsC haplotype was independently associated with significantly longer EFS (p = 0.021, HR = 0.636, 95% CI = 0.433-0.935). These findings support the implication of HLA-G polymorphisms in the CRC susceptibility suggesting HLA-G as a potent prognostic and predictive indicator for CRC. Insight into mechanisms underlying HLA-G polymorphisms could allow for the development of targeted care for CRC patients according to their genetic profile.
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http://dx.doi.org/10.1016/j.humimm.2021.10.003DOI Listing
January 2022

Prognostic significance of high circulating sHLA-G in ovarian carcinoma.

HLA 2021 10 26;98(4):357-365. Epub 2021 Jul 26.

Laboratory Microorganismes and Active Biomolecules, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia.

HLA-G is a non-classical major histocompatibility complex class Ib molecule. Its expression has been described in various cancer types, including ovarian cancer. HLA-G molecule has been implicated in immune escape and in progression of ovarian tumor cells. Our goal was to assess if total soluble (s)HLA-G molecules or HLA-G5 and sHLA-G1 isoforms could be considered as circulating ovarian tumor biomarkers, we measured the concentration of these molecules in ovarian carcinoma patients stratified according with their clinicopathological parameters. sHLA-G, sHLA-G1 and HLA-G5 concentrations were dosed in plasma samples by sandwich-ELISA. The sHLA-G dimerization was analyzed after immunoprecipitation and SDS-PAGE migration. Total sHLA-G and sHLA-G1 levels were significantly represented in plasma of ovarian carcinoma patients compared to healthy controls. sHLA-G1 isoform concentration was highly represented in ovarian carcinoma compared to HLA-G5 isoforms. Additionally, high sHLA-G molecules have been found in aged patients, as well as in patients with advanced stages, and those with metastatic lymph nodes and those with distant metastasis. Elsewhere, sHLA-G monomers were highly represented in ovarian carcinoma patients compared to controls. sHLA-G plasmatic protein was highly represented in ovarian carcinoma. In effect, HLA-G might be considered as a new checkpoint molecule that could be used to assess progression and recurrence of the disease, thus placing it as a potential biomarker for advanced and complicated ovarian carcinoma.
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http://dx.doi.org/10.1111/tan.14374DOI Listing
October 2021

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma: clinicopathological study and treatment outcome in 50 patients.

Pan Afr Med J 2020 23;37:372. Epub 2020 Dec 23.

Pathology Department, Salah Azaiez Institute, Tunis, Tunisia.

The stomach is the most frequent site of extranodal lymphoma. Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade, B-cell neoplasm strongly associated with Helicobacter pylori (HP) infection. The presenting complaints of gastric MALT lymphoma are usually nonspecific. HP eradication is regarded as the first-line therapy in early stage disease. Management of patients who failed to achieve remission following HP eradication include chemotherapy, radiotherapy and in selected cases, surgery. The aim of the present study was to examine the clinical characteristics and treatment outcome of patients with gastric MALT lymphoma.
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http://dx.doi.org/10.11604/pamj.2020.37.372.27094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992398PMC
April 2021

[A distinct breast tumor in an elderly woman].

Ann Pathol 2021 Apr 23;41(2):228-230. Epub 2021 Jan 23.

Service d'anatomie et cytologie pathologiques, institut Salah Azaiez, Bab Saadoun, 1006 Tunis, Tunisie.

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http://dx.doi.org/10.1016/j.annpat.2020.09.003DOI Listing
April 2021

Expression analysis of immune-regulatory molecules HLA-G, HLA-E and IDO in endometrial cancer.

Hum Immunol 2020 Jun 6;81(6):305-313. Epub 2020 Apr 6.

