Publications by authors named "Sidi Adil Ibrahimi"

27 Publications

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Prognostic Impact of Tumor Budding on Moroccan Colon Cancer Patients.

Int J Surg Oncol 2022 21;2022:9334570. Epub 2022 Jan 21.

Laboratory of Anatomic and Molecular Pathology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

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 (=0.03), presence of perineural invasion (=0.02), presence of vascular invasion (=0.05), distant metastases ( < 0.001), advanced TNM stage (=0.001), the occurrence of relapse (=0.04), and the high number of deceased cases (=0.02). Interestingly, we found that tumors with high-grade tumor budding were more likely to be microsatellite stable (MSS) (=0.005) and harbor more KRAS mutations (=0.02). Tumors with high-grade tumor budding were strongly associated with KRAS G12D mutation (=0.007). In all stages, high tumor budding was correlated with poorer overall survival (=0.04) and decreased relapse-free survival with a difference close to significance ((=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.
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http://dx.doi.org/10.1155/2022/9334570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799359PMC
February 2022

[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

Acute Hepatitis Induced by Intravesical BCG Therapy: A Rare but Serious Complication.

Case Reports Hepatol 2021 24;2021:4574879. Epub 2021 Jun 24.

Faculty of Medicine and Pharmacy of Fez, Sidi Mohamed Ben Abdellah University Fez-Morocco, Fes, Morocco.

Bacillus Calmette and Guérin (BCG), widely used as a vaccination to prevent tuberculosis, is also used as immunotherapy, by intrabladder instillation, to treat superficial bladder cancers and prevent recurrence. Complications following instillation of BCG are most often localized reactions, such as cystitis or hematuria. They can more rarely be generalized and potentially severe such as hepatitis, pneumopathies, aortitis, and localization to hematopoietic tissue. We have reported the observation of a 47-year-old patient followed up for a bladder tumor operated for transurethral resection of the bladder, then having benefited from an instillation of BCG therapy complicated by occurrence a week later of an acute hepatitis. The diagnostic time was 2 days, and the outcome was favorable with corticosteroid therapy.
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http://dx.doi.org/10.1155/2021/4574879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253630PMC
June 2021

CagE, cagA and cagA 3' region polymorphism of Helicobacter pylori and their association with the intra-gastric diseases in Moroccan population.

Diagn Microbiol Infect Dis 2021 Jul 13;100(3):115372. Epub 2021 Mar 13.

Laboratoire de Pathologie Humaine Biomédecine et Environnement, Equipe micro-organismes génomique et facteurs oncogènes, Faculté de médecine et de Pharmacie de Fès (FMPF), Université Sidi Mohammed Ben Abdellah (USMBA), Fès, Maroc.; Laboratoire de microbiologie et de Biologie Moléculaire, FMPF, USMBA. Electronic address:

Helicobacter pylori infection is the most important etiological factor in gastroduodenal diseases development. Its evolution is influenced by several factors, including bacterial virulence genes such as cagA and cagE. This work aimed to evaluate the predictive value of cagE alone and in combination with cagA and CagA-EPIYA-C motifs number as a marker of the infection evolution. A total of 823 H. pylori DNA extracted from biopsies of consenting patients suffering from gastritis, peptic ulcer, or gastric cancer. The cagE, cagA status and cagA 3' region polymorphism were determined by PCR. The analysis shows that the risk of duodenal ulcer is 1.97-fold higher (CI = 1.18-3.30) in patients infected by strains cagA+/cagE+. And the risk of gastric cancer is 5.19-fold higher (CI = 1.18-22.70) in patients harboring strains cagE+/2EPIYA-C. The results suggest that cagE in combination with cagA-EPIYA-C motifs number can be used as predictive biomarker of H. pylori infection evolution.
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http://dx.doi.org/10.1016/j.diagmicrobio.2021.115372DOI Listing
July 2021

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

PLoS One 2021 30;16(3):e0248522. Epub 2021 Mar 30.

Faculty of Medicine and Pharmacy, Laboratory of Biomedical and Translational Research, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248522PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009361PMC
October 2021

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

[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

Modified Mediterranean diet score adapted to a southern Mediterranean population and its relation to overweight and obesity risk.

Public Health Nutr 2021 09 29;24(13):4064-4070. Epub 2020 Jul 29.

Department of Epidemiology and Public Health, Faculty of Medicine, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Objectives: The current study aimed to develop a modified Mediterranean diet (MMD) score adjusted to the southern Mediterranean countries' cultural specificities and to evaluate associations between adherence to this modified score and overweight/obesity risk in Moroccan adults.

