Impact of the COVID-19 pandemic on breast cancer pathological stage at diagnosis in Tunisian patients.

BACKGROUND: Breast cancer (BC) patients' diagnosis and management was affected by a global reorganization after the Coronavirus disease 2019 (COVID-19). Our study aimed to assess the impact of the pandemic on the pathological stage of newly diagnosed patients with BC compared to pre-pandemic and to identify predictive factors of tumor advanced stage. METHODS: Pathological records of all consecutive newly operated BC patients between March 2020 and December 2021 were reviewed retrospectively. Clinical and pathological prognostic factors of BC were collected and compared between pre-pandemic and pandemic periods. Then, predictive factors of tumor advanced stage were identified. RESULTS: Of the 225 cases included in the analysis, 98.7% were females and 1.3% were males. The median time from first histological diagnosis to first surgical treatment was enlarged by 42 days with a significant difference between the two periods (p = 0.002). Newly diagnosed BC patients during the COVID-19 pandemic were operated at a more advanced stage (54.1% vs 36.2%, p = 0.007), had a greater lymphovascular invasion (p = 0.002), lymph node metastasis (p = 0.015) and are more commonly of IBC NST histological type (p = 0.005). Moreover, multivariate analyses showed that the pandemic period (AOR = 2.28; p = 0.016) and the lympho-vascular invasion (p < 0.001) were independently associated with advanced stage of tumors. CONCLUSION: Our findings proved an increase in alarming rates of advanced stage BC associated with the COVID-19 crisis. These findings support recommendations for a quick restoration of BC screening at full capacity, with adequate prioritization strategies to mitigate harm.

The effects of prolonged stress exposure on the brain of rats and insights to understand the impact of work-related stress on caregivers.

Introduction: Stress exposure is a significant concern in the healthcare sector. This animal model study aims to reproduce caregivers' working conditions and determine their impact on the brain. Method: Twenty-four healthy male rats of the Wistar strain were divided into four groups. Three groups were submitted each to one stressor for 21 days, while the fourth group was used as a control. Stressors were food and water deprivation (FW), permanent illumination (PI), and forced swimming (FS). At the end of the experiment, rats were euthanized, and stress biomarkers, biological parameters, and DNA damage were measured. Results: Prooxidant biomarker rates increased in the different groups (+50 to +75%) compared to the control (p < 0.0001). Urinary corticosterone rates increased in all stressed animals, mainly in the PI group, with changes of up to +50% compared to the control group. Acetylcholinesterase levels decreased to -50% (p < 0.0001 for the three exposed groups). Total ATPase, (Na+/K+)-ATPase, and Mg2+-ATPase activities decreased in all stressed groups. The percentage of brain cell congestion and apoptosis was 3% for the FW group (p < 0.0001), 2% for the PI group (p < 0.0001), and 4% for the FS group (p < 0.0001) compared to the control (0.8%). DNA damage was observed in all exposed groups. Finally, we noticed behavioral changes and a depression-like syndrome in all stressed rats. Conclusion: Stressful conditions such as the working environment of caregivers can trigger several pathophysiological processes leading to oxidative, neurochemical, and hypothalamic-pituitary-adrenal disorders. These changes can progress to cell damage and apoptosis in the brain and trigger psychological and physical disorders.

Mitigation of Hepatic Impairment with Polysaccharides from Red Alga Albidum corallinum Supplementation through Promoting the Lipid Profile and Liver Homeostasis in Tebuconazole-Exposed Rats.