Laboratory Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia. Electronic address:

HLA-G has been widely implicated in advanced cancers through different pathways of immunosuppression allowing tumor escape. Contrarily, HLA-E has a controversial role in the tumor escape from the immune system. IDO catabolic enzyme is known to be up-regulated in many tumors types allowing their immune escape. Based on these considerations, we investigated the expression of HLA-G, HLA-E and IDO molecules in endometrial cancer (EC) and their association with prognostic clinicopathologic parameters. Their expression were checked in tumoral and adjacent endometrial tissues. Both HLA-G and IDO immunostaining were significantly increased in EC tissues compared to normal residual endometrial glands (Mann Whitney U-test, p = 0.0001 and p = 0,020 respectively). However, HLA-E was highly expressed in tumoral tissues as well as in normal residual endometrial glands (respectively, 100% and 81.8%). Increased HLA-G expression levels were observed in high histological grade (grade 3), and in the non-endometrioid type 2 EC. Unexpectedly, patients with IDO Low expression had significantly impaired overall survival compared to patients with IDO High (log-rank p = 0.021). Conversely, HLA-E low expression was associated to an improved overall survival EC (log-rank p = 0.004). We concluded that, HLA-G and IDO are highly expressed in EC compared to adjacent normal endometrial tissues, that might be interesting for the EC outcome.
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http://dx.doi.org/10.1016/j.humimm.2020.03.008DOI Listing
June 2020

Clear cell sarcoma of the esophagus: A rare location.

Clin Case Rep 2020 Feb 22;8(2):323-326. Epub 2019 Dec 22.

Medical Oncology Department Faculty of Medicine of Tunis Salah Azaiez Institute El Manar University Tunis Tunisia.

Clear cell sarcoma of the esophagus is very rare. The etiology of this neoplasm remains unknown. Confirmed diagnosis requires histopathology with immunochemistry and molecular study. CCS typically shows highly aggressive behavior with a high rate of local recurrence, metastases, and death from disease.
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http://dx.doi.org/10.1002/ccr3.2620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044402PMC
February 2020

Mismatch Repair Deficiency in Endometrial Cancer: Immunohistochemistry Staining and Clinical Implications.

Appl Immunohistochem Mol Morphol 2019 10;27(9):678-682

Department of Pathology, Salah Azeiz Institute, Tunis, Tunisia.

Introduction: DNA mismatch repair (MMR) deficiency is associated with increased risk of developing several types of cancer and is the most common cause of hereditary endometrial cancer. Identification of the microsatellite instability (MSI) phenotype in endometrial carcinoma is important given that such tumors are frequent.

Objective: The objective of this study was to assess the utility of immunohistochemistry (IHC), a simple and fast technique, in detecting MSI status in endometrial carcinoma and evaluate the correlation between the MSI phenotype and the various anatomo-clinical parameters.

Methods: IHC expression of 4 markers (MLH1, MSH2, PMS2, and MSH6) was studied. For all IHC markers, a combined score based on the intensity of nuclear labeling and the percentage of labeled cells was defined to establish a score. Correlation between MSI phenotype and different clinicopathologic parameters was evaluated using statistical analysis (software STATA and the Fisher exact test).

Results: The mean age of the patients was 58.6 years. Positive staining was highly extended (score 3) with 79% to 100% of marked cells. Less than 10% of positive tumor cells were seen in 3% of cases for MSH6 and PMS2. Abnormal MMR IHC was detected in 10 cases (22.22%). Seven tumors showed loss of MLH1/PMS2. The loss of MSH2/MSH6 was observed in 1 case. The loss of MLH1 or PMS2 was seen only in 2 cases. The number of MSI positive status was 10 cases (22.7%). Correlation between clinicopathologic parameters showed MMR deficiency was significantly associated with low-grade tumor and localized stage. There was no positive correlation between age, histologic subtype, or myometrium invasion.

Conclusions: In summary, detection of DNA MMR deficiencies by IHC can effectively diagnose the MSI phenotype in endometrial carcinoma. Correlation between clinicopathologic parameters showed MMR deficiency was significantly associated with low-grade tumor and localized stage.
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http://dx.doi.org/10.1097/PAI.0000000000000641DOI Listing
October 2019

Prognostic factors and the role of pelvic lymphadenectomy in uterine leiomyosarcomas.

SAGE Open Med 2019 13;7:2050312119856817. Epub 2019 Jun 13.

Department of Surgical Oncologists, Salah Azaiez Institute, Tunis, Tunisia.