Design: Population-based cross-sectional study.

Setting: Rural and urban areas of the five greatest provinces of Morocco.

Participants: In total, 1516 participants were recruited between September 2009 and February 2017. Dietary assessment was obtained using a validated Moroccan FFQ. We constructed a MMD score focusing on twelve components. The MMD score ranged from 0 (no adherence to the traditional southern Mediterranean diet (MD)) to 12 (maximal adherence) and was categorised as low (scores 0-4), moderate (scores 5-7) and high (scores 8-12).

Results: Among the whole population, 754 (50·5 %) were women and 738 (49·5 %) were men, and the mean age was about 55·60 ± 13·70. In total, 58 % of participants were moderately active. Regarding educational level, 50·7 % were illiterate. The prevalence of overweight and obesity was 43·3 and 8·6 %, respectively. In multivariate analyses, close adherence to MMD (scores 8-12) was associated with reduced overweight/obesity risk (OR 0·61, 95 % CI 0·44, 0·84).

Conclusion: The prevalence of overweight and obesity was very high among Moroccan adults. Adherence to the traditional southern MD may help prevent overweight and obesity.
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http://dx.doi.org/10.1017/S1368980020002062DOI Listing
September 2021

VacA genotypes and cagA-EPIYA-C motifs of Helicobacter pylori and gastric histopathological lesions.

Int J Cancer 2020 12 6;147(11):3206-3214. Epub 2020 Jul 6.

Laboratoire de Pathologie Humaine Biomédecine et Environnement, Faculté de Médecine et de Pharmacie de Fès (FMPF), Université Sidi Mohammed Ben Abdellah (USMBA), Fès, Morocco.

Helicobacter pylori infection induces inflammation of the gastric mucosa, which may progress to precancerous lesions and gastric cancer. The gastric histo-pathological damages may be associated with some virulence genes of the bacterium, notably vacA and cagA genes. To establish correlations between these genes and the lesions, biopsies from 1303 adults consenting patients that were previously analyzed by PCR to characterize vacA-s vacA-m, vacA-i regions and cagA 3' region polymorphism, were used. The highest average age was obtained in patients with intestinal metaplasia (53.65 ± 15.26 years) and gastric cancer (53.60 ± 14.32 years). Thus, these lesions are more frequent in elderly and male subjects. Tobacco smoking was significantly associated with neutrophilic activity (P = .02). No significant association was obtained between patients with chronic inflammation and vacA and cagA H. pylori genotypes. However, a significant association has been obtained between this lesion and cagA+ in aged patients (P = .02), while intestinal metaplasia was significantly associated with vacAi1 and vacAm1 separately (P < .01 and .01). Also, a significant association was obtained between intestinal metaplasia and strains with one EPIYA-C motif in young patients (P = .001). Interestingly, a significant association was obtained between gastric cancer and cagA+, vacAi1, vacAm1 H. pylori genotypes and also with two EPIYA-C motifs independently of age groups (all P < .05). The results of our study show that H. pylori vacAi1 could be more potent than the other H. pylori virulent factors for predicting the precancerous gastric lesions, confirming that this gene may be helpful to identify patients at high risk for gastric cancer.
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http://dx.doi.org/10.1002/ijc.33158DOI Listing
December 2020

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

Int J Surg Oncol 2020 6;2020:8406045. Epub 2020 Jan 6.

Laboratory of Biomedical and Translational Research. University of Medicine and Pharmacy of Fez, University Sidi Mohammed Ben Abdellah of Fez, 30070 Fez, Morocco.

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%) ( < 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%) (=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.
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http://dx.doi.org/10.1155/2020/8406045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183526PMC
December 2020

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

Behavioral, Nutritional, and Genetic Risk Factors of Colorectal Cancers in Morocco: Protocol for a Multicenter Case-Control Study.

JMIR Res Protoc 2020 Jan 13;9(1):e13998. Epub 2020 Jan 13.

Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Background: Colorectal cancer (CRC) has been reported as the third most commonly diagnosed cancer worldwide and is currently considered as a major public health concern. A peak increase in incidence has been noted in economically transitioning countries like Morocco where industrialization started shifting from a traditional lifestyle and diet toward a more westernized diet and lifestyle.

Objective: This paper aims to present the protocol of a large-scale Moroccan case-control study that aims at investigating associations of diet, other lifestyle factors, and genetic traits with CRC risk in Morocco.

