Small Intestine Gastrointestinal Clear Cell Sarcoma: A Case Report and Review of the Literature.

Gastrointestinal clear cell sarcoma (GICCS)/malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare form of cancer with aggressive clinical behavior. It has distinct pathological, immunohistochemical, ultrastructural, and molecular features. Herein, we present the case of a 20-year-old woman with no notable medical history who presented to the outpatient department with complaints of abdominal pain and vomiting. Symptoms had been evolving for 3 months. The physical examination revealed slight abdominal tenderness and melena. Biological investigations revealed iron-deficiency anemia. The upper and lower endoscopies showed no abnormalities. Magnetic resonance enterography revealed small bowel wall thickening of 15 mm × 2 mm. Exploratory laparotomy revealed an ileal mass with mesenteric lymphadenopathy. A wide resection of the mass was then performed. The final pathological report confirmed the diagnosis of small bowel GICCS/GNET. After 11 months of follow-up, the patient presented with mesenteric lymph node metastases.

Olfactory cleft mass as the first presentation of asymptomatic metastatic renal cell carcinoma: A case report and review of the literature.

INTRODUCTION AND IMPORTANCE: Renal cell carcinoma metastasis in the sinonasal cavities is rare. They account for less than 1 % of all metastases of these renal cancers. CASE PRESENTATION: We report the case of a patient with an unremarkable pathological history, who consulted for recurrent right epistaxis. Nasal endoscopy revealed a reddish mass located medial to the right middle turbinate. Computed tomography and magnetic resonance imaging showed a lesion located at the level of the olfactory cleft. The patient had a complete removal of the mass and the anatomopathological examination concluded to a metastasis of a clear cell carcinoma of renal origin. Taking into account these results, a thoraco-abdomino-pelvic CT scan was performed and it discovered a left renal tumor. CLINICAL DISCUSSION: The most frequent functional sign of Renal cell carcinoma metastases is epistaxis. This is explained by the rich vascularity of these metastases. The imaging data are not specific and do not allow differentiation between primary tumor and metastasis. The definitive diagnosis can be confirmed only by histologic examination. CONCLUSION: Faced with any hypervascularized tumor of the nasal cavity, the ENT physician must evoke a metastasis of a renal cancer, even in the absence of history and symptoms evoking this cancer.

Indoleamine 2,3-dioxygenase gene expression and kynurenine to tryptophan ratio correlation with nasopharyngeal carcinoma progression and survival.

INTRODUCTION: Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive tryptophan-depleting enzyme expressed in nasopharyngeal carcinoma (NPC) tissue. However, IDO has not been reported in the peripheral blood of NPC patients. The aim of this study was to analyze, IDO1 and IDO2 messenger RNA (mRNA) expression, the kynurenine (Kyn) and tryptophan (Trp) plasma levels, their clinical values and their relationship with cytokine levels in NPC. METHODS: We evaluated IDO1 and IDO2 mRNA expression in peripheral blood mononuclear cells (PBMC) by quantitative real-time PCR, plasma Trp and Kyn levels by HPLC, and cytokine levels by ELISA in 75 NPC patients and 51 healthy controls. RESULTS: Compared to controls, IDO1 mRNA expression was significantly upregulated and IDO2 mRNA expression was significantly downregulated in PBMC of patients. Also compared to controls, plasma Kyn levels and Kyn/Trp ratio were significantly higher in patients. At the time of diagnosis, the plasma Kyn/Trp ratio was associated with advanced cancer status and was an independent prognostic factor for worse disease-specific survival. According to cancer stages, IDO1 mRNA expression was positively correlated with plasma Kyn/Trp ratio in patients with earlier stages (I-II-III) but negatively correlated in patients with the late-stage cancer (IV). Tumor necrosis factor-α, interleukin (IL)-6 and IL-10 levels were significantly higher in patients compared to controls. Moreover, and despite treatment, patients simultaneously carrying high plasma Kyn/Trp ratio and high plasma IL-6 and IL-10 levels at diagnosis died approximately 1 year after first diagnosis. CONCLUSION: Measuring blood IDO mRNA expression and Kyn/Trp ratio at diagnosis could be a potential marker to evaluate NPC progression and predict survival outcome.

2,4-Dichlorophenoxyacetic acid (2,4-D) affects DNA integrity and retina structure in zebrafish larvae.