Objectives: Leiomyosarcomas are relatively rare uterine smooth muscle tumors. Surgery is the most common therapy choice for uterine leiomyosarcomas. However, controversy exists over the appropriate initial surgical management, especially about the role of lymph node sampling. The aim of our study is to analyze the prognostic factors and the role of lymphadenectomy in overall survival and in disease-free survival.

Methods: We analyzed retrospectively 31 patients suffering from uterine leiomyosarcomas at Institute of Salah Azaiez during 2000-2014. Demographic and clinical features such as age, menopausal status, stage, tumor size, and management options were examined, and pathological characteristics such as mitotic count, lymphovascular space invasion, and tumor necrosis were evaluated.

Results: Out of 31 patients treated for uterine leiomyosarcomas, pelvic lymphadenectomy was done for 18 patients. No para-aortic lymphadenectomy was performed. Median number of resected lymph nodes was 13 ± 7 (range: 3-27). Lymphatic metastasis was observed in 2 out of 18 patients with clinical stage IA and IIIB. The distribution of different variables (age, International Federation of Gynecology and Obstetrics stage, tumor size, mitotic count, and adjuvant treatment) between the group of patients, who had or had not lymphadenectomy done, had no significant difference. The 5-year overall survival and disease-free survival were 61% and 50%, respectively. Clinical stage, presence of lymphovascular space invasion, and lymph nodal dissection were found to be relevant for disease-free survival on univariate analysis. Only age and menopausal status were found to be a prognostic factor for overall survival.

Conclusion: Hence, routine lymph node dissection was not generally recommended. Our study demonstrates that lymphadenectomy has a statistically significant effect on disease-free survival but not on overall survival.
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http://dx.doi.org/10.1177/2050312119856817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572874PMC
June 2019

HLA-G, HLA-E, and IDO overexpression predicts a worse survival of Tunisian patients with vulvar squamous cell carcinoma.

HLA 2019 07 30;94(1):11-24. Epub 2019 Apr 30.

Laboratory Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia.

Little is known about non-classical HLA molecules in vulvar squamous cell carcinoma (VSCC). Because of the indoleamine-2,3-dioxygenase (IDO) immune tolerant role in association with HLA-G, we evaluated the clinical and prognostic value of HLA-G, HLA-E, and IDO in VSCC. HLA-G, HLA-E, and IDO expression was determined by immunohistochemistry in VSCC and associated with clinicopathological parameters and disease outcome. These three molecules were highly represented in tumoral tissues vs healthy matched vulvar tissues (P = 0.0001). Significant differences in HLA-G expression in stages, tumor size, tumor invasion depth, and resection margins subgroups were reported (P < 0.05). At 5 years, the cumulative survival rates was of 79.8% in patients with HLA-G expression vs 12.5% in those with HLA-G expression (P < 3 × 10 ). Similarly, patients with IDO expression were at a significantly reduced overall survival (OS) and disease-free survival (DFS) rates (P = 0.011 and 0.045, respectively). The overexpression of the three molecules together worsen survival rates of VSCC patients (OS: P = 0.000038, DFS: P = 0.000085). Altogether, our results showed that HLA-G, HLA-E, and IDO may represent novel candidate markers for patients' prognosis and potential targets for VSCC therapy.
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http://dx.doi.org/10.1111/tan.13536DOI Listing
July 2019

Gelatinous Transformation of Bone Marrow in a Patient with Anorexia Nervosa: An Uncommon but Reversible Etiology.

Am J Case Rep 2018 Dec 7;19:1449-1452. Epub 2018 Dec 7.

Department of Internal Medicine B, Charles Nicolle Hospital, Tunis, Tunisia.

