Prognostic Impact of Tumor Budding on Moroccan Gastric Cancer Patients.

Background: Tumor budding (TB) has been defined as an independent prognostic factor in many carcinomas like colon adenocarcinoma, but its prognostic impact on gastric cancer patients remains not well established. In the present study, we aimed to highlight the correlation of tumor budding with clinicopathological features and predict its survival outcomes in gastric cancer patients for the first time in the Moroccan population. Methods: This study was conducted on 83 patients who underwent surgery for gastric adenocarcinoma from 2014 to 2020. The patient's clinico-pathological characteristics were obtained from the pathological and clinical records of each patient. Tumor budding was assessed on HES slides, according to the 2016 International Tumor Budding Consensus Conference criteria. The association of tumor budding grades with categorical and continuous variables were respectively assessed by the χ2-test and the unpaired t-test. Survival analysis was performed by the Kaplan-Meier method, the log-rank test. Results: Patients consisted of 65.1% of men and 34.9% of women with a median age of 61.2 years. Histologically, the majority of the tumors were adenocarcinoma (65.1%). Among all cases, 18.1% were classified as Bud1 (15/83), (27/83) 32.5% as Bud 2, and 49.4% (41/83) as Bud 3 grades. High-grade tumor budding (BUD 3) was found to be significantly associated with special clinicopathological features including older age (P = .02), unradical resection (R1/R2) (P = .03), and the presence of vascular invasion (P = .05), and perineural invasion (P = .04). Furthermore, tumors with high-grade tumor budding were significantly associated with a low rate of resected lymph nodes (P = .04) and advanced TNM stage (P = .02). Among all stages, high-grade tumor budding was correlated with shorter overall survival in univariate and multivariate analysis (P = .04). Patients with high-tumor budding had worse relapse-free survival compared with patients with low-tumor budding grade (P = .01). Conclusion: According to our study, the high-tumor budding grade was correlated with unfavorable clinicopathological features and poorer survival. The present study findings suggest that tumor budding should be considered in the treatment and prognosis of gastric cancer patients.

Prognostic Impact of Tumor Budding on Moroccan Colon Cancer Patients.

BACKGROUND: Tumor budding is now emerging as one of the robust and promising histological factors that play an important role in colon cancer. In this study, we aimed to investigate the association between tumor budding and tumor clinicopathological factors, tumor molecular signature, and patient survival for the first time in a Moroccan population. METHODS: We collected data of 100 patients operated from colon adenocarcinoma. Tumor budding was assessed on HES slides, according to the International Tumor Budding Consensus Conference 2016 recommendations. The expression of MMR proteins was performed by immunohistochemistry. KRAS and NRAS mutations testing was performed by Sanger sequencing and pyrosequencing. RESULTS: High tumor budding grade (BUD 3) was found to be significantly associated with adverse clinicopathological features including older age (P=0.03), presence of perineural invasion (P=0.02), presence of vascular invasion (P=0.05), distant metastases (P < 0.001), advanced TNM stage (P=0.001), the occurrence of relapse (P=0.04), and the high number of deceased cases (P=0.02). Interestingly, we found that tumors with high-grade tumor budding were more likely to be microsatellite stable (MSS) (P=0.005) and harbor more KRAS mutations (P=0.02). Tumors with high-grade tumor budding were strongly associated with KRAS G12D mutation (P=0.007). In all stages, high tumor budding was correlated with poorer overall survival (P=0.04) and decreased relapse-free survival with a difference close to significance ((P=0.09). We concluded that high tumor budding was strongly associated with unfavorable clinicopathological features and special molecular biomarkers and effectively affects the overall survival of CC patients. CONCLUSIONS: Based on these findings and the ITBCC group recommendations, tumor budding should be taken into account along with other clinicopathologic factors in the risk assessment of colorectal cancer.

Reproduction of the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) Gastric Cancer Molecular Classifications and Their Association with Clinicopathological Characteristics and Overall Survival in Moroccan Patients.

INTRODUCTION: The Cancer Genome Atlas (TCGA) project and Asian Cancer Research Group (ACRG) recently categorized gastric cancer into molecular subtypes. Nevertheless, these classification systems require high cost and sophisticated molecular technologies, preventing their widespread use in the clinic. This study is aimed to generating molecular subtypes of gastric cancer using techniques available in routine diagnostic practice in a series of Moroccan gastric cancer patients. In addition, we assessed the associations between molecular subtypes, clinicopathological features, and prognosis. METHODS: Ninety-seven gastric cancer cases were classified according to TCGA, ACRG, and integrated classifications using a panel of four molecular markers (EBV, MSI, E-cadherin, and p53). HER2 status and PD-L1 expression were also evaluated. These markers were analyzed using immunohistochemistry (E-cadherin, p53, HER2, and PD-L1), in situ hybridization (EBV and HER2 equivocal cases), and multiplex PCR (MSI). RESULTS: Our results showed that the subtypes presented distinct clinicopathological features and prognosis. EBV-positive gastric cancers were found exclusively in male patients. The GS (TCGA classification), MSS/EMT (ACRG classification), and E-cadherin aberrant subtype (integrated classification) presented the Lauren diffuse histology enrichment and tended to be diagnosed at a younger age. The MSI subtype was associated with a better overall survival across all classifications (TCGA, ACRG, and integrated classification). The worst prognosis was observed in the EBV subtype (TCGA and integrated classification) and MSS/EMT subtype (ACRG classification). Discussion/Conclusion. We reported a reproducible and affordable gastric cancer subtyping algorithms that can reproduce the recently recognized TCGA, ACRG, and integrated gastric cancer classifications, using techniques available in routine diagnosis. These simplified classifications can be employed not only for molecular classification but also in predicting the prognosis of gastric cancer patients.

