[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) is characterized by widespread epidemiological and molecular heterogeneity. Previous work showed that in the western part of North Africa, a region of low incidence of HCC, mutations are scarce for this tumor type. As epigenetic changes are considered possible surrogates to mutations in human cancers, we decided, thus, to characterize DNA methylation in HCC from North-African patients.
A set of 11 loci was investigated in a series of 45 tumor specimens using methylation-specific and combined-bisulfite restriction assay PCR. Results obtained on clinical samples were subsequently validated in liver cancer cell lines.
DNA methylation at tumor suppressor loci is significantly higher in samples displaying chromosome instability. More importantly, DNA methylation was significantly higher in Arg/Arg when compared to Pro/Pro genotype carriers at codon 72 rs1042522 of TP53 (65% vs 20% methylated loci, p = 0.0006), a polymorphism already known to affect somatic mutation rate in human carcinomas. In vitro experiments in cell lines indicated that enzymes controlling DNA methylation were differentially regulated by codon 72 Arg or Pro isoforms of p53. Furthermore, the Arg72-carrying version of p53 was shown to re-methylate DNA more rapidly than the pro-harboring isoform. Finally, Pro-carrying cell lines were shown to be significantly more resistant to decitabine treatment (two-fold, p = 0.005).
Our data suggest that Arg72Pro polymorphism in a WT p53 context may act as a primary driver of epigenetic changes in HCC. It suggests, in addition, that rs1042522 genotype may predict sensitivity to epigenetic-targeted therapy. This model of liver tumorigenesis that associates low penetrance genetic predisposition to epigenetic changes emerges from a region of low HCC incidence and it may, therefore, apply essentially to population living in similar areas. Surveys on populations submitted to highly mutagenic conditions as perinatally-acquired chronic hepatitis B or aflatoxin B1 exposure remained to be conducted to validate our observations as a general model.
[Show abstract][Hide abstract] ABSTRACT: Hepatitis B virus (HBV) is one of the most common human pathogens that cause aggressive hepatitis and advanced liver disease (AdLD), including liver cirrhosis and Hepatocellular Carcinoma. The persistence of active HBV replication and liver damage after the loss of hepatitis B e antigen (HBeAg) has been frequently associated with mutations in the pre-core (pre-C) and core promoter (CP) regions of HBV genome that abolish or reduce HBeAg expression. The purpose of this study was to assess the prevalence of pre-C and CP mutations and their impact on the subsequent course of liver disease in Morocco.
A cohort of 186 patients with HBeAg-negative chronic HBV infection was studied (81 inactive carriers, 69 with active chronic hepatitis, 36 with AdLD). Pre-C and CP mutations were analyzed by PCR-direct sequencing method. The pre-C stop codon G1896A mutation was the most frequent (83.9%) and was associated with a lower risk of AdLD development (OR, 0.4; 95% CI, 0.15-1.04; p = 0.04). HBV-DNA levels in patients with G1896A were not significantly different from the other patients carrying wild-type strains (p = 0.84). CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were associated with higher HBV-DNA level and increased liver disease severity. Multiple logistic regression analysis showed that older age (≥ 40 years), male sex, high viral load (>4.3 log(10) IU/mL) and CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were independent risk factors for AdLD development. Combination of these mutations was significantly associated with AdLD (OR, 7.52; 95% CI, 4.8-8; p<0.0001).
This study shows for the first time the association of HBV viral load and CP mutations with the severity of liver disease in Moroccan HBV chronic carriers. The examination of CP mutations alone or in combination could be helpful for prediction of the clinical outcome.
[Show abstract][Hide abstract] ABSTRACT: Background and aims:
Hepatocellular carcinoma (HCC) is a common cause of death by cancer worldwide. In Morocco, HCC is characterized by few mutations and a mild chromosome instability suggesting that epigenetic changes may represent the driving force of tumorigenesis in the region. Recently, three studies looked for an association between EP300 or PCAF polymorphisms and cancer but there is a conspicuous lack of data regarding these histone acetyltransferase (HAT) variants and HCC development. The aim of the current study was to assess the impact of the Ile997Val in EP300 and Asn386Ser in PCAF polymorphisms on the risk of HCC.
Materials and methods:
We performed a case-control study comparing 94 cases with HCC and 220 matching controls. Sequencing methods were used to determine the genotype at the Ile997Val and Asn386Ser on EP300 and PCAF.
