Epidemiological insights into colorectal cancer in northwestern Algeria.

Objectives: The incidence of colorectal cancer (CRC) has exhibited regional variability in North Africa and the Middle East, with a steady increase in Algeria. Despite this trend, limited data exist on the epidemiology of CRC in northwestern Algeria. Our study aimed to investigate the epidemiological characteristics of CRC in this region. Methods: We conducted a retrospective study examining 255 confirmed CRC cases through medical records from patients at the Sidi Bel Abbes anti-cancer centre. Results: The mean age of the study participants was 59 ± 13 years. The results showed a higher incidence in males (57%) than in females, and colon (62%) than rectal cancer. Within this cohort, 47% had a pre-existing medical condition, while 39% had a family history of cancer. Adenocarcinomas were the prevailing histological subtype in 94% of CRC cases. Compared with colon cancer, rectal cancer was less often diagnosed at stage IV of the disease (OR = 0.75; 95% CI = 0.09, 4.86; p = 0.8) and more likely in early-onset patients (OR = 2.27; 95% CI = 1.25, 4.17; p = 0.007). Men were at a higher risk of being diagnosed with metastatic CRC primarily hepatic metastases (OR = 2.03; 95% CI = 1.07, 3.99; p = 0.033) and pulmonary metastases (OR = 2.50; 95% CI = 1.07, 6.59; p = 0.045). Conclusion: This study may provide a comprehensive glimpse into CRC epidemiology in northwest Algeria. Understanding regional differences is the key to implementing specific preventive and interventional strategies.

Cytogenetic landscape in 1012 newly diagnosed chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) stratification mainly relies on FISH markers according to Döhner's hierarchical model which includes high-risk FISH markers, intermediate FISH, or low-risk FISH. Recently, complex karyotype (CK) has been demonstrated as an independent negative prognostic factor in CLL. METHODS: A series of 1012 untreated CLL patients have been investigated with both FISH and chromosome banding analysis (CBA) on the same pellet obtained from interleukin IL-2-CPG DSP30 oligonucleotide-stimulated cultured cells. RESULTS: Combining both FISH and CBA has led to refine prognostic categories with identification of 30% of CK in low-risk and intermediate FISH group. This raises the issue of switching them to a high-risk group. While this series confirmed the significant association between CK and high-risk FISH (P = .003), 33% of CK present no ATM or TP53 deletion. Three groups characterized by significant association between FISH markers and CBA have emerged: CK with TP53 loss and monosomy 15; CK with ATM loss and 14q32 translocation; and CK without ATM or TP53 losses but trisomies 12, 18, and 19 or t(14;18)(q32;q21). CONCLUSION: We have observed that in addition to FISH analysis, the CBA allows detection of many abnormalities with potential impact on patient follow-up and treatment, mainly CK.

Epidemiological, clinical and pronostic aspects of multiple myeloma eligible for therapeutic intensification followed by autologous hematopoietic stem cell in the Algerian West: report of 147 cases.

BACKGROUND: Multiple Myeloma (MM) represent about 1 to 2% of cancers and 15% of all hematological malignancies. It is characterized by malignant proliferation of plasmocytes in bone marrow and an excess of secreted monoclonal immunoglobulins (Ig) Objective: Describe the epidemiological, clinical, biological and prognosis of patients with MM treated with autologous peripheral hematopoietic stem cell transplantation (APHSCT) in the Algerian West. METHODS: It is a retrospective descriptive study covering all MM patients treated with APHSCT over a period of 7 years (2008-2015) at service of Haematology and Cell Therapy of the EHU "1er November 1954 of Oran, Algeria. RESULTS: During the study, we collected 147 MM patients treated with APHSCT. The median age of the population was 53 years with a male predominance and a sex ratio of 1.53. Clinically, bone syndrome was found in 75.51% of cases. Paraclinaclly, anemia was found in 78.52% of patients, hyperprotidemy in 59.06%. A monoclonal peak in serum protein electrophoresis was noted in 80.54% of cases. Isotype repartition was: IgG (61.04%), IgA (19.17%), monoclonal light chains (16.11%). A plasmocytosis more than 10% was detected in 89.79% of cases. According to the Durie and Salmon classification, all of our patients were classified as stage III. The average survival time was thirty months. CONCLUSION: The majority of our patients had advanced stage of MM to the presentation and the median survival was not reached thus emphasizing a high rate of remission and marks an important advance in the care of MM in Algeria.