BACKGROUND Anorexia nervosa is a relatively frequently encountered eating disorder. Beyond its psychiatric significance, it is associated with multiple hematological features such as cytopenia. It can be related to gelatinous transformation of the bone marrow. CASE REPORT We describe the case of a 20-year-old male admitted for rapid involuntarily weight loss. He presented with extreme bradycardia with a heart rate of 30 beats per minute with recent psychomotor impairment. Routine laboratory tests showed pancytopenia, and cytolysis on liver function tests. Cardiac investigations did not reveal abnormalities except for sinus bradycardia. Bone marrow aspirate revealed hypo-cellular marrow with infiltration by gelatinous substance. In addition, bone marrow biopsy showed fat cell atrophy along with loss of hematopoietic elements in areas of gelatinous transformation. During the patient's hospital stay, he had a restrictive oral diet. Thus, after consulting with a psychiatric specialist, a diagnosis of anorexia nervosa complicated with gelatinous transformation of bone marrow, bradycardia, and acute hepatitis was made. After psychiatric treatment and nutritional care, the patient regained weight, had a normal heart rate and normal liver function tests, and his full blood count and bone marrow examination were within normal range. CONCLUSIONS Gelatinous transformation of bone marrow can be the revealing feature of anorexia nervosa and some potentially reversible associations might prove life threatening if misdiagnosed. Furthermore, lack of suspicion can lead to unwarranted investigations increasing the cost incurred in healthcare delivery. Our patient had 3 systems involved: cardiac, hepatic, and hematological systems. Gelatinous transformation of bone marrow, although a rare condition, must be considered in such patients.
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http://dx.doi.org/10.12659/AJCR.911287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293863PMC
December 2018

Hemochromatosis associated with cholelithiasis as a cause of hydrops fetalis and stillbirth: Prenatal diagnosis.

J Clin Ultrasound 2019 Jan 30;47(1):47-50. Epub 2018 Oct 30.

Department of Embryo-Fetopathology, Maternity and Neonatology Center, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.

Prenatal diagnosis of neonatal hemochromatosis (NH) is usually raised in front of fetal hepatomegaly and heterogeneous liver architecture. We describe a novel sonographic feature that may be associated with NH. Ultrasound demonstrated reticulonodular liver and distended gallbladder with multiple gallstones in a hydropic fetus. These abnormalities were confirmed to be consistent with NH after correlation with autopsy findings. This case report highlights the value of cholelithiasis in clinical suspicion of NH and the importance to consider this sonographic feature when the liver has abnormal texture.
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http://dx.doi.org/10.1002/jcu.22653DOI Listing
January 2019

Analysis of prognostic factors of nephroblastoma in a Tunisian cohort.

Tunis Med 2018 Mar;96(3):193-202

Background: Nephroblastoma is the most common childhood abdominal malignancy. Many studies allowed a better understanding of prognostic factors and they permitted to adapt treatment according to a risk stratification approach.

Aim: To assess the most significant factors influencing the survival of patients presenting nephroblastoma.

Methods: We conducted a retrospective study over a 10-year period between 2001 and 2010 including 42 nephrectomy specimens, assessed in the pathology department of Salah Azaiz Institute, from all children diagnosed with nephroblastoma. The tumors were subdivided into histological subtypes and histological risk groups according to the SIOP-2001 classification. Statistical analyses were performed using the Kaplan-Meir and the Cox regression methods.

Results: The median age was 38 months. The mixed type was the most common (40% of cases). The tumors were subdivided into intermediate histological risk group (81%) and high risk group (14%). The tumors were classified as stage I (38%), stage II (24%), stage III (9%), stage IV (17%) and stage V (12%). The four-year survival rate was 83% and the event free survival rate was 85%. Age, laterality, histological risk group, tumor volume, blastema volume, stage, capsular rupture and incomplete resection had a significant impact on survival. Predictive factors of relapse were: laterality, tumor volume, blastema volume, histological risk group, stage, capsular rupture and incomplete resection.

Conclusion: Histological type and stage were identified as the most important prognostic factors in nephroblastoma. Further large studies are needed to establish the impact of absolute blastemal volume.
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March 2018

A rare case of a brain metastasis in a 4year old child.

Ann Pathol 2019 02 2;39(1):14-17. Epub 2018 Aug 2.

Pathology Department, Salah Azaiez Institute, Tunis, Tunisia. Electronic address:

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http://dx.doi.org/10.1016/j.annpat.2018.06.004DOI Listing
February 2019

Evaluation of tumor-free distance and depth of myometrial invasion as prognostic factors in endometrial cancer.

Mol Clin Oncol 2018 Jul 16;9(1):87-91. Epub 2018 May 16.

Pathology Department, Salah Azaïz Institution, 1006 Tunis, Tunisia.