We found an overall association between genotypes Val/Val in EP300 and HCC risk (OR, 3.03; 95% CI, 1.08-8.47; P=0.028). Population stratifications revealed a trend or significantly higher risks of HCC development for women and HCV-negative patients carrying the EP300 Val/Val genotype (OR, 4.06; 95% CI, 0.71-23.36; P=0.09 and OR, 4.48; 95% CI, 1.04-19.14; P=0.02, respectively). The PCAF Ser/Ser genotype at codon 386 was more frequent in HCC cases than in control group (P=0.03). We observed trends for higher risk of HCC among men and/or HCV-negative patients carrying Ser/Ser genotype when compared with controls (OR, 10.62; 95% CI, 0.50-225.13 and OR, 11.78; 95% CI, 0.47-295.56, respectively).
It appears that variants of the transcriptional coactivator genes (EP300 and PCAF) may influence HCC risk in populations with low mutations or chromosomal instability rates. Additional surveys are warranted to confirm this first report.
No preview · Article · Jun 2012 · Cancer Epidemiology
[Show abstract][Hide abstract] ABSTRACT: The implication of hemochromatosis (HFE) gene mutations in chronic viral hepatitis remains controversial. The aim of the present study was to measure the frequencies of the common HFE gene mutations in Moroccan subjects with chronic viral hepatitis B and C and to assess their influence on the progression of liver disease. H63D and C282Y mutations were screened by the polymerase chain reaction followed by restriction fragment length polymorphism analysis in 170 chronic hepatitis B patients, 168 chronic hepatitis C patients, and 200 healthy controls. A very small proportion of patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV; 1.8% and none, respectively) were heterozygous for the C282Y mutation, that is, rates not statistically different from those observed in healthy control (2%, P > 0.05). Similarly, the frequency of the H63D allele was not significantly different between HBV (13.8%) or HCV (14.3%) patients and controls (13.5%, P > 0.05). Multivariate analysis showed that carriers of the H63D mutation infected with HBV are at higher risk to progress towards an advanced liver disease when compared with patients infected with HBV with wild-type (OR = 2.45, 95% CI = 1.07-5.58). In contrast, no association between HFE mutated HCV-infected patients and an increased risk of disease progression was found (OR = 1.24, 95% CI = 0.61-2.50, P = 0.547). In conclusion, in Morocco the frequency of the HFE C282Y allele is very low and H63D mutation carriage occurs in almost 14% of the patients, a rate similar in chronic hepatitis patients and healthy controls. In the case of chronic hepatitis B, the carriage of the H63D variant represents a risk factor of evolution towards a more active disease.
Full-text · Article · Dec 2011 · Journal of Medical Virology
[Show abstract][Hide abstract] ABSTRACT: Single-nucleotide polymorphisms (SNPs) in codon 72 of the TP53 gene (rs1042522) and in the promoter region of the MDM2 gene (SNP309; rs2279744) have been shown to play a role in the predisposition to many cancers. However, these findings were inconsistent in other tumor types, and ethnicity is suspected to be a critical factor influencing the effects of these SNPs on the cancer risk. The aim of the present study was to investigate whether these functional SNPs were associated with an enhanced risk of liver tumorigenesis in Moroccan patients. We have genotyped both polymorphisms in 96 patients with hepatocellular carcinoma (HCC) and 222 controls without HCC matched for age, gender and ethnicity by PCR-RFLP confirmed by sequencing. A joint effect between the MDM2 and TP53 polymorphisms and an increased risk of liver cancer was detected, with the odds ratio for the presence of both MDM2 309GG and TP53 72Pro/Pro genotypes being 10 (95% confidence interval 0.39-255.55). Interestingly, a significant increase in the HCC risk was observed when at least two deleterious alleles were present, indicating an allele dosage effect. There was no evidence for any association with early age of HCC onset when deleterious alleles of MDM2 SNP309 and TP53 Arg72Pro where present. Our findings suggest that the combination of TP53 72Pro and MDM2 309G polymorphisms enhance the risk of developing HCC. These results deserve further confirmation in other populations.
