Nahla Azzam

Prospective study of endoscopic ultrasound performance in suspected choledocholithiasis.

Background:  The close proximity of the echoendoscope to the extrahepatic bile ductal system and its safety make endoscopic ultrasonography (EUS) an excellent method for examining the common bile duct (CBD). The aim of the present study was to compare EUS diagnostic performance for CBD stones with endoscopic retrograde cholangiography (ERC).

Associations between Single Nucleotide Polymorphisms of COX-2 and MMP-2 Genes and Colorectal Cancer Susceptibility in the Saudi Population

BACKGROUND It has been reported that COX-2 expression is associated with MMP-2 expression in thyroid and breast cancers, suggesting that MMPs are linked to COX-2-mediated carcinogenesis. Several polymorphisms within the MMP2 promoter region have been reported in cases with oncogenesis and tumor progression, especially in colorectal carcinogenesis. MATERIALS AND METHODS This research evaluated risk of association of the SNPs, including genes for COX-2 (A/G transition at +202) and MMP-2 (C/T transition at-1306), with colorectal cancer in 125 patients and 125 healthy controls. RESULTS AND CONCLUSIONS Our data confirmed that MMP2 C-1306 T mutations were significantly more common in colon cancer patients than in our control Saudi population; p=0.0121. On the other hand in our study, there was no significant association between genotype distribution of the COX2 polymorphism and colorectal cancer; p=0.847. An elevated frequency of the mutated genotype in the control group as compared to the patients subjects indeed suggested that this polymorphism could decrease risk in the Saudi population. Our study confirmed that the polymorphisms that could affect the expressions of MMP-2 and COX-2 the colon cancer patients were significantly higher than that in the COX-2 negative group. The frequency of individuals with MMP2 polymorphisms in colon cancer patients was higher than individuals with combination of COX2 and MMP2 polymorphisms. Our study confirmed that individuals who carried the polymorphisms that could affect the expressions of COX2 are more susceptible to colon cancer. MMP2 regulatory polymorphisms could be considered as protective; further studies need to confirm the results with more samples and healthy subjects.

Prevalence and clinical features of colonic diverticulosis in a Middle Eastern population

AIM To determine the prevalence, location, associations and clinical features of colonic-diverticulosis and its role as a cause of lower-gastroenterology-bleeding. METHODS We retrospectively reviewed the medical records of 3649 consecutive patients who underwent a colonoscopy for all indications between 2007 and 2011 at King Khalid University Hospital, Riyadh, Saudi Arabia. The demographic data were collected retrospectively through the hospitals information system, electronic file system, endoscopic e-reports, and manual review of the files by two research assistants. The demographic information included the age, sex, comorbidities and indication for the colonoscopy. The association among colonic polyps, comorbidities and diverticular disease was also measured. RESULTS A total of 270 patients out of 3649 were diagnosed with colonic diverticulosis, with a prevalence of 7.4%. The mean age was 60.82 years ± 0.833, (range 12-110). Females comprised 38.89% (95%CI: 33-44.7) of the study population. The major symptoms were rectal bleeding in 33.6%, abdominal pain in 19.3%, constipation in 12.8% and anemia in 6%. Diverticula were predominantly left-sided (sigmoid and descending colon) in 62%, right-sided in 13% and in multiple locations in 25%. There was an association between the presence of diverticulosis and adenomatous polyps (P-value < 0.001), hypertension (P-value < 0.0001) and diabetes mellitus (P-value < 0.0016). Diverticular disease was the second most common cause of lower gastrointestinal bleeding, in 33.6% (95%CI: 27.7-39.4), after internal hemorrhoids, in 44.6% (95%CI: 40.3-48.9). On multivariable logistic regression, hypertension (OR = 2.30; 95%CI: 1.29-4.10), rectal bleeding (OR = 2.57; 95%CI: 1.50-4.38), and per year increment in age (OR = 1.05; 95%CI: 1.03-1.07) were associated with diverticulosis but not with bleeding diverticular disease. LIMITATIONS A small proportion of the patients included had colonoscopies performed as a screening test. CONCLUSION Colonic-diverticulosis was found to have a low prevalence, be predominantly left-sided and associated with adenomatous-polyps. Age, hypertension and rectal bleeding predict the presence of diverticular disease.