Methods: A case-control study was conducted between 2009 and 2017, including 3032 case-control pairs (1516 cases and 1516 controls) matched on sex, age, and center in 5 major public health hospitals in Morocco. Questionnaires on sociodemographic data, lifestyle, family history of CRC, and nonsteroidal anti-inflammatory drugs (NSAIDs) were completed by trained investigators during face-to-face interviews. In addition, participants completed a semiquantitative food-frequency questionnaire, developed to assess food intake in the Moroccan population. Information regarding genetic factors was recorded for cases, and paraffin blocks (with embedded tumor tissues) are available in 3 collaborating hospitals. Conditional logistic regression analysis is planned to assess associations between diet and CRC risk. Binary logistic regression is considered to predict associations between mutations and nutritional risk factors including only CRC case series.

Results: Altogether, 2966 cases-control pairs (1483 cases and 1483 controls) were considered eligible and included in this study. Both cases and controls did not differ significantly with respect to age (P=.36), sex (P=.51), center (P>.99), marital status (P=.30), and NSAID use (P=.08). However, participants in the control group were significantly more likely to have a high income level and live in urban areas and to have a high level of education than cases.

Conclusions: This is the first study investigating potential risk factors of CRC such as lifestyle, diet, and genetic factors, originating from a southern Mediterranean country with low but increasing CRC prevalence. Identified risk factors allow the establishment of evidence-based preventive actions regarding nutrition and other lifestyle habits adapted to the Moroccan context. In brief, this study will promote cancer research and prevention in Morocco.

International Registered Report Identifier (irrid): RR1-10.2196/13998.
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http://dx.doi.org/10.2196/13998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006499PMC
January 2020

Concordance with the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention and colorectal cancer risk in Morocco: A large, population-based case-control study.

Int J Cancer 2019 10 29;145(7):1829-1837. Epub 2019 Mar 29.

Department of Epidemiology and Public Health, Faculty of Medicine and pharmacy of Fez, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

The present study aimed to investigate associations between adherence to the recommendations on cancer prevention from the WCRF/AICR and colorectal cancer (CRC) risk in Morocco. Incident CRC cases (n = 1,516) and controls (n = 1,516) matched on age, sex and center, were recruited between September 2009 and February 2017 at five major hospitals located in Morocco. In-person interviews were conducted to assess habitual diet using a validated Food Frequency Questionnaire, physical activity and anthropometric measurements. Adherence to the WCRF/AIRC Recommendations was ranged from 0 (no adherence) to 6 (maximal adherence) and incorporating six WCRF/AICR components (food groups, physical activity and BMI). Multivariable odd ratios (OR ) and 95% confidence intervals (CI) were calculated using conditional multivariate logistic regression models, with low adherence as referent, adjusting for potential confounding factors. Compared to those with the lowest adherence score, individuals in the highest WCRF/AICR score category had a statistically significant reduced risk for colon cancer (OR  = 0.63, 95% CI 0.53-0.76); rectal cancer (OR  = 0.52, 95% CI 0.43-0.63) and CRC overall (OR  = 0.58, 95% CI 0.51-0.66). For individual score components, when comparing the lowest with the highest adherence category, CRC risk was significantly lower in the highest adherence category for body fatness (OR = 0.73; 95% CI 0.62-0.85), physical activity (OR = 0.70; 95% CI 0.60-0.82), plant foods (OR = 0.50; 95% CI 0.39-0.63) and red/processed meat (OR = 0.81; 95% CI 0.71-0.92). Our analysis indicated that greater adherence to the WCRF/AICR recommendations for cancer prevention may lower CRC risk in Morocco.
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http://dx.doi.org/10.1002/ijc.32263DOI Listing
October 2019

Helicobacter pylori CagA EPIYA-C motifs and gastric diseases in Moroccan patients.

Infect Genet Evol 2018 12 19;66:120-129. Epub 2018 Sep 19.

Laboratoire de Microbiologie et Biologie Moléculaire, Equipe micro-organismes génomique et facteurs oncogènes, Faculté de Médecine et de Pharmacie de Fès (FMPF), Université Sidi Mohammed Ben Abdellah (USMBA), Morocco; Laboratoire de Pathologie Humaine, Biomédecine et Environnement, FMPF, USMBA, Morocco. Electronic address:

Background: The pathogenicity of cagA-positive H. pylori strains is associated with the number and type of repeated sequences named EPIYA located in the C-terminal region of the CagA protein. The aim of this study is to determine the polymorphism of the H. pylori cagA 3' region circulating in Morocco and its association with different gastric pathologies.