No preview · Article · Oct 2011 · The International journal of biological markers
[Show abstract][Hide abstract] ABSTRACT: The implication of haemochromatosis (HFE) gene mutations in chronic viral hepatitis remains controversial. The aim of the present study was to assess the frequencies of the common haemochromatosis gene mutations in Moroccan subjects with chronic viral hepatitis B and C. H63D and C282Y mutations were screened by using polymerase chain reaction followed by restriction fragment length polymorphism analysis in 170 chronic hepatitis B patients, 168 chronic hepatitis C patients and 200 healthy controls. The distribution of allele frequency was then compared between different groups of patients. No subject homozygous for the C282Y mutation was found while 1.76% and 0% were heterozygous for this mutation in HBV and HCV patients, that is, rates not statistically different from those observed in healthy control (2%, 0.129< p<1.000). Similarly, the frequency of the H63D allele was not significantly different between HBV (13.8%) or HCV (14.3%) patients and controls (13.5%, 0.60< p<0.89). Although they do not reach the significance threshold, serum ferritin levels, indicative of body iron content, were higher in HBV or HCV patients than in control individuals with HFE mutations (110.7±43.61 and 149.67±43.52 ng/ml respectively vs 80.84±21.38 ng/ml, 0.229< p<0.607). In conclusion, in Morocco the frequency of the HFE C282Y allele is very low and H63D mutation carriage occurs in <14% of the subjects, a rate similar in chronic hepatitis patients and control individuals. Thus, we assume that the carriage of the common HFE mutations does not represent a risk factor for evolution towards chronic hepatitis B or C in the genetic and environmental context of North Africa.
Full-text · Article · Sep 2011 · Journal of epidemiology and community health
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the prevalence of Hepatitis B Virus (HBV) genotypes, subgenotypes, HBV surface antigen (HBsAg) subtypes and naturally occurring mutations in Major Hydrophilic region (MHR) of HBsAg among Moroccan patients with chronic HBV infection.
The study included 200 patients chronically infected with HBV. The HBV genotypes, subgenotypes, HBsAg subtypes and MHR variants were determined by direct sequencing of the HBV surface (S) gene and phylogenetic analysis.
The S gene was successfully amplified in 134 patients. The mean age was 40.6 ± 12.2 years. Genotype D was predominant (90%, 120/134) and genotype A was less frequent (10%, 14/134). Genotype D strains belonged to subgenotypes D7 (70.8%, 85/120), D1 (25.8%, 31/120) and D2 (0.9%, 1/120). Three strains (2.5%) could not be classified in any subgenotype of genotype D. All genotype A strains belonged to subgenotype A2. HBsAg subtypes found were ayw2 (82.1%, 110/134), adw2 (10.4%, 14/134), ayw3 (3%, 4/134) and ayw4 (3%, 4/134). The global prevalence of MHR variants was 15% (20/134) with substitution P120T/S the most frequent (3.7%, 5/134). The occurrence of MHR variants was significantly associated with advancing age (>40 years) (p = 0.003) and independent of sex, HBeAg status, viral load, genotype, subgenotype and HBsAg subtype.
This study provides the first description of predominance of HBV subgenotype D7/subtype ayw2 among Moroccan HBV chronic carriers. It also showed a significant prevalence of naturally occurring MHR variants in Morocco.
Full-text · Article · May 2011 · The Journal of infection
[Show abstract][Hide abstract] ABSTRACT: Reactive oxygen species have been related to the aetiology of cancer as they are known to be mitogenic and therefore capable of tumour promotion. The aim of this study was to assess the role of common variation in three polymorphic genes (MnSOD Ala-9Val, GPX1 Pro198Leu and CAT -262 C > T) coding for antioxidant defence enzymes in modulating individual susceptibility to hepatocellular carcinoma (HCC) using a case-control study (cases = 96 and controls = 222). PCR-RFLP and sequencing methods were used to determine the genotype. Overall, there were no associations between genotypes GPX1 and HCC risk (OR, 1.16; 95% CI, 0.56-2.42; p = 0.685). The MnSOD Ala/Ala and CAT TT genotypes were more frequent in HCC than in control (p = 0.001 and p = 0.072, respectively). Further analyses stratified by gender or HCV infection revealed that men and HCV-infected patients carrying CAT TT genotype had a higher risk to develop HCC when compared with controls (OR = 15.94; 95% CI, 3.48-72.92; p < 0.000001 and 12.01; 95% CI, 0.64-223.63, p = 0.056, respectively). Combined MnSOD Ala/Ala and GPx1 Leu/Leu had a synergistic effect on HCC risk, with an OR of 3.84 (p = 0.029). Furthermore an even more pronounced risk was observed when we combined MnSOD Ala/Ala and CAT TT (OR = 13.60, p = 0.023). It appears that variants in MnSOD, CAT or GPX1 have an influence on HCC risk in this cohort. Furthermore, it is possible that cumulative defects in protection from oxidative stress may result in increased risk of liver cancer in the Moroccan population.
