In-depth exploration of differences of sex development: 5-year experience in a tertiary center.

BACKGROUND: Differences/disorders of sex development (DSD) encompass a wide range of conditions. Their clinical spectrum and etiological diagnosis have not been reported in Moroccan patients. AIMS: The study aims to highlight the clinical spectrum, etiological diagnosis, and management of patients with DSD. PATIENTS AND METHODS: This is a retrospective study of all patients diagnosed with DSD under the age of 18 years, who were referred to the Pediatric Endocrinology Department and the Medical Genetics Laboratory at HASSAN II University Hospital of Fez between June 2018 and June 2023. RESULTS: Out of 57 patients, 54.4% (n=31) were diagnosed with 46,XX DSD, the most common type, while 45.6% (n=26) had 46,XY DSD. Patients with 46,XX DSD presented earlier than those with 46,XY DSD, at a median age of 0.08 years and 0.96 years, respectively. The most commonly reported complaint was atypical genitalia. At the first presentation, the sex of rearing was already assigned to 26 males and 27 females. All patients with 46,XX DSD were diagnosed with congenital adrenal hyperplasia (CAH) at a median age of diagnosis of 0.92 years. Of these, 11 patients were raised as males. Disorders of androgen action or synthesis were more common in XY patients (69.2%). The consanguinity rate was 46.5%, and there were 19 cases with a positive family history, with 10 siblings having died. CONCLUSION: DSDs are not rare in Morocco. Overall, CAH remains the most frequent DSD etiology. Molecular genetic analyses are needed to determine accurate etiological distribution of DSDs, especially in XY patients.

The prevalence and risk factors for anxiety and depression symptoms among migrants in Morocco.

Humanitarian migration can result in mental health issues among migrants. The objective of our study is to determine the prevalence of anxiety and depression symptoms among migrants and their risk factors. A total of 445 humanitarian migrants in the Orientale region were interviewed. A structured questionnaire was used in face-to-face interviews to collect socio-demographic, migratory, behavioral, clinical, and paraclinical data. The Hospital Anxiety and Depression Scale was used to assess anxiety and depression symptoms. Risk factors for anxiety and depression symptoms were identified using multivariable logistic regression. The prevalence of anxiety symptoms was 39.1%, and the prevalence of depression symptoms was 40.0%. Diabetes, refugee status, overcrowding in the home, stress, age between 18 and 20 years, and low monthly income were associated with anxiety symptom. The associated risk factors for depression symptoms were a lack of social support and a low monthly income. Humanitarian migrants have a high prevalence of anxiety and depression symptoms. Public policies should address socio-ecological determinants by providing migrants with social support and adequate living conditions.

Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report.

This study aimed to estimate the incidence of KRAS, NRAS, and BRAF mutations in the Moroccan population, and investigate the associations of KRAS and NRAS gene mutations with clinicopathological characteristics and their prognosis value. To achieve these objectives, we reviewed medical and pathology reports for 210 patients. RAS testing was investigated by Sanger sequencing and Pyrosequencing technology. BRAF (exon 15) status was analyzed by the Sanger method. The expression of MMR proteins was evaluated by Immunohistochemistry. KRAS and NRAS mutations were found in 36.7% and 2.9% of 210 patients, respectively. KRAS exon 2 mutations were identified in 76.5% of the cases. RAS-mutated colon cancers were significantly associated with female gender, presence of vascular invasion, classical adenocarcinoma, moderately differentiated tumors, advanced TNM stage III-IV, left colon site, higher incidence of distant metastases at the time of diagnostic, microsatellite stable phenotype, lower number of total lymph nodes, and higher means of positive lymph nodes and lymph node ratio. KRAS exon 2-mutated colon cancers, compared with KRAS wild-type colon cancers were associated with the same clinicopathological features of RAS-mutated colon cancers. NRAS-mutated patients were associated with lower total lymph node rate and the presence of positive lymph node. Rare RAS-mutated tumors, compared with wild-type tumors were more frequently moderately differentiated and associated with lower lymph node rate. We found that KRAS codon 13-mutated, tumors compared to codon 12-mutated tumors were significantly correlated with a higher death cases number, a lower rate of positive lymph, lower follow-up time, and poor overall survival. Our findings show that KRAS and NRAS mutations have distinct clinicopathological features. KRAS codon 13-mutated status was the worst predictor of prognosis at all stages in our population.

The Effect of Lymph Nodes' Histologic Response on Survival Outcomes in Moroccan Patients with Rectal Cancer.