Monitoring the potential risk of herbicides in non-target organisms is a crucial issue for environmental safety. 2,4-D is an herbicide of high environmental relevance that has been shown to exert toxic effects to soil and aquatic biota. In the present study, we investigated the possible genotoxic and retinal development effects of 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide in early life stages zebrafish (Danio rerio). Genotoxicity was evaluated by measuring DNA damage using the comet assay and also by the mRNA expression of genes implicated in apoptosis and/or DNA repair. Retinal development toxicity was evaluated with histological approach. The results obtained revealed that 2,4-D alters DNA integrity of zebrafish larvae. Moreover, transcriptomic data showed a significant induction of p-53 and casp-3 genes and a significant decrease of lig-4 in larvae exposed to the highest tested concentration of 2,4-D (0.8 mg/L). This suggested that p-53 gene regulates the process of DNA repair and apoptosis with increased levels of 2,4-D. The histopathological analysis revealed that early exposure to 2,4-D damaged the structure of larvae retina. Overall, this study is the first to report the DNA damage, casp-3, lig-4 and p-53 regulation, as well as the ocular developmental toxicity in zebrafish larvae at environmentally relevant concentrations of 2,4-D herbicide.

Human glutathione peroxidase codon 198 variant increases nasopharyngeal carcinoma risk and progression.

PURPOSE: Glutathione peroxidase 1 (GPx-1) is a selenium-dependent detoxifying enzyme involved in the protection of cells against oxidative damage. Some genetic association studies reported significant associations between GPx-1 Pro198Leu variant and carcinogenesis across different populations; however, the impact of this variant on nasopharyngeal carcinoma (NPC) has not been explored. Therefore, the present study was planned to evaluate the potential involvement of the GPx-1 Pro198Leu variant and plasma GPx activity in the risk of developing NPC in a Tunisian population. METHODS: The GPx-1 Pro198Leu genotype was determined in 327 NPC patients and 150 healthy controls by the RFLP-PCR analysis. The correlation between the GPx-1 variant and the clinicopathological parameters was examined. GPx activity was assessed in the plasma of 119 NPC patients and 58 healthy control subjects and according to GPx-1 genotypes and clinicopathological characteristics of NPC patients. RESULTS: A significant association was found between GPx-1 Pro198Leu variant and NPC risk in a Tunisian population. The allelic frequencies of Pro and Leu alleles were 32% versus 68% and 41% versus 59% in NPC cases and controls, respectively. Thus, the minor 198 Leu allele increased significantly in NPC patients and appeared as a potential risk factor for NPC occurrence (OR = 1.48, CI 95% = 1.14-1.91, p = 0.002). The plasma GPx activity was significantly higher in NPC patients than in controls (p = 0.03). According to the clinicopathological characteristics of NPC patients, GPx activity decreased significantly in patients with lymph node metastasis (p = 0.004). CONCLUSION: This is the first study showing a strong association between GPx-1 Pro198Leu genetic variant and NPC risk. GPx-1 Pro198Leu variant increased the development of regional lymph node metastasis. Plasma GPx activity was higher in NPC patients. Thus, GPx-1 gene could be considered as a determinant factor influencing NPC risk and progression.

An unusual presentation revealing Peutz-Jeghers syndrome in adult.

INTRODUCTION: Peutz-Jeghers syndrome (PJS) is a rare hereditary disease characterized by hyperpigmentation on the lips and oral cavity and gastrointestinal hamartomatous polyps. The most common complications in PJS patients are bleeding, bowel obstruction and intussusception. PRESENTATION OF CASE: We hereby report a case of a 33-year-old female, without a family history of the disease, who presented to the emergency room with acute abdominal pain, bloating and not passing gas. On abdominal examination, upper abdominal and periumbilical tenderness was found. Computed tomography (CT) of the abdomen demonstrated suspected ascending colon intussusception. The patient underwent a mid-line laparotomy that showed an ileocolic intussusception. Reduction of this intussusception was successfully done with resection of the affected segment that showed presence of two pedunculated polyps. The specimen was sent thereafter to our department for histopathological evaluation, which confirmed the diagnosis of hamartomatous Peutz-Jeghers polyps with no malignancy. Afterwards, the patient was carefully reexamined and the physical examination revealed multiple pigmented spots on the face and lips. Thus, the diagnosis of Peutz-Jeghers syndrome was made. DISCUSSION: PJS is a rare autosomal dominant disorder that often remain undiagnosed for many years. Acute complications such as intestinal obstruction secondary to intussusception is one of infrequent revealing symptoms. CONCLUSION: Early identification, in patients with PJS and family members, as well as close cancer surveillance can improve certainly prognosis in these individuals.