Full-text · Article · Nov 2009 · Free Radical Research
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma is a major malignant tumor characterized in all areas by the disparity of risk between genders. The molecular bases of such disparity are still poorly understood. DNA-methyltransferase-3B (DNMT3B) may play an oncogenic role during tumorigenesis, and its genetic variants have been consistently associated with risk of several cancers, but a single study has investigated their roles in hepatocellular carcinoma (HCC). Polymorphisms of the DNMT3B gene may influence its activity on DNA methylation in several cancers, thereby modulating susceptibility to tumorigenesis. To test this hypothesis, we investigated the association between single nucleotide polymorphism -149C>T (rs2424913) in the promoter region DNMT3B and risk of HCC in a Moroccan population. In this case-control study, the DNMT3B SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism in 96 HCCs patients and 222 healthy controls that matched for age, sex and ethnicity. Overall, we found that, the DNMT3B 149 TT genotype was not significantly associated with increased risk of HCC (adjusted odds ratio (OR), 0.86, 95% CI, 0.41-1.80, P=0.697). Stratification analysis detected, however, a trend towards a profound risk in the female subset of patients (OR=2.04, 95% CI, 0.77-5.42) and a lesser risk for HCV-infected patients (OR=1.33, 95% CI, 0.43-4.17). Our findings contrast with those of previous studies performed in various cancers, which showed that individuals carrying at least one T allele have a significantly increased risk of developing cancer. In addition, we provide genetic evidence for the major difference of HCC risk between men and women. Further mechanistic studies are needed to unravel the underlying molecular mechanisms.
Full-text · Article · May 2009 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
[Show abstract][Hide abstract] ABSTRACT: The Murine double minute 2 (MDM2) gene encodes a negative regulator of the p53 tumor suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumor formation. The aim of this study was to investigate whether this functional SNP is associated with an enhanced risk of liver tumorigenesis in Moroccan patients.
The study consisted in the comparison of 96 hepatocellular carcinomas (HCC) cases and 222 controls without HCC matched for age, gender and ethnicity. PCR-RFLP and sequencing methods were used to determine the genotype at the MDM2 SNP309T>G locus.
Overall, our results indicate that the GG genotype of SNP309 is significantly associated with an increased risk of HCC (odds ratio, OR=2.60, 95% CI, 1.08-6.28). Interestingly, despite a wide range of confidence interval, there is a trend associating the GG genotype with a high risk of HCC in males (OR=3.31; 95% CI, 0.93-11.82) and in HCV-infected patients (OR=3.7; 95% CI, 0.82-16.45). By contrast, no association between age at diagnosis and MDM2 SNP309 genotypes was observed in HCC patients (P=0.610).
Our findings suggest that the MDM2 309T>G polymorphism is an important modulator of hepatocellular carcinoma development in Moroccan patients.
Full-text · Article · Mar 2009 · Cancer Detection and Prevention
[Show abstract][Hide abstract] ABSTRACT: Hereditary hemochromatosis and SERPINA1 mutation were reported to affect liver functions. Our objective was to estimate the prevalence of HFE and SERPINA1 (formerly known as alpha1-antitrypsin, AAT) mutations and assess their influence on hepatocellular carcinoma development.
This study included 222 controls and 96 cases with hepatocellular carcinoma. PCR-RFLP was used to characterize S and Z alleles in SERPINA1, as well as C282Y/H63D alleles of HFE.