The aim of the study was to investigate whether the tumor free distance (TFD), which is the distance in millimeters between the deepest point of invasion and the serosal surface, and absolute depth of invasion (DMI), the distance in millimeters between the endomyometrial junction and the deepest point of myometrial invasion, are useful in surgical staging and in predicting prognosis. The present study retrospectively analyzed 62 cases of endometrial carcinoma with complete surgical staging, carried out over a 4 and half-year period (January 2003 to June 2007). All surgicopathological findings including surgical stages, histological type and grade, myometrial invasion, lymphovascular space invasion, cervical and adnexal involvement, and lymph node metastasis were abstracted from medical records and pathological reports. Univariate and multivariate analyses were performed comparing TFD, DMI and the percentage of mypmetrial invasion (MI) with established prognostic factors. A total of 62 patients were included in the study. A total of 52 (84%) had endometrioid carcinomas and 31 patients (60%) had grade 1 cancer. The deepest MI was <50% in 32 patients (52%). Median DMI was 2.7 mm (range 0-15 mm). Median TFD was 3 mm (range 0-19 mm). There was lymphovascular space invasion (LVSI) in 11 patients (17.5%), cervical involvement in 11 patients (17.5%), extra-uterine extension in 9 cases (14%) and lymph node metastasis in 12 patients (22%). It was demonstrated that 50% MI was significantly associated with prognostic factors (cervical involvement, type 2 carcinomas and LVSI, and was a significant predictor of the 5-year overall survival rate and recurrence-free survival (P=0.05, P=0.01). No significant association was observed between DMI and TFD with clinicopathological parameters and survival rates. The importance of DMI in predicting recurrence of disease was observed to be highest in terms of sensitivity and specificity. The cut-off value with the highest sensitivity and specificity crossing the receive operating characteristic curve was calculated to be 3 mm for DMI and 2.5 mm for TFD. The results indicate that DMI is a superior predictive factor of recurrence of the disease compared with TFD. However, further studies are required in order to prove the prognostic usefulness of these parameters and then to improve management of endometrial cancer.
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http://dx.doi.org/10.3892/mco.2018.1629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995060PMC
July 2018

Increased plasmatic soluble HLA-G levels in endometrial cancer.

Mol Immunol 2018 07 3;99:82-86. Epub 2018 May 3.

Laboratoire Microorganismes et Biomolécules Actives, Département de Biologie, Faculté des Sciences de Tunis, Université Tunis El Manar, 2092, Tunis, Tunisia. Electronic address:

Human Leukocyte Antigen-G (HLA-G) is known as an immune suppressive molecule; it interacts with several immune cells and inhibits their functions. HLA-G molecule is highly represented in pathological conditions including malignant transformation. To the best of our knowledge this is the first study that focuses on the expression of soluble HLA-G (sHLA-G) in endometrial cancer (EC). We aimed at exploring sHLA-G plasma levels and its prognostic value in EC. We examined total sHLA-G expression as well as the sHLA-G1 and HLA-G5 isoforms expression in plasma samples from 40 patients with EC and 45 healthy controls by a specific sandwich ELISA. Immunoprecipitation and Coomassie blue staining were performed to explore the presence of plasmatic sHLA-G monomers and dimers. sHLA-G plasma level was significantly enhanced in patients with EC compared to healthy controls (p = 0.028). Additionally, HLA-G5 molecules were highly represented than sHLA-G1 molecules in EC, at the borderline of significance (p = 0.061). Interestingly, sHLA-G has been shown to be increased in early stages (Stages I and II) as well as in high grade EC (Grade 3) that is associated with rapid spread of the disease (p = 0.057). sHLA-G EC plasma were majorly in monomeric form (75%). Clinically, all the HLA-G dimers were detected in early stages and in high grade of EC. Our data strengthen the implication of HLA-G molecules in EC etiology and especially in progression.
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http://dx.doi.org/10.1016/j.molimm.2018.04.007DOI Listing
July 2018

Clinicopathologic significance of HLA-G and HLA-E molecules in Tunisian patients with ovarian carcinoma.

Hum Immunol 2018 Jun 2;79(6):463-470. Epub 2018 Mar 2.