Matrix Metalloproteinase-2 (-1306 C>T) Promoter Polymorphism and Risk of Colorectal Cancer in the Saudi Population

BACKGROUND Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism (SNP) at -1306, which disrupts a Sp1-type promoter site (CCACC box), results in strikingly lower promoter activity with the T allele. In the present study, we investigated whether this MMP-2 genetic polymorphism might be associated with susceptibility to colorectal cancer (CRC) in the Saudi population. We also analyzed MMP-2 gene expression level sin CRC patients and 4 different cancer cell lines. MATERIALS AND METHODS TaqMan allele discrimination assays and DNA sequencing techniques were used to investigate the C-1306T SNP in the MMP-2 gene of Saudi colorectal cancer patients and controls. The MMP-2 gene expression level was also determined in 12 colon cancer tissue samples collected from unrelated patients and histologically normal tissues distant from tumor margins. RESULTS AND CONCLUSIONS The MMP-2 C-1306T SNP in the promoter region was associated with CRC in our Saudi population and the MMP-2 gene expression level was found to be 10 times higher in CRC patients. The MMP-2 C-1306T SNP is significantly associated with CRC in the Saudi population and this finding suggested that MMP-2 variants might help predict CRC progression risk among Saudis. We propose that analysis of this gene polymorphism could assist in identification of patient subgroups at risk of a poor disease outcome.

Cytochrome P450 1A1, 2E1 and GSTM1 Gene Polymorphisms and Susceptibility to Colorectal Cancer in the Saudi Population

BACKGROUND The Saudi population has experienced a sharp increase in colorectal and gastric cancer incidences within the last few years. The relationship between gene polymorphisms of xenobiotic metabolizing enzymes and colorectal cancer (CRC) incidence has not previously investigated among the Saudi population. The aim of the present study was to investigate contributions of CYP1A1, CYP2E1, and GSTM1 gene polymorphisms. MATERIALS AND METHODS Blood samples were collected from CRC patients and healthy controls and genotypes were determined by polymerase chain reaction restriction fragment length polymorphism and sequencing. RESULTS AND CONCLUSIONS CYP2E1*6 was not significantly associated with CRC development (odd ratio=1.29; confidence interval 0.68-2.45). A remarkable and statistically significant association was observed among patients with CYP1Awt/*2A (odd ratio=3.65; 95% confidence interval 1.39-9.57). The GSTM1*0/*0 genotype was found in 2% of CRC patients under investigation. The levels of CYP1A1, CYP2E1 and GSTM1 mRNA gene expression were found to be 4, 4.2 and 4.8 fold, respectively, by quantitative real time PCR. The results of the present case-control study show that the studied Saudi population resembles Caucasians with respect to the considered polymorphisms. Investigation of genetic risk factors and susceptibility gene polymorphisms in our Saudi population should be helpful for better understanding of CRC etiology.

CARD15/NOD2, CD14 and Toll-like 4 Receptor Gene Polymorphisms in Saudi Patients with Crohn's Disease

Crohn’s disease (CD) is a multifactorial disease with a genetic component and an observed association with genes related to the innate immune response. Polymorphisms in the CARD15/NOD2 gene, in addition to functional variants of the toll-like receptor-4 (TLR4) and CD14 genes, have been associated with the development of Crohn’s disease. There is no information about the frequency of these polymorphisms in the Saudi population. We examined the frequency of the three major CARD15/NOD2 risk alleles (Leu1007fsinsC, Arg702Trp, and Gly908Arg) and the TLR4 (Thr399Il) polymorphism as well as a functional polymorphism in the promoter of the CD14–159C/T in 46 Saudi CD patients and 50 matched controls. Genotyping was performed by allele-specific PCR or by restriction fragment length polymorphism (PCR-RFLP) analysis. The mutant genotype frequencies of the Leu1007fsinsC, Arg702Trp and Gly908Arg in the patient group were 6.5, 21.7 and 6.5%, respectively, compared with frequencies of 0, 4 and 2%, respectively, in the control group. There were 15 patients who carried the mutant alleles for all three CARD15/NOD2 variants, Leu1007fsinsC, Arg702Trp and Gly908Arg, while none of the control candidates carried the three alleles. This genetic study provides evidence that the three major CARD15/NOD2 variant alleles and the CD14 –159C/T polymorphism are associated with Crohn’s disease (CD) susceptibility in the Saudi population; however, there is no evidence that the TLR4 (Thr399Il) or CARD15/NOD2 polymorphisms can be considered risk factors for Crohn’s disease.

Efficacy of spyglass-guided electrohydraulic lithotripsy in difficult bile duct stones.

Background/Aims: We aimed to evaluate the efficacy and safety of Spyglass-guided electrohydraulic lithotripsy (EHL) for difficult common bile duct stones (CBD) not amenable to conventional endoscopic therapy. Design: A retrospective study evaluating the efficacy of Spyglass-guided EHL in treating difficult CBD stones, in a single tertiary care center. Patients and Methods: All patients who underwent Spyglass-guided EHL from 2012 to 2013 were compared with a historical cohort who had ECSWL. Results: A total number of 13 patients underwent Spyglass-guided EHL, 8 (61.5%) of them were males. The mean age was 46.5 ± 5.6 years. Bile duct clearance was achieved in 13 (100%) of them. Seventy-six percent required only one Endoscopic Retrograde Cholangiopancreatography (ERCP) to clear the CBD, 7.7% required two ERCPs, and 15.4% required three ERCPs. Adverse effects (cholangitis) occurred in one patient (10%), whereas only 30 patients (64.4%) of the ESWL group had complete CBD stone clearance. Thirty-seven percent required one ERCP to clear the CBD, 35.6% required two ERCPs, and 20% required three ERCPs. Adverse effects happened in seven (15.5%) patients, where five (11%) had cholangitis and two (4.4%) had pancreatitis. Conclusion: Although a retrospective design with a small sample size, we concluded that Spyglass-guided EHL is an effective procedure in treating difficult CBD stones.