In healthy subjects and hepatocellular carcinoma patients as well, no homozygotes for the C282Y mutation were found. In controls, heterozygosity and homozygosity for the H63D mutation were 27 and 0.9%, respectively. Among patients, homozygosity for the H63D mutation was 3.1%, whereas heterozygosity for C282Y and H63D was 2.1 and 35.4%, respectively. Interestingly, albeit it does not reach significance (p=0.062), H63D was more prevalent in hepatocellular carcinoma patients than in controls (38.5 vs. 27.9%, respectively). The association was stronger when considering only male patients with hepatocellular carcinoma (47.1 vs. 23.6, p=0.001). Allele frequencies of S and Z in controls were 0.45% (95% CI=0.2-1.07) and 0.22% (95% CI=0.2-0.6), respectively, and 1 for S and 0% for Z in HCC. No significant difference was found between cases and controls.
We provide a novel appraisal of HFE and SERPINA1 mutations prevalence in the Moroccan population. Results are consistent with the worldwide spread of the H63D and S mutation and the north European restriction of the C282Y and Z. Our results show that H63D carriage is increased among hepatocellular carcinoma patients, suggesting that it may confer an increased susceptibility to hepatocellular carcinoma even in a heterozygous state. On the contrary, HFE C282Y and SERPINA1 mutations do not contribute to hepatocellular carcinoma development.
Full-text · Article · Mar 2008 · Archives of Medical Research
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide. The main risk factors for its development are hepatitis B and C virus infections. Hepatitis B and C viruses induce chronic inflammation and oxidative stress that could predispose a cell to mutagenesis and proliferation. Manganese superoxide dismutase (MnSOD) catalyses the detoxification of free radicals, thus playing a crucial role in the protection against damage. A valine (Val) to alanine (Ala) substitution at amino acid 9, mapping within the mitochondrion-targeting sequence of the MnSOD gene, has been associated with an increased cancer risk. The aim of our study was to investigate a possible association of the Val/Ala-MnSOD polymorphism and HCC development in Moroccan patients. Genotypes were determined by means of PCR and RFLP analysis in 96 patients with HCC and 222 control subjects matched for age, sex, and ethnicity. Homozygous Ala/Ala carriers were 31% in the cases and 18% in the controls, which corresponds to an odds ratio (OR) of 2.89, with a 95% confidence interval (CI) of 1.47-5.68. Stratification into subgroups based on HCV infection status revealed an even more increased risk for homozygous Ala/Ala carriers with hepatitis C infection (38.2% in the cases versus 14.8% in the control subjects OR, 5.09; 95% CI, 1.76-14.66). Our findings provide further evidence of an association between the Ala-9Val MnSOD polymorphism and HCC occurrence in hepatitis C virus-infected Moroccan patients.
Full-text · Article · Feb 2008 · Mutation Research/Genetic Toxicology and Environmental Mutagenesis
[Show abstract][Hide abstract] ABSTRACT: Aim: Codon 72 polymorphism of the p53 gene has been implicated in cancer risk, and it has been suggested that it may have an impact on the clinical outcome of the disease. Our objective was to evaluate the association between p53 polymorphism at codon 72 and hepatocellular carcinoma (HCC) in the Moroccan population.
Methods: Genomic DNA was extracted from peripheral blood cells of 96 patients with HCC and 222 controls without HCC matched for age, gender and ethnicity. Codon 72 polymorphism of p53 was identified by PCR-restriction fragment length polymorphism, confirmed by sequencing.
Results: Patients with HCC had higher frequencies of Pro/Pro (13.5% vs. 6.3%, P < 0.02) than controls and consequently a 2.3-fold increased risk of liver cancer development (odds ratio [OR], 2.304; 95% confidence interval [CI], 1.014–5.234). In addition, we found a significant association between the p53Arg72Pro polymorphism and the female gender in HCC. Men with Pro/Pro genotype had a 1.57-fold increased risk for HCC, whereas the corresponding genotype in women had a 4.4-fold increased risk of HCC (OR, 4.4; 95% CI, 1.18–16.42). No correlation between the polymorphism and HCC risk was found when comparing the hepatitis C virus (HCV)-positive cases to HCV-positive controls. However, HCV-negative subjects and Pro/Pro genotype had a 3.31-fold increased risk for HCC.
Conclusion: These results provide evidence that p53 polymorphism at codon 72 is a modifier of hepatocarcinogenesis, especially in women and HCV-negative subjects.