Sulfated polysaccharides from seaweed are highly active natural substances with valuable applications. In the present paper, attempts have been made to discuss the physicochemical and structural features of polysaccharides isolated from red marine alga Alsidium corallinum (ACPs) and their protective effect in hepatic impairments induced by tebuconazole (TEB) in male adult rats. Structural features were determined using high-performance liquid chromatography, Fourier-transformed infrared, and solid-state 1H and 13C-Nuclear magnetic resonance analysis. ACPs are found to be hetero-sulfated-anionic polysaccharides that contain carbohydrates, sulfate groups, and uronic acids. In vitro biological activities suggested the effective antioxidant and antimicrobial capacities of ACPs. For antioxidant testing in vivo, the biochemical analysis and plasma profiles displayed that oral administration of ACPs could mitigate blood lipid indicators, including total cholesterol, triglyceride, low and high-density lipoprotein cholesterol, and bilirubin. Liver function indexes involving alanine aminotransferase and aspartate aminotransferase showed that ACPs possessed prominent antioxidant activities. Additionally, the intervention of ACPs potentially inhibited lipid peroxidation, protein oxidation, key enzymes of lipid metabolism (<0.001), and improved antioxidant status (<0.05). Histomorphological observation confirmed that ACPs intervention could partially repair liver injuries caused by TEB. The computational results showed that A. corallinum monosaccharides bound 1JIJ, 1HD2, and 1WL4 receptors with acceptable affinities, which, together with deep embedding and molecular interactions, support the antioxidant, antimicrobial, and hypolipidemic outlined effects in the in vitro and in vivo findings. Given their prominent antioxidant effects, ACPs are promising candidates for liver diseases and must be considered in pharmaceutical applications.

Warthin-like papillary thyroid carcinoma: a case report and comprehensive review of the literature.

Background: Papillary Thyroid Carcinoma (PTC) is the most frequent endocrine malignancy with a variety of histological presentations. Warthin-like Papillary Thyroid Carcinoma (WLPTC) is an uncommon neoplasm that is recognized as a distinct subtype of PTC in the WHO classification of thyroid tumors. In this report, we present a novel case of WLPTC in a female patient and provide an in-depth review of the available literature on its clinical, pathological, and therapeutic characteristics. Case presentation: A 27-year-old female patient was referred for neck swelling. Ultrasound showed two suspicious thyroid nodules leading to a thyroidectomy. She was diagnosed with intermediate-risk bifocal foci of classic PTC and WLPTC, arising from a background of chronic lymphocytic thyroiditis (CLT). This pT1b(m) N1b M0 malignancy was treated with adjuvant isotopic ablation and suppressive thyroxine therapy. The 1-year outcomes were favorable. Literature review: It covered articles published from 1995 to 2022, by searching PubMed and Google Scholar using specific terms. Out of 148 articles reviewed by two authors, 25 relevant articles were selected, including 13 case reports and 12 case series. The study included 150 cases of WLPTC. Data related to clinical presentation, imaging, histological features, management, and outcomes, were extracted. The mean age of diagnosis was 39 years, with a female predominance. The most common clinical presentation was neck swelling. Thyroid autoimmunity was positive in 71.6% of patients. Lymph node metastases were present in 28% of cases, with no reported distant metastases. Overall, the outcomes were favorable. Conclusion: WLPTC shares similar clinical and radiological presentations as classic PTC. The hallmark histological features of WLPTC are papillae lined with oncocytic tumor cells with papillary nuclear changes and lymphoid stroma. WLPTC is almost constantly associated with CLT. The management of WLPTC aligns with that of classic PTC with comparable stage and risk category, often resulting in favorable outcomes.

Inverted Follicular Keratosis: A Retrospective Study Over 10 Years.

Inverted follicular keratosis (IFK) is a rare benign tumour of the follicular infundibulum characterized by exo-endophytic growing. Generally, the diagnosis of IFK is histopathologically made because clinical differentiation from other lesions is difficult. We present a retrospective series with thirteen patients with histologically confirmed IFK to evaluate the epidemiological, clinical and histopathologic characteristics of IFK. The mean age of the patients at the time of the excision was 53 years with extremes ranging from 19 to 82 years. The sex ratio M/F was 3.3. The lesions affected the face in nine patients mainly the moustache, followed by the scalp in three cases and the arm in one case, and 92% of the localizations are sun-exposed. The diagnosis was never clinically evoked. The lesion had a pink colour in ten cases and was pigmented in two cases and hypopigmented in one case. More than half of the lesions (53%) had a keratotic centre. Histopathological examination showed endophytic intradermal proliferation of basaloid cells with a variable degree of squamoid differentiation. Horn cysts were present in all cases. According to our series, the IFK occurs predominantly in young men, in the face and more specifically in the moustache. Dermoscopy may suggest the diagnosis of the IFK. In fact, a histopathological examination is the gold standard for the diagnosis of the IFK and helps differentiate these benign tumours from possible malignant neoplasms.