[Chronic inflammatory bowel diseases: what happens when SARS-CoV-2 occurs? Preliminary results from a study conducted at the Hassan II University Teaching Hospital in Fes, Morocco (a case report)]. / Les maladies inflammatoires chroniques de l'intestin: que se passe-t-il quand le SARS-CoV-2 arrive? Résultats préliminaires du Centre Hospitalier Universitaire Hassan II de Fès, Maroc (à propos d'un cas).

SARS-CoV-2 infection is a major concern and a new threat to immunocompromised patients. Patients with chronic inflammatory bowel diseases (IBDs) are at increased risk of infections, in particular when they have active disease and are on immunosuppressive treatment. The purpose of this study was to assess the clinical, biological and radiological features of three patients with COVID-19 associated with chronic IBD as well as their management and outcomes. The study was conducted at the Hassan II University Teaching Hospital in Fes, Morocco over a 3-month period. We assessed all patients with disease onset. All patients had mild symptoms or were asymptomatic. No changes or delays in treatment regimens occurred and none of patients developed severe COVID-19. Reverse transcription polymerase chain reaction (RT-PCR) test results were positive in all patients. Radiological examinations were conducted. Chest scanner showed ground-glass opacities in one case. Treatment was based on hydroxychloroquine with azithromycin. Outcome was good in all cases. This preliminary report suggests that patients with chronic IBD aren't at higher risk of developing COVID-19 compared to the general population.

Microsatellite Instability Analysis in Gastric Carcinomas of Moroccan Patients.

Aim: To investigate correlations between microsatellite instability (MSI) and the phenotype, clinicopathological features, and overall survival (OS) in Moroccan gastric cancer (GC) patients. We evaluated the mutation frequency of 22 MSI-target genes in MSI-positive tumors. Materials and Methods: MSI evaluation were performed for 97 gastric tumors by multiplex polymerase chain reaction (PCR) using a panel of five quasimonomorphic mononucleotide repeat markers (NR27, NR21, NR24, BAT25, and BAT26). The mutation profiles of 22 MSI-target genes were assessed by multiplex PCR and genotyping. Kaplan-Meier curves, the log-rank test, and the Cox proportional hazard regression model were used to conduct survival analyses. Results: Microsatellite stable (MSS) status was observed in 77/97 (79.4%) gastric cancer samples, MSI-Low in 7 (7.2%) samples, and MSI-High (MSI-H) in 13 (13.4%) cases. The MSI-H phenotype was significantly associated with older age (p = 0.004), tumor location (p < 0.001), and intestinal-type of Lauren classification (p < 0.001). Among the 22 MSI target genes analyzed, the most frequently altered genes were HSP110 (84.6%), EGFR (30.8%), BRCA2 (23.1%), MRE11 (23.1%), and MSH3 (23.1%). Multivariate analysis revealed the MSS phenotype (Hazard ratio, 0.23; 95% confidence interval, 0.7-7.4; p = 0.014) as an independent indicator of poor prognosis in our population. Conclusions: This study is the first analysis of MSI in Moroccan GC patients. MSI-H GCs have distinct clinicopathological features and an improved OS. We have identified candidate target genes altered in MSI-positive tumors with potential clinical implications. These findings can guide immunotherapy designed for Moroccan GC patients.

The Prognostic Value Of The ART Score Before The Second Transarterial Chemoembolization.

The transarterial chemoembolization (TACE) is a firstline therapeutic option for advanced hepatocellular carcinoma (HCC). Their indications are clearly defined by learned societies but the challenge is to determine the optimal number of TACE sessions that will benefit patients before switching to other therapies. For this reason, the Assessment for Retreatment with Transarterial chemoembolization (ART) score has been developed. The objective of our work is to show the prognostic value of the ART score before the second TACE. METHODS: This is a retrospective and prospective study of patients with hepatocellular carcinoma on cirrhosis liver who received a TACE between January 2012 to July 2019. The diagnosis of HCC was made according to the non-invasive criteria of EASL with the use of histology for doubtful cases. The ART score was calculated after the first chemoembolization. Patients were divided into 2groups: group A with an ART score between 0 and 1.5 and group B with a score =2.5. RESULTS: During the study period, 58 patients with HCC on cirrhosis liver received a TACE: 55.17% had an ART score between 0 - 1.5 before the second session and 44.8% had an ART score =2,5. Both groups were comparable regarding age, circumstances of discovery and Child's score. The size of the HCC as well as the value of the AFP was further increased in the group B. We observed a significant difference in the radiological response, the Child score and aspartate transaminase rate between the two groups after the first TACE. The overall survival rate at 3 years was 81% in group A versus 19% in group B. CONCLUSION: The ART score has an independent prognostic value and should be taken into account in the therapeutic strategy before the second TACE.