Laboratory Microorganisms and Active Biomolecules, Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, Tunisia. Electronic address:

Background: The human leukocyte antigen (HLA)-G and HLA-E, non classical HLA class I molecules, have been highly implicated in immune tolerance. HLA-G and HLA-E molecules were proposed as putative markers of several advanced cancers. As a step towards a better understanding of ovarian carcinoma, we evaluated the expression of both HLA-G and HLA-E molecules and explored their prognostic implication.

Methods: HLA-G and HLA-E expression were studied by immunohistochemistry on ovarian carcinoma tissues. This expression was semi-quantitatively scored into four expression groups and correlated to clinicopathological parameters and patients' survival.

Results: HLA-G and HLA-E have been found to be highly expressed in ovarian carcinoma tissues (Respectively, 72.4% and 96.8%). They are frequently co-expressed. Univariate and multivariate analysis revealed that a positive HLA-G expression status in tumor tissue is a promising candidate parameter to predict disease recurrence in addition to the disease status in Tunisian patients with ovarian carcinoma. Moreover, the elevated HLA-E expression was associated with serous ovarian carcinoma subtype as well as with advanced stages of ovarian carcinoma.

Conclusion: HLA-G and HLA-E are highly represented in ovarian carcinoma suggesting a potential association with progressive disease mechanism. HLA-G and HLA-E molecules might be new candidates' markers for ovarian carcinoma progression.
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http://dx.doi.org/10.1016/j.humimm.2018.02.012DOI Listing
June 2018

[Endometrial carcinoma: An histopathological and histoprognotic study about 62 patients in a center in the Tunisian north].

Ann Pathol 2018 Apr 15;38(2):85-91. Epub 2018 Feb 15.

Departement of Pathology, Institut Salah-Azaiz, 1006 Tunis, Tunisie.

Endometrial cancer is the most prevalent genital tract cancer in occident and the third most common cancer among women in Tunisia. It is dominated by carcinoma. The identification of prognostic factors allows a better understanding of its outcome and guides its therapeutic approach. We propose to describe the clinicopathological features and identify the histoprognostic factors of this cancer. It is a retrospective analysis of a series of 62 total hysterectomy specimens with bilateral salpingo-oophorectomy from women with primary carcinoma of the endometrium, colligated in Anatomy Laboratory and Pathology Salah Azaiz Institute of Tunis over a period of 5 years, from January 2003 to December 2007. The median age was 60 years. At the time of diagnosis, 25% of patients were nulliparous and 86% were menopaused. The endometrioid adenocarcinoma was the most common, accounting for 84% of cases (5% of them were grade 3). A myometrial invasion superior or equal to 50% was observed in 40% of cases. 42% of cases were classified as stage IA, 14% in stage IB, 16% in stage II, 18% stage III and 10% in stage IV. 22% of patients had nodal involvement. Overall survival at 5 years was 81%. In multivariate analysis, stage IV, nodal involvement and brachytherapy have influenced this rate. Event-free survival at 5 years was 71%. It was directly related to stage and nodal involvement. Stage, histological type, tumor grade, invasion of more than half of the myometrium and lymph node involvement were the most important adverse prognostic factors, dictating an appropriate management of these tumors.
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http://dx.doi.org/10.1016/j.annpat.2017.12.001DOI Listing
April 2018

[Neu-Laxova syndrome: Three case reports and a review of the literature].

Ann Pathol 2016 Aug 27;36(4):235-44. Epub 2016 Jul 27.

Service d'embryo-fœtopathologie, centre de maternité et de néonatologie, 1007 Tunis, Tunisie.

Introduction: The Neu-Laxova syndrome (NLS) is a rare autosomal recessive and early lethal disorder. It is characterized by severe intra-uterine growth retardation, abnormal facial features, ichthyotic skin lesions and severe central nervous system malformations, especially microlissencephaly. Others characteristic features associated with fetal hypokinesia sequence, including arthrogryposis, subcutaneous edema and pulmonary hypoplasia, are frequently reported in NLS.

Patients And Methods: The clinicopathological characteristics of NLS are described in three cases with striking prenatal diagnostic findings and detailed post-mortem examinations. A review of the literature is undertaken with a focus on molecular basis.