The Prognostic Significance of CD10 Expression in Invasive Breast Carcinoma in Tunisian Patients.

BACKGROUND: Breast cancer is the first female cancer worldwide. Its prognosis depends mainly on pathological stage and histological grade. These classical prognostic factors are essential but may be insufficient to predict the outcome of the disease. Research focuses on identifying new prognostic factors such as CD10, which is a cell surface metalloproteinase. OBJECTIVE: This study aims to evaluate CD10 expression on stromal and tumor cells in invasive breast carcinomas and its correlations with other clinicopathological factors and survival. METHODS: A series of 100 cases of breast carcinoma of no special type diagnosed from 2009 to 2011, was investigated in this study. CD10 expression was detected by immunohistochemistry. Stromal CD10 expression (=10% stromal positivity was considered positive) and tumor cells expression (=1% stained carcinomatous cells) were noted. Statistical correlations were analyzed with different known prognostic parameters; survival analysis were performed using SPSS 22.0. RESULTS: Stromal CD10 expression was seen in 60% of the cases. It showed positive correlation with high tumor grade (p=0,012) and distant metastasis (p=0,02). CD10 expression on tumor cells was observed in 10% of the cases. It was associated with high tumor grade (p=0,009), hormone receptor negativity (estrogen receptor: p<0,0001), progesterone receptor: p=0,005), triplenegative phenotype (p=0,001), and Ki67 overexpression (p=0,046). Stromal CD10 expression was significantly associated to a shorter overall survival (p=0,029) and disease-free survival (p=0,05) in univariate analysis. CONCLUSION: Given these results, it can be concluded that CD10 expression predict an aggressive behavior of breast cancer. This marker can be introduced as a determinant prognostic factor.

Discordance in receptor status between primary and metastatic breast cancer and overall survival: A single-center analysis.

BACKGROUND: The tumor phenotype may change between primary and metastatic breast cancer. We compared the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2 in a series of primary breast carcinomas (PBC) with their metastatic relapses and analyzed the impact of any changes on survival. MATERIALS AND METHODS: It was a single-center retrospective study, collecting consecutive cases of metastatic breast carcinoma diagnosed in the pathology and medical oncology departments at Habib Bourguiba University Hospital in Sfax, Tunisia. An immunohistochemical study was used to assess ER, PR, and HER2 expression. Overall survival (OS) and post-metastasis survival (PMS) were evaluated using multivariable Cox regression analysis. RESULTS: Our study included 68 patients. ER and PR status changed in 29.4 % and 39.7 % of cases, respectively. Conversions were mainly from positive to negative status (22 % and 23.5 % for ER and PR, respectively). Differences in HER2 status were observed in 19.6 % of cases, with loss of overexpression in 6 patients (10.7 %). Adjuvant trastuzumab therapy and PBC molecular subtype (HR-, HER2+) were associated with HER2 status discordance (p = 0.02 and 0.03, respectively). On multivariable analysis, HR-negative conversion tumors were significantly associated with a worse OS (p = 0.042) and PMS (p < 0.001), compared to HR-concordant positive tumors. CONCLUSION: This study establishes that HR and HER2 status discordance between primary and metastatic breast carcinoma has a prognostic impact on patient outcome. Analyzing these receptors' status in all newly diagnosed cases of metastatic breast carcinoma is strongly recommended and would provide information for changing treatment strategies.

Immunohistochemical Overexpression of Cyclin D1 in Tunisian Invasive Breast Carcinoma Women.