Increased Gustatory Response Score in Obesity and Association Levels with IL-6 and Leptin.

Background. The aim of this study was to investigate the relationship between the circulating IL-6 and leptin levels with taste alteration in young obese patients. Methods. A retrospective case-control study was conducted in thirty obese patients and thirty age- and sex-matched healthy controls. Results. Circulating levels of IL-6 and leptin were significantly increased in obese patients than in controls. However, catalase and ORAC levels were significantly decreased in obese patients compared to controls. Additionally, obese participants had high scores for the detection of fats (gustatory response scores [GRS]; p < 0.001). Moreover, IL-6 and leptin were strongly associated with GRS alteration among patients with GRS 4 (resp., OR =17.5 [95% CI, 1.56-193.32; p = 0.007]; OR = 16 [95% CI, 1.69-151.11; p = 0.006]). For the Mantel-Haenszel common odds ratio estimate (MH OR), IL-6 and leptin were strongly associated with obesity, in patients with either GRS 4 or GRS > 4 (resp., MH OR = 8.77 [95% CI, 2.06-37.44; p = 0.003]; MH OR = 5.76 [95% CI, 1.64-20.24; p = 0.006]). Conclusions. In a low grade inflammation linked to obesity, taste alteration is associated with high levels of IL-6 and leptin.

Effect of IL-1ß and IL-1RN polymorphisms in carcinogenesis of the gastric mucosa in patients infected with Helicobacter pylori in Algeria.

BACKGROUND: Infection with Helicobacter pylori is considered a potential risk of developing gastric cancer in association with contributing host genetic factor. IL-1ß and IL-1RN polymorphisms appear to maintain and promote Helicobacter pylori infection and to stimulate neoplastic growth of the gastric mucosa. OBJECTIVE AND METHODS: In order to elucidate the effect of these polymorphisms in combination with gastric cancer in a population from northwestern Algeria, a case-control study was carried out on 79 patients infected with H. pylori with chronic atrophic gastritis and/or gastric carcinoma, and 32 subjects were recruited as case-control. IL-1ß-31 bi-allelic and IL-1ß-511 bi-allelic polymorphisms and IL-1RN penta-allelic were genotyped. RESULTS: IL-1ß-31C was associated with an increased risk of developing gastric carcinoma (OR=4.614 [1.43-14.81], p=0.01). However, IL-1RN2 heterozygous allele type was significantly associated with chronic atrophic gastritis (OR=4.2 [1.23-3.61], p=0.022). IL-1ß-511T was associated with an increased risk of development of chronic atrophic gastritis (OR=4.286 [1.54-11.89], p=0.005). CONCLUSION: IL-1ß and IL-1RN polymorphisms associated with H. pylori infection contribute to the development of chronic atrophic gastritis and gastric carcinomas in an Algerian population. The alleles IL-1ß-31C and IL-1RN were associated with an increased risk of developing gastric carcinoma, and IL-1ß-511T with an increased risk of developing chronic atrophic gastritis with no significant association of developing gastric carcinoma.

Immunohistochemical examination of cholecystokinin and gastrin receptors (CCK-2/gastrin-R) expression in normal and exocrine cancerous human pancreatic tissues.

OBJECTIVE: Evaluating tissue samples of normal and exocrine cancerous human pancreas on the expression of CCK2/gastrin receptor. We performed an immunohistochemical protocol that allows efficient detection of this receptor in formalin-fixed, paraffin-embedded human tissues. METHODS: Twenty (20) paraffin blocks of pancreatic tissue sections were collected from the Departments of pathology, Central University Hospital of Sidi-bel-Abbes City (Western Algeria) for the period 2004-2013; ten (10) of them were normal pancreatic samples; and ten (10) cancerous pancreatic sections. The samples were studied using an immunohistochemical protocol for CCK-2/gastrin receptors. RESULTS: Our immunohistochemical analysis revealed that CCK-2/gastrin receptors were expressed in both normal and malignant pancreatic cells but with different immunoreactivity levels and different immunostaining intensity i.e., CCK-2/gastrin receptors were highly expressed within the cytoplasmic area of cancerous cells; 40% of the samples had an immunoreactivity (IR) of (+++) and 60% (++++); the immunostaining was as well very intense since we reported a dark brown staining of the malignant cells. However; in normal pancreatic tissues; CCK-2/gastrin receptors IR levels were very low; 80% of the samples had an IR of (+); and 20% had (++) and the immunostaining was less intense; we noted a light brown staining of few normal pancreatic cells. CONCLUSION: The gastrointestinal peptides CCK could be very interesting targets for exocrine pancreatic cancer therapies; thus further surveys such as western blotting and RTPCR could indentify CCK-2/gastrin receptors as a helpful biomarker for exocrine pancreatic cancer diagnosis and treatment.