Prevalence of antibodies against a cyclic peptide mimicking the FG loop of the human papillomavirus type 16 capsid among Tunisian women.

BACKGROUND: In the past decade, cervical cancer has gone from being the second to the fourth most common cancer in women worldwide, but remains the second most common in developing countries. This cancer is most commonly caused by high-risk types of human papillomavirus (HPV), mainly type 16 (HPV16), which are sexually transmitted. This study aimed to investigate the usefulness of a cyclic synthetic peptide designed from the major L1 capsid protein of HPV16 for detecting anti-HPV16 antibodies. METHODS: We designed and synthetized a peptide that corresponds to the full sequence of the surface-exposed FG loop. We tested the antigenicity of the linear and the cyclic peptides against HPV16 L1 monoclonal antibodies. We used ELISA to detect anti-peptide antibodies in sera and cervical secretions of 179 Tunisian women, and we applied polymerase chain reaction and direct sequencing methods to detect and genotype HPV DNA. RESULTS: Both the linear and the cyclic peptides were recognized by the same neutralizing monoclonal antibodies, but the cyclic peptide was more reactive with human sera. The prevalence of the anti-peptide antibodies in sera was higher in women with low-grade squamous intraepithelial lesions (LGSIL) than in women with high-grade squamous intraepithelial lesions (HGSIL) (44% and 15%, respectively). This contrasts with HPV16 DNA prevalence. Compared to women from the general population, systemic IgG prevalence was significantly higher among sex workers (25%; P = 0.002) and women with LGSIL (44%; P = 0.001). In addition, systemic IgA and cervical IgG prevalence was higher among sex workers only (P = 0.002 and P = 0.001, respectively). We did not observe anti-peptide IgG antibodies in women with a current HPV16 infection. CONCLUSION: Anti-peptide IgG in sera or in cervical secretions could be markers of an effective natural immunization against HPV16. This may open novel perspectives for monitoring vaccinated women and for the design of synthetic peptide-based vaccines.

Spontaneous Rupture of a Hepatic Cavernous Hemangioma: A Rare Case of Sudden Unexpected Death.

Cavernous hemangiomas represent the most common benign tumors affecting the liver. They are more often asymptomatic and usually diagnosed through radiological examinations performed for other reasons. When there are symptomatic, they may cause digestive disorders such as abdominal pain, nausea, vomiting, or a palpable mass. Sudden death may occur as a result of rupture and bleeding. Spontaneous rupture of cavernous hepatic hemangioma is a rare complication, but the mortality rate is high. We report a rare case of sudden unexpected death of a 46-year-old woman due to a spontaneous rupture of a giant hepatic cavernous hemangioma discovered at autopsy.

Sudden death due to left ventricular thrombosis: A report of two autopsy cases.

PURPOSE: In this paper, we report two rare cases of sudden death due to giant left ventricular thrombus revealed at autopsy and we discuss the manner and the cause of death. RESULTS: Cases presentation: The two cases reported are about two men aged 55 and 53 years respectively. In the two cases, no past cardiac history was found. Prior to the onset of complications and subsequent death, both patients presented to the emergency department with progressing asthenia, faintness and shortness of breath, were treated symptomatically. At autopsy, atherosclerosis of coronary arteries was found. In the first case, death was attributed to thrombosis of the pseudoaneurysm. In the second case, it was due to thrombosis complicating a myocardial infarction. The mechanism of death in the first case was explained by the hemodynamic shock caused by a total left ventricular pseudoaneurysm thrombosis secondary to old myocardial infraction. In the second case, death was the consequence of a cardiogenic shock secondary to thrombosis of the cardiac pseudoaneurysm complicating a myocardial infraction. CONCLUSION: Complications of myocardial infarction represent frequent causes of adult sudden death. Left ventricular thrombosis is a complication that is often fatal and its discovery during an autopsy remains rare. The first-line doctor must take these types of complications into consideration in order to detect them and thus ensure timely management.

Contribution of Nitric oxide synthase 3 genetic variants to nasopharyngeal carcinoma risk and progression in a Tunisian population.