BACKGROUND: Breast cancer represents the most frequent cancer and cause of death in women worldwide and in Tunisia. Cyclin D1 is a gene of cell cycle regulation. It represents a potential oncogene in invasive breast cancer; however; the results are conflicting. We performed a retrospective study aiming to analyze the prognostic impact of cyclin D1 expression in patients with invasive breast carcinoma of no special type and its relation with clinical-pathological features. METHODS: One hundred cases of invasive breast carcinoma of no special type diagnosed between 2009 and 2011 were included in this study. Immunohistochemical (IHC) staining was performed for cyclin D1 in all cases. Results were analyzed statistically. RESULTS: Cyclin D1 positivity was seen in 74 cases (74%), of which 32 cases (32%) showed strong immunoreactivity. Cyclin D1 staining was statistically significantly associated with estrogen receptor (ER) and progesterone receptor (PR) positivity (P<0.0001) and with low grade SBR (P=0.007). None of the clinical data and other pathological features had any association with cyclin D1 expression (P>0.05). Univariate analysis revealed that expression of cyclin D1 was not statistically associated with overall survival (OS) and disease-free survival (DFS) (P=0.459 and P=0.564, respectively). CONCLUSION: These results confirm that cyclin D1 overexpression can be employed as a beneficial prognostic marker and suggest that anti-cyclin D1 therapy may be efficient, especially for ER positive tumors.

Nasopharyngeal Metastasis from Breast Carcinoma: A Case Report and a Review of the Literature.

Metastasis to the nasopharynx is a rare clinical entity. Breast carcinoma is one of the primary tumors that can be responsible for a nasopharyngeal metastasis, which is an extremely rare occurrence. We report the case of a 50-year-old woman with a history of a confirmed breast carcinoma under chemotherapy who presented to our department with a unilateral hearing loss and tinnitus. Nasal endoscopy revealed a small bulging mass at the posterior wall of the nasopharynx. The biopsy of the lesion showed an infiltration of the nasopharyngeal mucosa by a mammary adenocarcinoma that was positive for estrogen and progesterone receptors and negative for human epidermal growth factor receptor 2. Computed tomography scan revealed a thickening of the nasopharyngeal mucosa, a pleural and pericardial effusion and diffused secondary bone lesions. The patient received chemotherapy. Control revealed a partial regression of the nasopharyngeal mass. The patient is still under chemotherapy.

Papillary thyroid carcinoma associated with glioblastoma in a neurofibromatosis 1 patient: An unusual and rare combination of multiple primary malignancies.

Introduction: and importance: Papillary Thyroid carcinoma (PTC) is the most common endocrine malignancy and accounts for 1-2% of all cancer cases. Second malignancies in women diagnosed with thyroid cancer are of concern given the young average age at diagnosis. The concurrent occurrence of thyroid cancer and malignant brain tumor such as glioblastoma (GBM) was rarely seen and reported. However, the simultaneous association of these 2 conditions, namely PTC and GBM, in a neurofibromatosis type 1 (NF1) patient, has never been reported before in the literature. Case presentation: The authors report the first case of an extremely rare association combining papillary thyroid carcinoma, glioblastoma, and a neurofibromatosis 1 in a 34-year-old female patient with primary generalized tonic-clonic seizures. Clinical discussion: NF1 can be associated with PTC and GBM independently. In this current case, NF1 was accompanied by both PTC and GBM. With the exception of the present case, to our knowledge, there has been no previous case report in the literature in which these 3 entities were associated. The reason for the rarity of this combination of these neoplasms in patients with NF1 remains not clear, but it may be explained by the low incidence of combined occurrence of PTC and GBM. Conclusion: This is the first reported extremely rare coexistence of GBM and PTC in a female NF1 patient. Further genetic investigations could improve our understanding of this combination and change our therapeutic approaches.

Primary cutaneous Rosai-Dorfman-Destombes disease with features mimicking IgG4-related disease: A challenging case report and literature review.

Rosai-Dorfman-Destombes disease (RDD) is a rare histiocytic disorder affecting lymph nodes as well as extranodal sites. Although cutaneous involvement in RDD is common, primary cutaneous RDD is a distinct and not well-documented entity with unknown aetiology and non-specific clinicopathological features. We report a case of a 57-year-old patient, who presented with an indolent skin nodule in the left sub-nipple area. Surgical excision was performed. Histological examination concluded to the diagnosis of cutaneous RDD with histological features mimicking IgG4-related disease. The diagnosis of systemic RDD with cutaneous involvement was ruled out after exclusion of extracutaneous involvement. No recurrence or systemic progression was observed during follow-up. The diagnosis of primary cutaneous RDD is very uncommon and hence is challenging for pathologist and dermatologist especially with features of IgG4-related disease. Careful systemic and microscopic examinations help in establishing the appropriate diagnosis.