Results: We present three new patients with NLS: one stillbirth male and two female newborns, delivered at 29, 35 and 40 weeks of gestational age, respectively. Characteristic ultrasound findings included hydramnios, severe intra-uterine growth restriction, craniofacial and cental nervous system anomalies. The cytogenetic study, performed in one case, was normal. The post-mortem examination revealed characteristic abnormalities in all three cases, that allowed to make a prompt diagnosis of the NLS. Data from these patients suggest that the NLS represents a heterogeneous phenotype. This feature has been highlighted in the literature.

Conclusion: The SNL is a lethal developmental disorder characterized by phenotypic heterogeneity with striking neurological defects. It is underpinned by genetic heterogeneity. It can be caused by mutations in all three genes involved in de novo L-serine biosynthesis: PHGDH, PSAT1 and PSPH. Hence, the NLS constitutes the most severe end of already known human disease, i.e. serine-deficiency disorder.
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http://dx.doi.org/10.1016/j.annpat.2016.04.004DOI Listing
August 2016

[An exceptional endocervical nodule].

Ann Pathol 2015 Oct 12;35(5):454-5. Epub 2015 Sep 12.

Service d'anatomie et de cytologie pathologiques, institut Salah Azaiz, hôpital militaire, Montfleury, 1008 Tunis, Tunisie.

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http://dx.doi.org/10.1016/j.annpat.2015.05.005DOI Listing
October 2015

Orbital tumor revealing a systemic sarcoidosis.

Acta Med Iran 2015 ;53(3):195-7

Department of Pathology, Salah Azaeiz Institute, Bab Saadoun, 1006 Tunis, Tunisia.

Ocular involvement is seen in approximately 25% of patients with sarcoidosis. Uveitis is the most common ocular manifestation, but sarcoidosis may involve any part of the eye. Orbital manifestations of sarcoidosis are uncommon with few series in the literature. A 65-year-old woman presented with redness of the right eye and painless, unilateral eyelid swelling. Orbital scanning revealed mass infiltrating the soft tissue of the inferior right orbital quadrant. Biopsy results showed nodular, noncaseating granulomas consistent with sarcoidosis. The complete systemic workup revealed systemic manifestations of sarcoidosis at the time of examination with hilar and mediastinal lymphadenopathies noted on CT scan. The orbital surgical treatment was followed by systemic prednisone therapy with good response. Although rare, orbital sarcoidosis must be considered in the evaluation of orbital tumors in elderly patients. A search for systemic findings should be undertaken and appropriate therapy should be instituted.
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September 2015

[Esthesioneuroblastoma].

Bull Cancer 2012 Dec;99(12):1197-207

Centre hospitalier universitaire Habib Bourguiba, service de radiothérapie carcinologique, route el Aïn Km 0.5, 3029 Sfax, Tunisie.

Esthesioneuroblastoma is an uncommon malignancy originating from olfactive epithelium. Men are more frequently affected than women. Nasal symptoms are the most common revealing signs. Immunohistochemistry helps diagnosis. There is no randomized trial evaluating treatment due to the low incidence of this tumor. Radiotherapy and surgery are the standard of care. Radiotherapy is benefic even in early stage disease. Chemotherapy is indicated in case of locally advanced or metastatic disease.
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http://dx.doi.org/10.1684/bdc.2012.1642DOI Listing
December 2012

Pure seminoma: a review and update.

Radiat Oncol 2011 Aug 8;6:90. Epub 2011 Aug 8.

Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Bugnon 46, CH-1011 Lausanne, Switzerland.

Pure seminoma is a rare pathology of the young adult, often discovered in the early stages. Its prognosis is generally excellent and many therapeutic options are available, especially in stage I tumors. High cure rates can be achieved in several ways: standard treatment with radiotherapy is challenged by surveillance and chemotherapy. Toxicity issues and the patients' preferences should be considered when management decisions are made. This paper describes firstly the management of primary seminoma and its nodal involvement and, secondly, the various therapeutic options according to stage.
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http://dx.doi.org/10.1186/1748-717X-6-90DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163197PMC
August 2011
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