PURPOSE: We conduct this study to evaluate the clinical and functional impact of Nitric Oxide Synthase 3 (NOS3) T-786C and G894T genetic variants on nasopharyngeal carcinoma (NPC) risk and progression in a Tunisian population. METHODS: 259 NPC patients and 169 healthy controls were enrolled into our case-control study. Blood samples were genotyped by the RFLP-PCR analysis. The levels of Nitric oxide (NO) were measured by a colorimetric assay kit in the plasma of NPC patients, healthy controls and according to NOS3 genotypes. The correlation between the NOS3 variants and the clinicopathological parameters was examined. RESULTS: We found no linkage disequilibrium between NOS3 T-786C and G894T variants. These results showed that NOS3 variants were genetically independent. In contrast to NOS3 T-786C, a significant association was found between NOS3 G894T polymorphism and NPC risk. The 894T allele decreased significantly in NPC patients and appeared as protective factor (OR = 0.65, CI 95%= 0.48-0.88, p = 0.006). NPC patients had significantly higher levels of plasma NO as compared to healthy controls (p = 0.0011). The T-786C mutation reduced the levels of plasma NO and decreased risk of lymph node metastasis in NPC patients (OR = 0.64, 95% CI = 0.43-0.96; p = 0.03). In contrast, NOS3 G894T polymorphism had no effects neither on NO plasma levels nor clinical parameters. CONCLUSIONS: This is the first study to associate NPC with significantly higher levels of plasma NO. NOS3-derived NO could play key roles in NPC pathogenesis. NOS3 variants differently contribute to NPC risk and progression in a Tunisian population. NOS3 G894T was associated with NPC risk. NOS3 T-786C decreased the levels of plasma NO and reduced the development of regional lymph node metastasis.

Protective potential of Opuntia microdasys flower decoction on fructose-alloxan-induced diabetic rats on kidney and pancreas: chemical and immunohistochemical analyses.

Diabetes is a serious condition that is linked to the development of oxidative stress causing among many other effects, kidney failure and pancreatic disorders. However, traditional plant-based remedies can be considered an alternative to diabetes healing. In this context, this study was oriented towards evaluating the protective effect of the flowers of Opuntia microdasys Lehm. collected in Tunisia at a biochemical and histological level on kidneys and pancreas of a type 2 diabetic rats. Renal and pancreatic toxicities were induced in diabetic male Wistar rats by fructose alloxan. Diabetic rats were treated with an extract obtained from flowers collected at post-flowering stage (OFP) (100 and 200 mg kg-1 bw) and metformin (100 mg kg-1 bw) for 28 days. Oral administration of OFP at 200 mg kg-1 bw showed significant reduction of the uric acid, urea, creatinine, amylase, lipase, and glycated hemoglobin (HbAlc). The levels of SOD, CAT, and GPx were increased, while protein carbonyls and lipid peroxidation TBARS levels were reduced in the kidney and pancreas. The altered kidney and pancreas histology were restored in rats treated with OFP. Thus, the present study demonstrated that OFP has antihyperglycemic activity in fructose-alloxan-induced diabetic rats.

E-cadherin genetic variants predict survival outcome in breast cancer patients.

BACKGROUND: E-cadherin is a major component of adherens junctions that regulates cell shape and maintains tissue integrity. A complete loss or any decrease in cell surface expression of E-cadherin will interfere with the cell-to-cell junctions' strength and leads to cell detachment and escape from the primary tumor site. In this prospective study, three functional single nucleotide polymorphisms (-347G/GA, rs5030625; -160C/A, rs16260; +54C/T, rs1801026), were found to modulate E-cadherin expression. METHODS: 577 DNA samples from breast cancer (BC) cases were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: We detected no significant correlations between each polymorphism and the clinical parameters of the patients whereas the GACC haplotype was significantly associated with low SBR grading. Overall survival analysis showed that both -347G/G and +54C/C wild (wt) genotypes had a significantly worse effect compared to the other genotypes (non-wt). Moreover, carrying simultaneously both the -347 and +54 wt genotypes confers a significantly higher risk of death. However, with metastatic recurrence, the death-rate was null in patients carrying the non-wt genotypes, and attained 37% in those carrying the wt genotype. A multivariate analysis showed that these two polymorphisms are independent prognostic factors for overall survival in BC patients. CONCLUSIONS: Our results support the fact that E-cadherin genetic variants control disease severity and progression and could be a marker of disease outcome. These findings could be useful in selecting patients that should be monitored differently.

Prognostic value of indoleamine 2,3-dioxygenase activity and expression in nasopharyngeal carcinoma.