Subacute toxicity studies of meals prepared from genetically modified potato overexpressing the StDREB1 or the VvWRKY2 transcription factor in rats.

BACKGROUND: Potato tubers from genetically modified plants overexpressing the StDREB1 or the VvWRKY2 transcription factors that exhibited improved tolerance to salt and resistance to Fusarium solani infection were characterized and evaluated for safety in a 30 day rat feeding study. Male Wistar rats were split into four groups and provided with a diet composed of 33% (w/w) of either one of the two genetically modified potatoes (GMPs), 33% of the commercial Spunta variety (Sp), or a control group fed with the basal rats' diet. The influence of the GMPs on rat behavior and overall health parameters was evaluated and compared with that of commercial potato (i.e. the Sp group) and control diet. RESULTS: Small differences were noticed in the chemical composition of the different tubers, but all the diets were adjusted to an identical caloric level. Results showed no sign of toxic or detrimental effects on the rats' overall health as a result of these diets. The rats fed with the GMPs meal showed hematological and biochemical compositions of the plasma comparable to the control groups. No histopathological damage nor any structural disorganization, severe congestion, or acute inflammation were noticed in the rats' tissues. CONCLUSION: Under these study conditions, the GMP diets did not induce any apparent or significant adverse effects on rats after 30 days of dietary administration in comparison with rats fed diets with the corresponding non-transgenic diet and the standard diet group. These two GMPs were therefore considered to be as safe as their commercial comparator. © 2022 Society of Chemical Industry.

Liver injury in COVID-19: pathological findings.

Hepatic injuries have been reported in patients with Coronavirus disease 2019 infection, particularly in those with moderate to severe illness. To date, pathological changes caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in liver tissue are unclear. Moreover, the mechanisms involved in liver injury in Coronavirus disease 2019 infection are not yet established. In this paper, we summarize the spectrum of pathologic findings of liver injury in patients infected by SARS-CoV-2 and we discuss the clinicopathological correlation and the mechanisms of liver damage in Coronavirus disease 2019 infection.

A case of adult cerebellar liponeurocytoma with atypical radiological features and long survival with literature review.

Cerebellar liponeurocytoma or lipomatous medulloblastoma is a rare oncological entity. Knowledge regarding the management and outcomes of these rare tumors are still evolving. Very few cases have been described previously in the literature. The authors report a case of a middle-aged woman operated on twice, 8 years apart, with uneventful postoperative follow-ups. Radiological characteristics were revealed atypically on the computed tomography scan and magnetic resonance imaging. Histopathological study supported a cerebellar liponeurocytoma with classic immunohistochemical features. Through this report, the authors aim to describe atypical radiological and histopathological features of this rare entity with good outcome by going through a comprehensive review of the existing literature.

Organized Hematoma of the Maxillary Sinus: Report of Two Cases.

INTRODUCTION: Organized hematoma of the maxillary sinus (OHMS) is a rare benign disease that can be locally aggressive. The diagnosis of this condition is challenging. CASE REPORTS: We report two cases of OHMS presented with recurrent nasal bleeding, nasal obstruction and anosmia. Radiological findings were suggestive of a vascularised lesion in the first case and a malignant tumor of the maxillary sinus in the second case. Both patients underwent an endonasal endoscopic surgery, There was no recurrence at 19 months' and six months' follow-up respectively. CONCLUSIONS: OHMS should be included in the differential diagnosis if a patient presents with history of recurrent epistaxis and nasal obstruction and radiological findings reveal an expansible maxillary mass with or without bone erosion. Correct preoperative diagnosis is important to avoid unnecessary extensive surgery. The prognosis is very good and minimally invasive surgery such as endonasal endoscopic surgery can cure it completely.