Methods: A total of 1353 consenting patients, were recruited in this study. The gastric biopsies performed during endoscopy were used for histological examination and for molecular characterization of H. pylori. The study of the type and number of "EPIYA" motif was identified by PCR directly on H. pylori positive biopsies.

Results: Of all the biopsies, the infection rate was 61.1%. The cagA gene was amplified in 68.9% of the cases and the analysis of the 3' region of cagA showed the exclusive presence of the "Western CagA" type with a predominance of the EPIYA-ABC motif (71.4%). The number of EPIYA-C motif varies from 0 to 2. The multinomial analysis shows that the infection with strains of H. pylori having two EPIYA-C motifs is a factor that increases the risk of developing gastric cancer compared to gastritis cases with strains lacking this motif (OR = 11.64; CI: 3.34-45.15), whereas this risk is 6 fold higher in comparison with duodenal ulcer cases (OR = 6, CI: 1.29-27.76).

Conclusions: The results of this study suggest that the number of EPIYA-C motifs might be useful as a predictive marker of the infection evolution and will help in the identification of patients at high risk of developing gastric cancer.
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http://dx.doi.org/10.1016/j.meegid.2018.09.015DOI Listing
December 2018

VacA and CagA Status as Biomarker of Two Opposite End Outcomes of Helicobacter pylori Infection (Gastric Cancer and Duodenal Ulcer) in a Moroccan Population.

PLoS One 2017 26;12(1):e0170616. Epub 2017 Jan 26.

Laboratoire de Microbiologie et de Biologie Moléculaire, Equipe Micro-organismes, Génomique et Facteurs Oncogènes, Faculté de Médecine et de Pharmacie de Fès (FMPF), Université Sidi Mohammed Ben Abdellah (USMBA), Fez, Morocco.

Helicobacter pylori (H. pylori) infection induces inflammation of the gastric mucosa, which may progress to precancerous lesions leading to gastric cancer. Pathological determinism is associated to some virulence genes of the bacterium, notably the vacA and cagA genes. The present study aimed to determine the H. pylori genotypes distribution and their association with sex, age and gastric diseases in a Moroccan population. Gastric biopsy was taken from 1079 consenting patients. The specimens were processed by PCR to identify H. pylori and to determine the genotypic profile by PCR characterizing vacA s, vacA m and vacA i regions directly from biopsies H. pylori positives. VacA genotyping revealed the predominance of vacA m2 (53.2%), vacA s2 (52.9%) and vacA i2 (52%). The most virulent vacA alleles (s1, i1 and m1) are more predominant in men (47.3%, 41.9% and 46.1% respectively) than in women (38.3%, 33.3% and 37% respectively). However, the association between vacA genotypes and age did not reach a statistical significant value. Logistic regression analysis results show that vacA i1m1 and vacA i1m2 genotypes were strongly associated with the risk of GC, the Odds Ratio (95% confidence interval) was 29.73 [5.08-173.73] and 9.17 [2.06-40.82] respectively, while vacAs1/cagA+ seems to be a risk factor for DU since it is inversely associated with GC (OR was 0.13 [0.02-0.75]. The results of this study suggest that vacA i1 genotype independently to vacAm status may be of a clinical usefulness and will help to identify patients at a high risk of GC development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170616PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5268467PMC
August 2017

Detection of Helicobacter pylori urease antigen in saliva in patients with different gastric H. pylori status.

J Chin Med Assoc 2016 Jul 10;79(7):363-7. Epub 2016 Apr 10.

Laboratoire de Microbiologie et de Biologie Moléculaire, Equipe Micro-organismes Génomique et Facteurs Oncogènes, Faculté de Médecine et de Pharmacie de Fès (FMPF), Université Sidi Mohammed Ben Abdellah (USMBA), Fez, Morocco; Laboratoire de Biotechnologie, Faculté des Sciences Dhar el Mehraz, USMBA, Fez, Morocco; Laboratoire de Pathologie Humaine, Biomédecine et Environnement, FMPF, USMBA, Fez, Morocco. Electronic address:

Background: Finding a simple, accurate, and noninvasive diagnosis method is a substantial challenge for the detection of Helicobacter pylori. The aim of the present study was to compare the presence of H. pylori urease antigen in saliva with the presence of this bacterium in gastric mucosa.

Methods: Saliva samples and gastric biopsies were taken from 153 consenting Moroccan patients. Saliva samples were analyzed using an immunochromatographic test for urease antigen H. pylori detection. Thereafter, the gastric biopsies were analyzed by histology and polymerase chain reaction (PCR) to detect this bacterium.