Full-text · Article · Sep 2007 · Hepatology Research
[Show abstract][Hide abstract] ABSTRACT: IntroductionLes tumeurs stromales (GIST pour gastrointestinal stromal tumors) sont les tumeurs conjonctives les plus fréquentes du tube
digestif. Elles s’intègrent désormais dans un cadre nosologique précis défini par la positivité au CD117 en immunohistochimie.
Nous rapportons et analysons une série de 17 GIST opérées à la Clinique chirurgicale « A » (Rabat, Maroc) entre mars 1999
et mars 2005.
Matériel et méthodesNous avons inclus rétrospectivement les GIST confirmées à l’examen histologique ayant comporté obligatoirement une étude immunohistochimique.
Les données démographiques, cliniques, histologiques et thérapeutiques des patients ont été analysées.
RésultatsNous avons colligé 17 cas de GIST, 8 hommes et 9 femmes. L’âge moyen était de 57 ans (extrêmes: 20–75 ans). Les localisations
tumorales étaient l’estomac (n = 12) et l’intestin grêle (n = 3) puis l’œsophage (n = 1) et le rectum (n = 1). Chez 16 patients,
le traitement à visée curative a consisté en une résection chirurgicale de première intention, adaptée à la localisation tumorale,
sans curage ganglionnaire systématique, avec une métastasectomie hépatique dans un cas. La tumeur a été jugée inextirpable
à l’exploration chirurgicale chez une patiente. La résection tumorale a été réalisée par voie cœlioscopique dans un cas. La
mortalité opératoire était nulle. Les suites opératoires immédiates étaient simples à l’exception d’une éviscération libre
traitée au onzième jour postopératoire. Le délai moyen de suivi était de 9 mois (extrêmes : 1–40 mois). Huit patients étaient
vivants sans récidive. Une patiente ayant développé, après 8 mois des métastases hépatiques et péritonéales a été traitée
par imatinib avec une régression des lésions. Un patient en récidive locale (œsophage) est décédé après 17 mois de survie
globale. Sept patients ont été perdus de vue dont un ayant développé des métastases hépatiques.
ConclusionLe potentiel évolutif de ces tumeurs reste difficile à évaluer, faute de critères histopronostiques fiables. Le devenir au
long cours de nos patients opérés pour GIST doit faire l’objet d’une évaluation rapprochée et régulière en vue d’un dépistage
précoce des récidives et pour établir dans un cadre prospectif les facteurs prédictifs de récidive. La chirurgie large et
complète reste, dans les régions du monde où l’imatinib ne peut être distribué, la seule arme thérapeutique efficace.
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the digestive tract, now defined by the immunohistochemical
expression of CD117. We report 17 cases of GIST operated between March 1999 and March 2005 in The Clinique chirurgicale «
A » of Rabat (Morocco).
Methodswe have retrospectively included GIST confirmed by histopathological and immunohistochemical examination. Demographic, clinical,
pathological and treatment data were analysed.
Resultsseventeen patients with GIST were operated: 8 men and 9 women. The mean age was 57 years (20–75). Tumours were located in
the stomach (n = 12), small intestine (n = 3), oesophagus (n = 1) and rectum (n = 1). Sixteen patients underwent a curative
resection adapted to the location, without systematic lymphadenectomy. A patient underwent a hepatic metastasectomy. Resection
was not possible in one patient. The mean follow-up was 9 months (1–40). Eight patients were living without recurrence. A
patient who had developed liver and peritoneum metastasis was treated by imatinib with good result. A patient operated for
oesophagus GIST developed a local recurrence and died 17 months after operation. Seven patients were not followed up, one
with liver metastasis.
ConclusionGIST evolution is hard to predict. Close follow-up of our patients would help us to identify and treat recurrence earlier
and determine local patterns of tumour recurrence. Complete and wide surgical resection remains the only efficient treatment
in regions where imatinib is not available.