Indoleamine 2,3-dioxygenase (IDO) is an enzyme with an immunosuppressive effect whose function is diverted by tumor cells to counteract immune cell functions, inducing immune escape of tumor cells. The aim of this study was to investigate the clinical significance of IDO in nasopharyngeal carcinoma (NPC). Compared to controls, NPC patients' plasma IDO activity was significantly higher, especially among patients with metastatic cancer (p=0.005). The immunohistochemical analysis revealed that high IDO expression was observed in 74% of NPC tissues and the epithelial IDO expression was inversely correlated to T-cell infiltration. Kaplan-Meier survival analysis showed that whatever the localization, intratumoral or stromal, patients with a high IDO expression and low T-cell infiltration have significantly lower survival rates. Moreover, in multivariate analysis, intratumoral and stromal IDO expression were found to be independent prognostic factors for disease-free survival (p=0.016; HR: 3.52) and overall survival (p=0.015; HR: 4.76) respectively. Our findings provide evidence that IDO is involved in tumor immune evasion of NPC, suggesting that it could be a relevant therapeutic target for NPC.

Assessment of MYCN amplification status in Tunisian neuroblastoma: CISH and MLPA combining approach.

BACKGROUND: Neuroblastoma (NB) shows a complex combination of genetic aberrations. Some of them represent poor genetic prognosis factors that require specific and intensive chemotherapy. MYCN amplification consists of the major bad outcome prognostic factor, it is indeed frequently observed in aggressive neuroblastomas. To date different methods are used for MYCN status detection. OBJECTIVES: The primary aim of our study was to provide a critical assessment of MYCN status using 2 molecular techniques CISH and MLPA. We also focused on the correlation between neuroblastoma genetic markers and patient's clinical course among 15 Tunisian patients. METHODS: we developed a descriptive study that includes 15 pediatric Tunisian patients referred to our laboratory from 2004 to 2011. We reported the analysis of fresh and FFPE NB tumors tissues. RESULTS: No significant correlation was found between COG grade and patients overall survival. Assessment of NMYC gene copy number by kappa statistic test revealed high concordance between CISH and MLPA tests (kappa coefficient = 0.02). CONCLUSION: Despite misdiagnosing of MYCN status fewer than 5 copies, MLPA remains an effective molecular technique that enables a large panel of genomic aberrations screening. Thus combining CISH and MLPA is an effective molecular approach adopted in our laboratory. Our results allow pediatric oncologists to set up the first Neuroblastoma therapeutic strategy based on molecular markers in Tunisia.

Partial KCNQ1OT1 hypomethylation: A disguised familial Beckwith-Wiedemann syndrome as a sporadic adrenocortical tumor.

Beckwith-Wiedemann syndrome has a wide spectrum of complications such as embryonal tumors, namely adrenocortical tumor. Tumor predisposition is one of the most challenging manifestations of this syndrome. A 45-day old female with a family history of adrenocortical tumor presented with adrenocortical tumor. The case raised suspicion of a hereditary Beckwith-Wiedemann syndrome, therefore molecular analysis was undertaken. The results revealed partial KCNQ1OT1 hypomethylation in the infant's blood DNA which was associated with a complete loss of methylation in the infant's adrenocortical tumor tissue. It is unique for familial Beckwith-Wiedemann syndrome caused by KCNQ1OT1 partial hypomethylation to manifest solely through adrenocortical tumor. Incomplete penetrance and specific tissue mosaicism could provide explanations to this novel hereditary Beckwith-Wiedemann syndrome presentation.

Oxidative damage and alterations in antioxidant enzyme activities in the kidneys of rat exposed to trichloroacetic acid: protective role of date palm fruit

In this study, we investigated the antioxidant and protective properties of date fruit aqueous extract (DFAE) on trichloroacetic acid (TCA)-induced nephrotoxicity in rat. Oral administration of TCA as drinking water (0.5 and 2 g/L) daily for 2 months caused nephrotoxicity as evident by elevated levels of plasma creatinine, urea, and uric acid. Activity of antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx), was decreased, whereas superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were increased along with histopathological injuries. The oral administration of DFAE (4 mL/kg/day) to TCA-treated groups proved some significant correction by increasing the antioxidant activity of the CAT and GPx enzymes and normalizing the SOD activity and the MDA level (p < 0.05). It also protected kidney's histology and normalized the functions of this organ. It could be concluded that DFAE has a protective role against TCA-induced oxidative stress in rat, thereby protecting the renal tissue from TCA-induced damage