Results: From a total of 153 recruited Moroccan patients, H. pylori was detected in 28 (18.30%), 87 (57.24%), and 69 (45.10%) cases by saliva test, histology, and PCR, respectively. A significant association was observed between the presence of H. pylori antigen in saliva and age. However, no association was found with sex, H. pylori virulence factors, gastric disease outcome, and density of the bacterium on the gastric mucosa. Considering that only 90 patients presented concordant results on H. pylori diagnosis (positive or negative) by both histology and PCR, the immunochromatographic test showed very low sensitivity (29.79%) and high specificity (90.70%). Of these two tests, the positive and negative predictive values were 77.78% and 54.17%, respectively. The accuracy of the test for salivary detection of urease antigen H. pylori was 58.89%.

Conclusion: This study demonstrated a low detection rate of H. pylori antigens in saliva compared with the presence of this bacterium in gastric mucosa, suggesting that saliva cannot be used as a suitable sample for the diagnosis of H. pylori in our study population.
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http://dx.doi.org/10.1016/j.jcma.2016.01.017DOI Listing
July 2016

Epigenetics could explain some Moroccan population colorectal cancers peculiarities: microsatellite instability pathway exploration.

Diagn Pathol 2015 Jun 24;10:77. Epub 2015 Jun 24.

Department of pathology, University hospital Hassan II of Fez, Fez, Morocco.

Background: Colorectal Cancers (CRC) are one of the most common malignancies in the world. Their incidence in Morocco, between 2005 and 2007, was 5.6 for 100000 inhabitants, which is very low compared to what found in developed countries. In addition, CRCs show a high frequency of rectal localizations, and occurs in a younger population in Morocco compared to what found in developed countries. The purpose of this study is to confirm these CRC peculiarities in Morocco and try to explain them by exploring the microsatellite instability molecular pathway.

Methods: This is a prospective observational study conducted since January 2010, including 385 patients admitted in Hassan II University Hospital of Fez. We collected clinical, radiological and pathological data. We investigated the expression of mismatch repair (MMR) proteins in 214 patients and BRAF gene mutations in 159 patients.

Results: Mean age was 55.08 +/- 15.16 years. 36.5% of patients were less than 50 years old and 49.3% of tumors were localized in the rectum. Loss of MMR protein expression was observed in 11.2% of cases. It was independently associated with individual or family history of cancer belonging to Hereditary Non-Polyposis Colorectal Cancer (HNPCC) spectrum (p = 0.01) and proximal localization (p = 0.02). No BRAF mutation was detected in all cases.

Conclusions: These results confirm the high occurrence of CRCs to young patients and the high frequency of rectal localizations in Moroccan population. They mostly show an absence of BRAF mutation, supposing a rarity of MLH1 promoter hypermethylation pathway, which may even partially explain the CRC peculiarities in our context.

Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5868184711716884.
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http://dx.doi.org/10.1186/s13000-015-0326-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477595PMC
June 2015

Non invasive assessment of liver fibrosis in chronic hemodialysis patients with viral hepatitis C.

Pan Afr Med J 2015 23;22:273. Epub 2015 Nov 23.

Gastroenterology Department, University Hospital Hassan II, Fez, Morocco.

The liver biopsy has long been the "gold standard" for assessing liver fibrosis in patients with hepatitis C. It's an invasive procedure which is associated with an elevated bleeding, especially in chronic hemodialysis patients. Main goal is to assess liver fibrosis in chronic hemodialysis with HCV by Fibroscan and by biological scores (APRI, Forns and Fib-4), and to measure the correlation between these tests. Cross-sectional study including all chronic hemodialysis patients with hepatitis C virus, in two public hemodialysis centers of Fez. All patients were evaluated for liver fibrosis using noninvasive methods (FibroScan and laboratory tests). Subsequently, the correlation between different tests has been measured. 95 chronic hemodialysis were studied, twenty nine patients (30.5%) with chronic hepatitis C. The average age was 52.38 ± 16.8 years. Nine liver fibrosis cases have been concluded by forns score. Fibroscan has objectified significant fibrosis in 6 cases. On the other side APRI has objectified sgnifivant fibrosis only in 3 cases. The Fib-4 showed severe fibrosis in five cases. The results have been most consistent between APRI and Fib-4, followed by Fibroscan and Forns, then APRI and FibroScan.
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http://dx.doi.org/10.11604/pamj.2015.22.273.2311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765332PMC
December 2016

Helicobacter pylori genotypes associated with gastric histo-pathological damages in a Moroccan population.