Prenatal BoBsTM in the cytogenetic analysis of products of spontaneous miscarriage.

BACKGROUND: Fifty percent of spontaneous miscarriages (SMs) are attributed to chromosomal abnormalities. Cytogenetic analysis is an important tool for patient counselling and assessment of the risk of recurrence in future pregnancies. Conventional karyotyping has been the gold standard for chromosomal investigation of products of conception (POC), but it has limitations due to sample maceration, culture failure and maternal cell contamination. Molecular cytogenetic approaches have therefore been developed and found valuable in the cytogenetic investigation of these samples. The Prenatal BoBsTM and KaryoLite BoBsTM, based on the newly developed BACs-on-BeadsTM technology, have been described as reliable tests for rapid detection of aneuploidies in prenatal and POC samples, respectively. OBJECTIVE: To describe our clinical experience of routine screening of POC samples with Prenatal BoBsTM, the test used by our laboratory in France. METHODS: Seventeen samples collected at the University Hospital of Sidi Bel Abbès (Western Algeria) and a further 60 from the University Hospital of Clermont-Ferrand (France) were analysed (19 chorionic villi from products of curettage, 12 placentas, 9 amniotic cells and 37 biopsy specimens). All were screened for the frequent aneuploidies (chromosomes 13, 18, 21, X and Y) in addition to nine microdeletion/microduplication syndrome regions by Prenatal BoBsTM. Standard karyotyping was performed on 51 samples, but failed in 38 cases. RESULTS: Prenatal BoBsTM identified one trisomy 21 and one deletion of 17p13.3. Furthermore, it provided a conclusive result in cases of culture failure (n=38) and in samples with macerated tissue (n=19). The overall failure rate was 11.4%. CONCLUSIONS: Prenatal BoBsTM is a promising technology that represents a fast, sensitive and robust alternative to routine screening for chromosomal abnormality in products of SM. Furthermore, it overcomes the limitations of conventional karyotyping and current molecular cytogenetic techniques.

Incidence of 17p deletions and TP53 mutation in myelodysplastic syndrome and acute myeloid leukemia with 5q deletion.

TP53 mutations are frequent in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with complex karyotype that include del(5q) and are often associated with deletion of 17p. They have also recently been observed in MDS with isolated del(5q). We assessed the incidence of 17p deletion detected by fluorescence in situ hybridization (FISH) and of TP53 mutations detected by direct sequencing and their correlation and prognostic value in 26 MDS and 17 AML with del(5q). In the 20 cases with isolated del(5q) or one additional abnormality, no 17p deletion was found and 3 of the 18 cases analyzed (17%) had TP53 mutation. In the 23 patients with complex karyotype, 17p deletion was suspected by conventional cytogenetics in 15 cases and confirmed by FISH in 10 of them, while TP53 mutation was found in 8 of the 15 patients tested (53%), only five of whom had 17p deletion. In the whole patient series, TP53 mutations were associated with shorter survival (P = 0.07). We confirm the existence of TP53 mutations in 17% of MDS with isolated del(5q). In patients with del(5q) and complex karyotype, FISH and direct sequencing are complementary techniques to analyze TP53 abnormalities. Our findings also suggest that sequencing of the TP53 gene should be included in the study of patients with del(5q) as a single abnormality or in complex karyotype before lenalidomide treatment.

Alteration of antioxidant defense status precedes humoral immune response abnormalities in macrosomia.

