Publications by authors named "Nada Lahmidani"

9 Publications

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[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)].

Pan Afr Med J 2021 19;38:382. Epub 2021 Apr 19.

Service d'Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Faculté de Médecine et de Pharmacie de Fès, Université Sidi Mohamed Ben Abdellah, Fès, Maroc.

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.
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http://dx.doi.org/10.11604/pamj.2021.38.382.27235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325451PMC
August 2021

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.

Dis Markers 2021 28;2021:9980410. Epub 2021 Jul 28.

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.

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). . 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.
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http://dx.doi.org/10.1155/2021/9980410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342151PMC
January 2022

Microsatellite Instability Analysis in Gastric Carcinomas of Moroccan Patients.

Genet Test Mol Biomarkers 2021 Feb;25(2):116-123

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.

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. 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. 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 ( = 0.004), tumor location ( < 0.001), and intestinal-type of Lauren classification ( < 0.001). Among the 22 MSI target genes analyzed, the most frequently altered genes were (84.6%), (30.8%), (23.1%), (23.1%), and (23.1%). Multivariate analysis revealed the MSS phenotype (Hazard ratio, 0.23; 95% confidence interval, 0.7-7.4;  = 0.014) as an independent indicator of poor prognosis in our population. 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.
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http://dx.doi.org/10.1089/gtmb.2020.0146DOI Listing
February 2021

Study of predictive factors of complete response after chemoembolization for unresectable hepatocellular carcinoma in 162 patients.

Clin Exp Hepatol 2020 Dec 30;6(4):313-320. Epub 2020 Dec 30.

Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, Morocco.

Aim Of The Study: To study clinical, laboratory and imaging features correlated with complete response (CR) to transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC) through 162 patients collected in Hassan II University Hospital of Fez.

Material And Methods: From January 2015 to December 2019, 162 patients diagnosed with 225 HCC were treated by TACE. Among them, 14 showed CR during the follow-up. Imaging response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). A multivariate analysis was performed including demographic parameters, etiology, α-fetoprotein (AFP) rates, hepatic function scores, imaging and TACE features. In cases with complete response and remission, follow-up duration was considered from the first to the last imaging control showing no viable tumor and eventually nodule retraction.

Results: Among the 162 patients with 225 nodules, 14 (9%) of them showed remission and 148 (91%) did not. There was no significant difference between the two groups in age, performance status (PS), AFP, nodularity, size nodule or number of TACE cures. Sex, etiology, Child-Pugh and MELD scores, location, BCLC stage and blush extinction were all found to have a significant impact on therapeutic response.

Conclusions: This study demonstrates that CR of HCC treated by TACE is strongly correlated with male sex, etiology (viral hepatitis C), location (segments VI and VII) and complete blush extinction on digital subtraction angiography (DSA). No significant correlation was found, particularly that of tumor size and segment IV (as a pejorative location).
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http://dx.doi.org/10.5114/ceh.2020.102169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816630PMC
December 2020

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

Cancer Control 2020 Jan-Dec;27(1):1073274820976596

Department of Pathology, Hassan II University Hospital, Fès, Morocco.

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 59.76, = 0.030). Patients with SRC tend to have more diffuse tumors in the stomach ( = 0.005), with flat macroscopic appearance ( = 0.001). Patients with SRC present more often with pT3 tumors ( < 0.001), lymph node metastasis ( = 0.024) and perineural invasion ( = 0.003). There were no significant differences between SRC and nSRC in gender, vascular invasion or distant metastasis ( > 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 ( = 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.
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http://dx.doi.org/10.1177/1073274820976596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480344PMC
August 2021

[IgG4-related disease: about 3 cases].

Pan Afr Med J 2020 28;36:364. Epub 2020 Aug 28.

Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Ibn Zohr, Agadir, Maroc.

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.
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http://dx.doi.org/10.11604/pamj.2020.36.364.24835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666702PMC
January 2021

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

Dis Markers 2020 11;2020:8459303. Epub 2020 Jan 11.

Laboratory of Biomedical and Translational Research, University of Medicine and Pharmacy of Fez, Morocco.

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 ( = 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 ( = 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 ( = 0.002). Furthermore, the high expression of Ki67 was moderately correlated with an older age ( = 0.016, = 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.
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http://dx.doi.org/10.1155/2020/8459303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977322PMC
September 2020

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

Dis Markers 2019 7;2019:3210710. Epub 2019 Dec 7.

Department of Pathological Anatomy, Hassan II University Hospital, Fez, Morocco.

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. , , and 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 ( = 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 ( = 0.05) after multivariate analysis.
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http://dx.doi.org/10.1155/2019/3210710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925747PMC
May 2020

Noninvasive predictors of presence and grade of esophageal varices in viral cirrhotic patients.

Pan Afr Med J 2015 17;20:145. Epub 2015 Feb 17.

Department of Gastroenterology and Hepatology, University Hospital Hassan II, Faculty of Medicine Fez, Morocco.

Predicting the presence and the grade of varices by non-invasive methods is likely to predict the need for prophylactic beta blockers or endoscopic variceal ligation. The factors related to the presence of varices are not well-defined. Therefore, the present study has been undertaken to determine the appropriateness of the various factors in predicting the existence and also the grade of esophageal varices. Patients with diagnosis of liver cirrhosis due to hepatitis C or B were included in a retrospective study between January 2001 and January 2010. All the patients underwent detailed clinical evaluation, appropriate investigations, imaging studies (ultrasound with Doppler) and endoscopy at our center. Five variables considered relevant to the presence and grade of varices were tested using univariate and multivariate analysis (logistic regression). Three hundred and seventy two patients with viral liver cirrhosis were included, with 192 (51.6%) males. Platelet count and abundance of ascites were significantly associated with the presence of esophageal varices. However, abundance of ascites, prothrombin time, diameter of the spleen and portal vein were significantly associated with a large varice. In multivariate analysis, platelet count inferior to 100000 was associated with presence of varices (p = 0.04) and only abundance of ascites was associated with large varice. Low Platelet count (< or equal 100000) is associated with the presence of varices in viral cirrhotic patients and abundance of ascites is correlated with the presence of large varices.
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http://dx.doi.org/10.11604/pamj.2015.20.145.4320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919668PMC
December 2016
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