PLoS One 2013 9;8(12):e82646. Epub 2013 Dec 9.

Laboratoire de Microbiologie et Biologie Moléculaire, Equipe micro-organismes et facteurs oncogènes, Faculté de médecine et de Pharmacie de Fès (FMPF), Université Sidi Mohammed Ben Abdellah (USMBA), Fès, Maroc ; Laboratoire de Biotechnologie, Faculté des sciences Dhar el Mehraz, USMBA, Fès, Maroc ; Laboratoire de Biologie des cancers, FMPF, USMBA, Fès, Maroc.

H. pylori persistent infection induces chronic gastritis and is associated with peptic ulcer disease and gastric carcinoma development. The severity of these diseases is related to human's genetic diversity, H. pylori genetic variability and environmental factors. To identify the prevalence of histo-pathological damages caused by H. pylori infection in Moroccan population, and to determine their association to H. pylori genotypes, a prospective study has been conducted during 3 years on patients attending the gastroenterology department of Hassan II University Hospital (CHU) of Fez, Morocco. A total of 801 Moroccan adults' patients were recruited; H. pylori was diagnosed and genotyped by PCR in biopsy specimens and histological exam was performed. We found a high rate of glandular atrophy. Chronic inflammation, neutrophil activity and glandular atrophy showed statistically significant association with H. pylori infection. However, intestinal metaplasia was inversely associated to this infection and no association was observed with gastric cancer cases. A statistically significant association was found between intestinal metaplasia and vacAs1 and vac Am1 genotypes in patients aged 50 years and more but not in younger. This last genotype is also associated to gastric cancer. In this study, gastric cancer showed no significant association with H. pylori. Further studies are warranted to determine the role of other etiological agents such as Epstein-Barr virus, human papillomavirus and possibly environmental and dietetic factors in the occurrence of this pathology.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082646PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857243PMC
October 2014

Esophageal variceal ligation in the secondary prevention of variceal bleeding: Result of long term follow-up.

Pan Afr Med J 2013 3;15. Epub 2013 May 3.

Department of Hepato Gastroenterology Hassan II University Hospital Fez, Morocco.

Introduction: Long-term outcome of patients after band ligation have been poorly defined. Therefore, we conducted a long-term follow-up study to delineate the outcome of ligation in patients with portal hypertension in the Hassan II university hospital, Fes, Morocco.

Methods: Over 118 months patients treated by endoscopic variceal ligation were received regular follow- up and detailed clinical assessment of at least 24 months.

Results: One hundred twenty five patients were followed up for a mean of 31 months (range 12-107 months). Obliteration of the varices was achieved in 89.6 % (N = 112) of patients, with 3 +/-1.99 (range 1-8) endoscopy sessions over a period of 14 + /-6.8 weeks (range 3-28). The percentage of variceal recurrence during follow-up after ligation was 20.5 % (N = 23). Recurrence were observed in a mean of 22 months +/- 7.3 (range 3-48). Bleeding rate from recurrent varices was 30.4 % (7/23). Rebleeding from esophageal ulcers occurred in 5.6 % (7/125) of patients. Portal hypertensive gastropathy before and after eradication of varices was 17.6% (N = 22) and 44.6% (N = 50) respectively; p< 0.05. Fundal gastric varices was 30.4% (N = 38) and 35.7% (N = 40) before and after eradication of varices respectively; p> 0.05. The overall mortality was 4 % (N = 5).

Conclusion: Band ligation was an effective technical approach for variceal obliteration with low rates of variceal recurrence, rebleeding and development of gastric varices. Furthermore, it was associated with frequent development of portal hypertensive gastropathy.
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http://dx.doi.org/10.11604/pamj.2013.15.3.2098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708329PMC
February 2014

Esophageal variceal ligation for hemostasis of acute variceal bleeding: efficacy and safety.

Pan Afr Med J 2013 10;14:95. Epub 2013 Mar 10.

Department of Hepato Gastroenterology Hassan II University Hospital Fez, Morocco.

Introduction: Endoscopic variceal ligation is widely accepted as the optimum endoscopic treatment for esophageal variceal hemorrhage. In Morocco, there are no data regarding the efficacy of this technique. Our aim was to evaluate the effectiveness and safety of endoscopic variceal ligation in the management of oesophageal variceal bleeding in cirrhosis in a located population in Morocco.