BACKGROUND: This study aimed to investigate whether the anomalies affecting the antioxidant and humoral immune defenses could start at birth and to check whether the decrease in antioxidant defenses may precede the immune abnormalities in macrosomic newborns. MATERIAL/METHODS: Thirty macrosomic and 30 sex-matched control newborns were recruited for a retrospective case-control study at the Maghnia Maternity Hospital of Tlemcen Department (Algeria). RESULTS: The serum IgG levels were similar in both groups. However, plasma ORAC, albumin, vitamin E, SOD, CAT and GSH-Px levels were significantly decreased in macrosomic as compared to control newborns, yet no difference was observed after adjustment for weight. Additionally, serum concentrations of complement C3, MDA and XO were significantly higher in macrosomic as compared to controls before adjustment for weight. Moreover, macrosomia was significantly associated with high levels of complement C3 (OR=8, p=0.002); whereas no association with those of IgG was observed (OR<1, p>0.05). Furthermore, macrosomia was significantly associated with low levels of ORAC (OR=4.96, p=0.027), vitamin E (OR=4.5, p=0.018), SOD (OR=6.88, p=0.020) and CAT (OR=5.67, p=0.017), and with high levels of MDA (OR=10.29, p=0.005). CONCLUSIONS: Abnormalities of the humoral defense system in excessive weight could be preceded by alterations of the anti-oxidative defense and by inflammatory response and activation of innate immunity at birth. Additionally, excessive weight could be a potential factor contributing to decreased anti-oxidative capacity and increased oxidative stress.

Loss, mutation and deregulation of L3MBTL4 in breast cancers.

BACKGROUND: Many alterations are involved in mammary oncogenesis, including amplifications of oncogenes and losses of tumor suppressor genes (TSG). Losses may affect almost all chromosome arms and many TSGs remain to be identified. RESULTS: We studied 307 primary breast tumors and 47 breast cancer cell lines by high resolution array comparative genomic hybridization (aCGH). We identified a region on 18p11.31 lost in about 20% of the tumors and 40% of the cell lines. The minimal common region of loss (Chr18:6,366,938-6,375,929 bp) targeted the L3MBTL4 gene. This gene was also targeted by breakage in one tumor and in two cell lines. We studied the exon sequence of L3MBTL4 in 180 primary tumor samples and 47 cell lines and found six missense and one nonsense heterozygous mutations. Compared with normal breast tissue, L3MBTL4 mRNA expression was downregulated in 73% of the tumors notably in luminal, ERBB2 and normal-like subtypes. Losses of the 18p11 region were associated with low L3MBTL4 expression level. Integrated analysis combining genome and gene expression profiles of the same tumors pointed to 14 other potential 18p TSG candidates. Downregulated expression of ZFP161, PPP4R1 and YES1 was correlated with luminal B molecular subtype. Low ZFP161 gene expression was associated with adverse clinical outcome. CONCLUSION: We have identified L3MBTL4 as a potential TSG of chromosome arm 18p. The gene is targeted by deletion, breakage and mutations and its mRNA is downregulated in breast tumors. Additional 18p TSG candidates might explain the aggressive phenotype associated with the loss of 18p in breast tumors.

Relationship between interleukin-1beta and lipids in type 1 diabetic patients.

BACKGROUND: The auto-immune response leading to type 1 diabetes (T1D) is closely associated with the overproduction of T helper-1 (Th1) cytokines which activate macrophage production of inflammatory mediators such as interleukin (IL)-1beta. The principal aim of this study was to elucidate whether IL-1beta is associated with the development of the inflammatory state of disease and the altered circulating lipid levels in T1D. MATERIAL/METHODS: Sixty-nine T1D and 74 age-matched non-diabetic (ND) subjects were recruited from the outpatient department of Internal Medicine, University Medical Center, Tlemcen, Algeria. RESULTS: The levels of IL-1beta, CRP, HbA1c, CHOL, and LDLc, but not of HDLc, were significantly higher in all T1D subjects than in the ND controls. IL-1beta and CRP were found to be associated with T1D (OR>1). Newly diagnosed T1D subjects exhibited significantly higher IL-1beta, but not CRP, concentrations than controls and long-standing diabetic subjects. TG and HbA1c levels were not statistically different in the two diabetic populations. However, CHOL and LDLc concentrations were significantly higher in long-standing patients than in newly diagnosed ones. HDLc fractions were lower in long-standing patients than in controls and newly diagnosed diabetic subjects. Furthermore, the plasmatic concentrations of IL-1beta, but not of CRP, negatively correlated with CHOL, LDLc, or TG levels and positively with those of CRP in T1D patients. CONCLUSIONS: IL-1beta seems to be associated with the type 1 diabetes inflammatory process. Moreover, a reciprocal relationship exists between newly diagnosed and long-standing T1D patients as far as the levels of this cytokine and circulating lipids are concerned.