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the digestive tract, now defined by the immunohistochemical expression of CD117. We report 17 cases of GIST operated between March 1999 and March 2005 in The Clinique chirurgicale «A» of Rabat (Morocco). Methods: we have retrospectively included GIST confirmed by histopathological and immunohistochemical examination. Demographic, clinical, pathological and treatment data were analysed. Results: seventeen patients with GIST were operated: 8 men and 9 women. The mean age was 57 years (20-75). Tumours were located in the stomach (n = 12), small intestine (n = 3), oesophagus (n = 1) and rectum (n = 1). Sixteen patients underwent a curative resection adapted to the location, without systematic lymphadenectomy. A patient underwent a hepatic melastasectomy. Resection was not possible in one patient. The mean follow-up was 9 months (1-40). Eight patients were living without recurrence. A patient who had developed liver and peritoneum metastasis was treated by imatinib with good result. A patient operated for oesophagus GIST developed a local recurrence and died 17 months after operation. Seven patients were not followed up, one with liver metastasis. Conclusion: GIST evolution is hard to predict. Close follow-up of our patients would help us to identify and treat recurrence earlier and determine local patterns of tumour recurrence. Complete and wide surgical resection remains the only efficient treatment in regions where imatinib is not available.
[Show abstract][Hide abstract] ABSTRACT: Au Maroc, la mise sur le marché des anti-inflammatoires non stéroïdiens (AINS) inhibiteurs sélectifs de la cyclooxygénase 2 (coxibs) a motivé la mise en place d’une étude dont l’objectif principal est d’évaluer les effets gastro-intestinaux majeurs liés à la prise des AINS, puis par la suite de comparer la tolérance digestive des AINS classiques avec celle des coxibs. Matériel et méthode : il s’agit d’une étude prospective observationnelle entre avril 2001 et mai 2002. Elle s’est déroulée auprès des gastro-entérologues du CHU, du secteur public et privé de Rabat, ainsi qu’au niveau des urgences chirurgicales du CHU de Rabat. Résultats : sur une période de 14 mois, 123 patients porteurs d’une atteinte gastro-intestinale majeure coïncidant avec la prise d’un AINS ont été colligés. Le sexe masculin est prédominant et l’âge moyen est de 49,45 ± 14,3 ans. Pour 63 % d’entre eux, il s’agissait d’ulcères compliqués d’hémorragie ou de perforation. Les ulcères gastriques ont représenté les principales lésions mises en évidence par l’exploration endoscopique (45 %). Au niveau des services d’urgences, la prévalence des hémorragies digestives hautes liées à la prise d’AINS parmi l’ensemble des hémorragies digestives hautes, toutes causes confondues, a été évaluée à 8,7 %. La prévalence des perforations d’ulcères sous AINS est de 9,3 %. L’AINS le plus incriminé a été l’aspirine, le délai d’apparition des lésions a été inférieur à 1 mois dans 56 % des cas. Conclusion : à travers notre étude, nous avons pu relever certaines particularités propres à la population étudiée telles que la prédominance masculine et la vulnérabilité du sujet jeune. Par ailleurs, nous avons retrouvé un grand nombre de facteurs de risques validés dans la littérature à savoir : les antécédents digestifs et rhumatologiques, le délai d’apparition de la symptomatologie inférieur à 1 mois, l’association des AINS à l’aspirine, le terrain diabétique et hypertendu. Cependant, aucune conclusion n’a pu être faite quant à la meilleure tolérance digestive des coxibs vu le faible nombre de patients dans notre série soumis à ce type d’AINS.
Mots-clés : gastro-entérologie, ulcère, anti-inflammatoire, Maroc
[Show abstract][Hide abstract] ABSTRACT: In Morocco, the need for post-marketing surveillance of selective Cox2 inhibitors (coxibs) prompted a study to assess the serious gastrointestinal effects of NSAIDs and to compare gastrointestinal tolerance of conventional NSAIDs and coxibs. A prospective study was conducted from April 2001 through May 2002 among hospital-staff gastroenterologists in the public and private sector as well as emergency surgical units. Over this period, 123 patients were reported to have serious NSAID-related gastrointestinal effects, and 63% of them were admitted for bleeding or perforated ulcers. Endoscopy most often identified the lesion as a gastric ulcer (45%). Emergency rooms reported that aspirin was the most common causal agent and that NSAIDs accounted for 8.7% of bleeding and 9.3% of the perforated ulcers. Our findings indicate that men and youth are most vulnerable to serious gastrointestinal effects from these drugs. Several risk factors from the literature were confirmed in our population: history of gastrointestinal disorders and joint disease, occurrence within less than 1 month of beginning the drug; association of NSAIDs and aspirin, diabetes and hypertension. No conclusion could be drawn about the comparative gastrointestinal tolerance of conventional NSAIDs and coxibs, however, since the latter account for only 3% of the NSAID market.