Methods: Via a retrospective study over 118 months (December 2001- October 2011), cirrhotic patients with endoscopically proven esophageal variceal hemorrhage were treated by endoscopic variceal ligation. We studied the rate of haemostasis, rebleeding, complications and mortality.

Results: 360 cirrhotic patients were included and 378 haemostatic variceal ligations were performed. Primary haemostasis was obtained in 96.5 % (N=365) of cases. Thirty three patients (8.7%) bled during follow-up. The rate of minor complications was 15.3 % (N=58). Retrosternal pain, fever, dysphagia and Overtube's migration developed in 8.4 % (N=32); 2.6 % (N=10); 3,7 % (N=14) and 0.5 % (N=2) of the patients respectively. Severity of these complications was mild and transient. The rate of oesophageal ulcers was 5 % (N=19), while the mortality rate by haemorrhage was 5 % (N=18).

Conclusion: Our data showed that band ligation is an effective and safe treatment modality of esophageal variceal bleeding with low rates of rebleeding and complications.
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http://dx.doi.org/10.11604/pamj.2013.14.95.1847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664877PMC
September 2013

Prevalence of Helicobacter pylori and its recurrence after successful eradication in a developing nation (Morocco).

Clin Res Hepatol Gastroenterol 2013 Nov 6;37(5):519-26. Epub 2013 Apr 6.

Department of Hepato-Gastroenterology, Hassan II University Hospital, Fez, Morocco. Electronic address:

Introduction: In developed countries, reinfection after successful eradication of Helicobacter pylori appears unusual. High prevalences of H. pylori in developing countries may result in high reinfection rates. In Morocco, published studies regarding the prevalence of H. pylori are limited, and to our knowledge, there are no data regarding the reinfection rate of H. pylori after successful treatment.

Aim: The aim of this study was to determine the prevalence of H. pylori in our area, and the reinfection rate at 6 months and 1 year of follow-up after successful eradication.

Methods: Consecutive patients with investigated ulcer or non-ulcer dyspepsia were prospectively enrolled in the Hassan II University Hospital of Fez. Patients with H. pylori infection were treated with a 1-week triple therapy or 10 day sequential therapy. Those tested urea breath test negative after 3 months of treatment were followed prospectively with repeated urea breath test at 6 months and 1 year. H. pylori status at endoscopic examination was determined by rapid urease test, histology, and culture.

Results: Four hundred and twenty-nine patients were enrolled in the study, among them 324 patients (75.5%) presented with H. pylori infection. Two hundred and fifty-six (83.3%) patients had successfully eradicated H. pylori following treatment, among them, two patients (0.8%) were reinfected with H. pylori over 12 months. The rate of reinfection was 0.42% in the first 6 months and of 0.45% in the first year of the study.

Conclusion: The results of the present study demonstrate that firstly, prevalence of H. pylori is high (75.5%) in our area, secondly as in developed countries, there is a low (0.8%) but continuous risk of H. pylori infection in adulthood. A different approach for follow-up after H. pylori eradication is probably needed in patients of developing countries, since reinfection prevalence is different between countries.
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http://dx.doi.org/10.1016/j.clinre.2013.02.003DOI Listing
November 2013

Small bowel adenocarcinoma complicating coeliac disease: a report of three cases and the literature review.

Case Rep Oncol Med 2012 1;2012:935183. Epub 2012 Dec 1.

Department of Medical Oncology, Hassan II University Hospital, Fez, Morocco.

Coeliac disease is associated with an increased risk of malignancy, not only of intestinal lymphoma but also of small intestinal adenocarcinoma which is 82 times more common in patients with celiac disease than in the normal population. We report three additional cases of a small bowel adenocarcinoma in the setting of coeliac disease in order to underline the epidemiological features, clinicopathological findings, and therapeutic approaches of this entity based on a review of the literature. The three patients underwent a surgical treatment followed by adjuvant chemotherapy based on capecitabine/oxaliplatin regimen, and they have well recovered.
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http://dx.doi.org/10.1155/2012/935183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517832PMC
December 2012

Acute inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alfa-2a in a patient with chronic hepatitis C virus infection: a case report.

J Med Case Rep 2012 Sep 4;6:278. Epub 2012 Sep 4.

Gastroenterology Unit, Hospital University Hassan II, Fez, Morocco.

Introduction: The combination of polyethylene glycol (PEG)ylated interferon (pegylated interferon) and ribavirin has been shown to be an effective treatment for chronic hepatitis C virus. In general, common side effects related to this combination therapy are mild and are well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to PEG-interferon α2a (pegylated interferon alfa-2a) is extremely rare. In the literature, only one case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon α2a has been published previously.