HLA DR phenotypic frequencies and genetic risk of Type 1 diabetes in west region of Algeria, Tlemcen.

BACKGROUND: The main genomic region controlling the predisposition to type 1 diabetes is the Human Leukocyte Antigens (HLA) class II of the major histocompatibility complex. Association with different HLA types depends also on the studied populations. In our investigation, we tried to measure the phenotypic HLA class II association frequencies of DR3 and/or DR4 antigens, using a serologic method called microlymphocytotoxicity analysis, in diabetic and nondiabetic (ND) subjects originating from the west-Algerian region of Tlemcen. The aim of the present study was to determine which HLA DR antigens represent a high susceptibility to develop the disease in this area. Using a case-control retrospective study design, we randomly recruited ninety-one related subjects, 39 type 1 diabetics and 52 ND as controls, at the Internal Medicine Board of Medical Centre University of Tlemcen. RESULTS: DR3 antigen frequencies were comparable between the type 1 diabetics and the ND subjects and showed no association with the disease (p = 1.000, OR = 0.95), whereas DR4 and DR3DR4 antigens were associated with susceptibility to develop type 1 diabetes (DR4; OR = 2.10, DR3DR4; OR = 1.30). Also, no incidence for DR3 (p = 0.2646) or DR3DR4 (p = 0.0699) antigen frequencies was related to the sex ratio. However, significant differences in HLA DR4 frequencies between type 1 diabetics and ND were found to be related to sex (p = 0.0085). CONCLUSION: Taken together, our investigation showed that the strongest association with type 1 diabetes was noticed in the presence of HLA DR4 antigens followed by DR3DR4 antigens. This study highlighted a characteristic of Tlemcen population; a history of consanguineous marriages. Association studies between the disease and genetic polymorphisms should be undertaken in a population where consanguinity is more limited to reduce confounding in result interpretations.

[Effect of iron supplementation among pregnant women at mother-and-baby clinic of Sidi Bel Abbès, West Algeria]. / Impact de la supplémentation en fer chez des femmes enceintes suivies au centre de Protection maternelle et infantile de Sidi Bel Abbès (Ouest algérien).

Iron deficiency is the most prevalent nutritional disorder worldwide, especially in developing countries. It occurs when iron absorption does not equal iron requirements plus iron loss. Because iron requirements are especially high in pregnant women, infants, young children, and adolescents, these groups run a high risk of iron-deficiency anemia. In this controlled prospective and longitudinal study of 83 pregnant women, we explored the correlations between various epidemiological characteristics and the onset of anemia. We also looked at the effect of iron supplementation on the hematological parameters among pregnant women with anemia. Blood counts during the first trimester of pregnancy (3 months +/- 2 weeks' gestation) revealed that 31 of the 83 subjects (37.3%) women had anemia (Hb < 11 g/100 ml): 16 moderate (7 g/dl < or = Hb < 10 g/dl) and 15 mild (10 g/dl < or = Hb < 11 g/dl). We detected no cases of severe anemia in our study. Nor did we find a clear correlation between anemia and such factors as age (r = 0.09), number of pregnancies (r = - 0.30), interval between pregnancies (r = 0.03), or number of abortions (r = - 0.18). Nonetheless, iron supplementation of 30 mg/day, prescribed for four months for all the women with anemia (n = 31), improved some of these hematological parameters, increasing hemoglobin and serum iron levels in particular. These two parameters were strongly positively correlated (r = 0.89). We also noted that the red blood cell count (RBC) and the mean corpuscular hemoglobin concentration (MCHC) both increased significantly (p < 0.05) among the anemic women receiving iron supplements. The prevalence of anemia fell from 34.1% in the first trimester, before supplementation, to 6.3% in the third trimester. This finding suggests that the supplementation prevented the fall in hemoglobin and serum iron that occurred among the women without anemia. We think that iron supplementation is a good strategy for treating and preventing anemia during pregnancy.