Prognosis for patients with locally advanced rectal cancer remains controversial. The purpose of this study was to elucidate possible association between therapeutic effect on lymph nodes (LNs) and patient prognosis. Overall, 149 patients with rectal cancer received preoperative radiotherapy in concomitance with chemotherapy or exclusive radiotherapy before rectal excision. Microscopic examination of formalin-fixed lymph nodes was assessed for therapeutic effect. The establishment of groups combined reaction tissue types of fibrosis, colloid, and necrosis after neoadjuvant treatment was assigned. The average age was 56.38 years, ranged between 22 and 88 years, 53% were female, and 47% were men, with a sex ratio of 1 : 12. In the present study, we noticed that after a median follow-up time of 40.67 months (0-83; SD: 21.1), overall survival was statistically significant depending on age groups. Kaplan-Meier analysis showed significant differences in the rate of patients with an age under 65 years (70.64%) versus those with an age over 85 years (36.5%) (p < 0.001). Also, the OS was statistically significant depending on therapeutic effect groups composed of 0TE (No Therapeutic effect), C+ (presence of only colloidal effect), F+ (presence of only fibrosis tissue), and ME+ (mixture of 2 or 3 types of therapeutic effect) group. Indeed, we observed a significantly higher OS rate in the ME + group (86%) compared with the OS rate of LNs group with no therapeutic effect (57%) (p=0.028). Additionally, there was a significant association between the presence of fibrosis on LNs and an extended delay of more than 8 weeks to neoadjuvant treatment completion and surgery. Our study indicates that the best patient prognosis could be predicted based on tumor presenting a best pathologic effect on lymph nodes, and that delaying surgery for more than 8 weeks to neoadjuvant treatment completion improves therapeutic response on LNs.

Analysis of Molecular Pretreated Tumor Profiles as Predictive Biomarkers of Therapeutic Response and Survival Outcomes after Neoadjuvant Therapy for Rectal Cancer in Moroccan Population.

Pathologic features depending on tumor response to preoperative chemoradiotherapy are important to determine the outcomes in patients with rectal cancer. Evaluating the potential predictive roles of biomarker expression and their prognostic impact is a promising challenge. We reported here the immunohistochemical staining of a panel marker of mismatch repair protein (MMR), Ki67, HER-2, and p53. Additionally, identification of somatic mutations of KRAS, NRAS, and BRAF genes were performed by direct sequencing and pyrosequencing in pretreated biopsy tissues from 57 patients diagnosed for rectal cancer. Clinical features and pathological criteria for postneoadjuvant treatment surgical resection specimen's data were collected. Immunohistochemical expression and mutational status were correlated with therapeutic response, overall survival, and disease progression. The mean age of patients was 56 years. Seven (12.3%) out of 57 patients had a complete therapeutic response. Our analysis showed that when using complete therapeutic response (Dworak 4) and incomplete therapeutic response (Dworak 3, 2, and 1) as grouping factor, high p53 expression at the pretreatment biopsy was significantly associated to an incomplete response (p = 0.002). For 20 and 2 out of 57, KRAS and NRAS mutations were detected, respectively. The majority of these mutations affected codon 12. KRAS mutations detected at codon 146 (A146T, A146V) was associated with the appearance of recurrence and distant metastasis (p = 0.019). A high expression of HER-2 corresponding to score 3+ was observed in 3 pretreatment biopsy specimens. This class was significantly associated with a short relapse-free survival (p = 0.002). Furthermore, the high expression of Ki67 was moderately correlated with an older age (p = 0.016, r = 0.319). In addition, this shows that high p53 expression in the pretreatment biopsy was associated with an incomplete response in surgical resection specimens after neoadjuvant treatment, and a HER-2 score 3+ can be a predictive factor of distant metastasis and local recurrence. Larger, prospective, and more studies are needed.

The Assessment of HER2 Gene Status by Fluorescence In Situ Hybridization in Invasive Breast Carcinomas With Equivocal HER2 Immunostaining: Experience From a Single Institution.

BACKGROUND: A subset of breast carcinomas harbors overexpression of the human epidermal growth factor receptor 2 (HER2). Fluorescence in situ hybridization (FISH) should be performed in breast carcinomas with equivocal HER2 immunostaining (immunohistochemistry [IHC] HER2 2+). The aim of our study is to investigate clinicopathologic factors associated with HER2 status in breast invasive carcinomas with IHC HER2 2+ through FISH analysis. METHODS: This is a retrospective study including the FISH analysis of 111 patients with invasive breast carcinomas with equivocal HER2 immunostaining. RESULTS: The mean age was 49.51 ± 10.48 years, and invasive breast carcinoma of no special type was the most histological type in our study (96.4%). Most patients had tumors positive for hormones receptors (88.2% positive for estrogen receptor and 81.4% for progesterone receptor). On FISH, the HER2 amplification rate was 22.5%. There was no significant association of HER2 status with any clinicopathologic factors ( P > .05). CONCLUSIONS: Our study shows that there are no reliable clinicopathologic factors to predict the HER2 status in breast tumors with equivocal HER2 immunostaining, supporting the necessary usage of FISH in such circumstances.