Case Presentation: To the best of our knowledge we present only the second case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon α2a, occurring in a 63-year-old Caucasian man. He developed tingling, numbness, and weakness of his upper and lower extremities with acute neurological deficits after five weeks of a combination therapy with PEG-interferon α2a and ribavirin for chronic hepatitis C virus infection. His clinical course, neurological findings, and his electromyogram results were all consistent with acute inflammatory demyelinating polyneuropathy. Our patient recovered completely after interferon was stopped and symptomatic treatment and a further electromyogram showed a disappearance of neuropathy. Four weeks later, PEG-interferon α2a was reintroduced with a gradually increasing dose without any reappearance of neurological symptoms allowing hepatitis C seroconversion.

Conclusions: Recognition of this rare yet possible presentation is important for early and accurate diagnosis and treatment. This case report also suggests that the reintroduction of PEGylated interferon in patients who had presented with acute inflammatory demyelinating polyneuropathy related to interferon α may be safe, but this must be confirmed by further studies.
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http://dx.doi.org/10.1186/1752-1947-6-278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459811PMC
September 2012

Pseudoachalasia secondary to metastatic breast carcinoma mimicking radiation stenosis.

Clin Res Hepatol Gastroenterol 2012 Dec 4;36(6):e117-21. Epub 2012 Jul 4.

Department of hepato-gastroenterology, Hassan II university hospital Fes, Fes, Morocco.

We reported on a rare case of pseudoachalasia secondary to metastatic breast carcinoma mimicking radiation stenosis. A 65-year-old woman was admitted to our department complaining of progressive dysphagia to solids and liquids. Her medical history revealed a surgery for left breast tumour, which had been performed 11 years, previously, with adjuvant treatment based on hormonal therapy and radiotherapy. The presenting symptoms had started 1 year before her admission, with progressive paradoxical medio chest dysphagia. The patient had lost 7 kg in weight without prominent anorexia. The endoscopic, radiological, histological and manometric appearance was in favor pseudoachalasia associated with stenosis of the esophagus. The esophageal mucosa covering the lumen of the stricture after the dilation was smooth and neoplasm was not detected by another repeated biopsy. We could not obtain the diagnosis for the stricture. The most likely diagnosis was a pseudoachalasia associated with esophagus stenosis complicating probably radiotherapy. The patient had received four pneumatic dilatations with several normal biopsies. At the last one (4 months later), pathological examination of the biopsy specimen revealed infiltrating lobular breast carcinoma. The final diagnosis was pseudoachalasia secondary to metastatic breast carcinoma mimicking radiation stenosis. Treatment was based mainly on tamoxifen.
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http://dx.doi.org/10.1016/j.clinre.2012.05.016DOI Listing
December 2012

Mutation analysis of BRAF exon 15 and KRAS codons 12 and 13 in Moroccan patients with colorectal cancer.

Int J Biol Markers 2010 Oct-Dec;25(4):179-84

Laboratoire de Biologie des Cancers, Equipe Micro-organismes et Facteurs Oncogènes, Faculté de Médecine et de Pharmacie, Fez, Morocco.

Background: The RAS/RAF/MEK/MAP kinase cascade transduces signals from the cell surface to the nucleus in order to control cellular responses including proliferation, differentiation and survival. We investigated the occurrence of BRAF exon 15 and KRAS codon 12 and 13 mutations in Moroccan patients with colorectal cancer.

Methods: Sixty-two samples from patients with sporadic colorectal adenocarcinomas were studied for BRAF exon 15 and KRAS codon 12 and 13 mutations. DNA from paraffin-embedded tissue specimens was analyzed by a combination of polymerase chain reaction-high resolution melting and direct sequencing.

Results: Of the analyzed specimens, 29% exhibited KRAS codon 12 or 13 mutations and only 1.6% carried a BRAF codon 600 mutation. KRAS mutations were more often observed in women (35.5%) than in men (22.6%). Patients in the age range between 41 and 60 years were more likely to be carriers of this mutation. No KRAS mutations were detected in patients aged >60 years.

Conclusion: Despite the limited study sample, our data suggest that KRAS mutations arise more frequently than BRAF mutations in Moroccan patients with colorectal carcinomas. The KRAS mutation status must be assessed in a large cohort of Moroccan patients to confirm these findings and to determine whether this mutation in combination with extrinsic, environmental or microenvironmental factors might be involved in the high frequency of colorectal cancer in middle-aged Moroccans.
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April 2011
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