Gastric Signet Ring Cell Carcinoma: A Comparative Analysis of Clinicopathologic Features.

Signet ring cell carcinoma (SRC) is a distinct histological subtype of gastric carcinoma. Our aim is to investigate differential characteristics between gastric SRC and other non SRC carcinomas (nSRC). It was a retrospective study including 183 patients diagnosed with gastric carcinoma over a period of 5 years at our pathology department. We performed statistical comparison of clinicopathological features between patients with SRC and those with nSRC. 127 patients (69.4%) had nSRC, 56 had SRC (30.6%), the mean age was 56.67 ± 14.03 years. Patients with SRC were younger than those with nSRC (mean age of 49.66 versus 59.76, P = 0.030). Patients with SRC tend to have more diffuse tumors in the stomach (P = 0.005), with flat macroscopic appearance (P = 0.001). Patients with SRC present more often with pT3 tumors (P < 0.001), lymph node metastasis (P = 0.024) and perineural invasion (P = 0.003). There were no significant differences between SRC and nSRC in gender, vascular invasion or distant metastasis (P > 0.05). The median survival time was 42.82 ± 1.70 months. Patients with nSRC live longer than those with SRC, but the difference was not significant (P = 0.28). SRC is a histological subtype of gastric carcinoma with distinctive clinicopathologic features. The clinical management of patients should take into account these particular features.

[IgG4-related disease: about 3 cases]. / La maladie à IgG4: à propos de 3 cas.

IgG4-Related disease (IgG4-RD), formerly known as IgG4-related autoimmune polyexocrinopathy, is a new condition including Plasminogen Activator Inhibitor-1 (PAI-1). It can affect different organs (central nervous system, salivary glands, thyroid, lungs, pancreas, bile ducts, liver, digestive tract, kidneys, prostate, etc.) with symptoms depending on the organ that is affected. It is more common in men older than 50 years of age. Its incidence and prevalence are poorly known because it is an uncommon disease. It is most common in Asia, accounting for only 20-30% of PAI in the Western world. Diagnosis is based on histological examination which shows dense lymphoplasmocytic infiltration in the organ affected associated with IgG4-positive plasma cells (immunohistochemistry), organ fibrosis and obliterating venulitis, all this in the context of increased serum IgG4 levels in more than 80% of cases. Patients are sensitive to corticosteroid therapy, with a high risk of relapse after discontinuation of corticosteroid therapy. This leads to the use of immunomodulators, mainly: thiopurines (azathioprine or 6-mercaptopurine), methotrexate and more recently rituximab, which can also be used as induction therapy. Given recent advances, accurate histological and clinical criteria are currently known to limit inappropriate management such as surgery. However, knowledge gaps remain concerning: pathophysiology, identification of specific biomarkers other than IgG4, natural history of the disease and long-term cancer risk assessment, performances of diagnostic tools such as endoscopic ultrasound-guided pancreatic biopsy. As well, consensual international management should be defined in the early stages of the disease and when patients develop recurrences. The purpose of this study was to report 3 cases of IgG4-Related disease on the basis of clinical and radiological criteria as well as therapeutic response.

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.

Implication of Microsatellite Instability Pathway in Outcome of Colon Cancer in Moroccan Population.

BACKGROUND: Tumors with microsatellite instability (MSI tumors) have distinct clinicopathological features. However, the relation between these tumor subtypes and survival in colon cancer remains controversial. The aim of this study was to evaluate the overall survival (OS) in patients with MSI phenotype, in FES population. METHODS: The expression of MMR proteins was evaluated by immunohistochemistry for 330 patients. BRAF, KRAS, and NRAS mutations were examined by Sanger sequencing and pyrosequencing methods. The association of MSI status with a patient's survival was assessed by the Kaplan-Meier method and log-rank test. RESULTS: The mean age was 54.6 years (range of 19-90 years). The MSI status was found in 11.2% of our population. MSI tumors were significantly associated with male gender, younger patients, stage I-II, right localization, and a lower rate of lymph node and distant metastasis. The OS tends to be longer in MSI tumors than MSS tumors (109.71 versus 74.08), with a difference close to significance (P = 0.05). CONCLUSION: Our study demonstrates that MSI tumors have a particular clinicopathological features. The results of survival analysis indicate that the MSI status was not predictive of improved overall survival in our context with a lower statistical significance (P = 0.05) after multivariate analysis.