Availability, utilization and quality of emergency obstetric care services in Sousse, Tunisia.

INTRODUCTION: emergency obstetric care (EmOC) is a high-impact priority intervention strongly recommended for improving maternal health outcomes. The objectives of this study were to assess the availability, utilization, and quality of emergency obstetric care services in the Governorate of Sousse (Tunisia). METHODS: a cross-sectional study was conducted among public health facilities which performed deliveries in Sousse in 2017. Data were collected by consulting clinical records and registers and interviewing staff using WHO EmOC tools. Emergency obstetric care (EmOC) indicators were calculated. RESULTS: only the University maternity Unit functioned as full comprehensive EmOC facility. No other public facility provided all the 7 Basic EmOC signal functions 3 months prior to the survey. The unperformed signal functions were: administration of parenteral antibiotics, manual removal of placenta and assisted vaginal delivery. The number of EmOC facilities was 0.72 per 500,000 inhabitants. The met need for EmOC was 89.5%. The proportion of caesarean section was 24.2%. The direct obstetric case fatality rate was 0.159% and intrapartum and very early neonatal death rate was 0.65%. CONCLUSION: raising maternity facilities to a minimum level of basic EmOC status would be a major contributing step towards maternal mortality reduction.

Prognostic significance of E-cadherin and Cox 2 expression in Tunisian patients with colorectal mucinous adenocarcinoma.

INTRODUCTION: Mucinous colorectal carcinoma (MC) is a rare subtype of colorectal adenocarcinoma known to be associated with bad prognosis. Lately, research has turned to identify new prognostic markers allowing the use of targeted therapy. The aim of our study is to evaluate the prognostic impact of E-cadherin and Cox-2expression in MC. MATERIALS AND METHOD: A total of 40 formalin-fixed, paraffin-embedded MC specimens were collected within a period of 13 years and were studied for the expression of the two proteins. We used SPSS 22 software to study associations with clinicopathological parameters and overall survival (OS). RESULTS: A reduced or absent E-cadherin expression was noted in 52.5% of cases. It was associated with distant metastases (p = 0.049) and venous invasion (p = 0.049). Cox-2 was overexpressed in 17.5% of cases. It was associated with negative lymph node status (p = 0.020) and with early stage tumor (p = 0.020). A significant association between the two proteins was also noted (p = 0.04). No significant association with OS was found; However, there was an improvement in the survival of patients overexpressing Cox-2 (p = 0.16). CONCLUSION: Our findings link the loss of E-cadherin expression with spread and aggressiveness in MC and Cox-2 overexpression with better prognosis and survival. Because MC has a distinct genetic pathway we encourage the analysis of MSI and Cox-2 expression in all MC. Cox-2 inhibitors may not be effective chemopreventative agents in the setting of defective DNA mismatch repair. More molecular studies are needed to better understand the role of these markers and their prognostic significance in MC.

A novel blue crab chitosan/protein composite hydrogel enriched with carotenoids endowed with distinguished wound healing capability: In vitro characterization and in vivo assessment.

This work aimed to the development of chitosan and protein isolate composite hydrogels, for carotenoids-controlled delivery and wound healing. By increasing the concentration of the protein isolate, chitosan hydrogels were more elastic at a protein isolate concentration not exceeding 15% (w/w). Chitosan-protein isolate composite hydrogels revealed low cytotoxicity towards MG-63 osteosarcoma cells. Thanks to its appropriate structural, swelling and mechanical resistance properties, chitosan hydrogel (3%; w/v), reinforced with 15% (w/w) of protein isolate, was selected for the carotenoids in vitro release study. Release profiles, show delivery patterns, where carotenoids were more barely released at a pH 7.4 medium (p < .05), compared to more acidic microenvironments (pH 4.0 and pH 2.0). Thus, developed hydrogels could be applied as pH-sensitive intelligent carriers, for drugs-controlled release, with interesting antioxidant abilities. The in vivo healing potential of hydrogels in rats' models was further studied. Topical application of hydrogel-based patches allowed the acceleration of wound healing and the complete healing, for composite hydrogel enriched with carotenoids.