Natural anticoagulants can be useful predictors of severity in chronic liver disease.

Protein S (PS), protein C (PC), and antithrombin (AT) are produced by the liver, and their levels were previously shown to be reduced in chronic as well as acute liver disease. The aim of this study was to determine whether measurement of PS, PC, and AT levels in patients would be as good as the commonly used clinical and histological parameters of liver disease in discriminating early and advanced hepatocyte dysfunction. A total of 154 patients were recruited and categorized into five groups: hepatitis B inactive carriers in group 1 (n = 29), nonalcoholic steatohepatitis patients in group 2 (n = 30), chronic hepatitis B patients with elevated liver enzymes in group 3 (n = 29), chronic hepatitis C patients with elevated liver enzymes in group 4 (n = 30), liver cirrhosis patients in group 5 (n = 36). There were significant differences between groups in the levels of PC (P = 0.0001), total PS (P = 0.0001), and free PS (P = 0.0001) and AT (P = 0.0001). These parameters were least affected in the control group, then groups 1 and 2, followed by groups 3 and 4, and most affected in group 5. No differences in these tests were detected between groups 1 and 2 and between groups 3 and 4. Univariate and multivariate analyses showed that free PS was the only predictor of significant inflammation (P = 0.0001), and AT (P = 0.001) and PC (P = 0.003) were the most important factors associated with advanced fibrosis. Both PS and PC are sensitive markers of liver disease, but PS is a sensitive marker of liver inflammation, whereas PC may be a more sensitive marker for liver fibrosis.

Prevalence and characteristics of colonic polyps and adenomas in 2654 colonoscopies in Saudi Arabia.

Background/Aims: Colorectal cancer (CRC) is the second most common malignancy in the Saudi population, with an increasing incidence over the past 20 years. We aim to determine the baseline polyp as well as adenoma prevalence in a large cohort of patients and to find the possible age in which, if deemed appropriate, a CRC screening program should be initiated. Patients and Methods: A retrospective cohort study was conducted using an endoscopic reporting database of individuals seen at a major tertiary care university hospital (King Khalid University Hospital) in Riyadh, Saudi Arabia. Consecutive Saudi patients who underwent a colonoscopy between August 2007 and April 2012 were included. Patients were excluded if the indication for the colonoscopy was colon cancer, colonic resection, active colitis, active diverticulitis, inflammatory bowel disease, or if the patient was referred for polypectomy. Results: 2654 colonoscopies were included in the study. The mean age of the study population was 50.5 years [standard deviation (SD) 15.9] and females represented 57.7%. The polyp detection rate in completed colonoscopies was 20.8% (95% CI: 19.2-22.5). Adenomas were found in 8.1% (95% CI: 7.1-9.1), while advanced adenomas were found in only 0.5% (95% CI: 0.2-0.7). Adenomas were found in the left side of the colon in 33.9%, followed by the rectum in 14.6%, ascending colon and cecum in 14.2%, transverse colon in 8.7%, and in multiple locations in 28.7%. Those with a prior history of polyps or CRC were more likely to have an adenoma at colonoscopy than those who did not (14.3% vs. 6.6%; P < 0.01). The adenoma prevalence varied between age groups and ranged from 6.2% to 13.6% with a higher proportion in older individuals; this trend was seen both in males (6.0-14.5%) and females (6.4-14.6%) as well as in those who had screening colonoscopies (6.3-18.4%). No age could be found at which a CRC screening program would be appropriate to initiate. Conclusion: The prevalence of polyps and adenomas in this cohort is less than that reported in the Western populations. But as this cohort included younger and symptomatic patients with only a small proportion undergoing screening, further studies in an asymptomatic population are needed.

Complications and survival in patients undergoing colonic stenting for malignant obstruction

AIM To investigate whether predicting patients that might be at a higher risk for complications might serve to improve the selection of patients undergoing colonic stenting. METHODS A retrospective review of consecutive patients who underwent an attempted self-expandable metal stent (SEMS) insertion for malignant colonic obstruction between November 2006 and March 2013. All patients were either referred for preoperative colonic decompression with the intent of a single surgical procedure, or for palliation of the malignant colorectal obstruction for unresectable cancer. Fishers test or χ(2) test was performed on categorical variables, and the t test for continuous variables. Univariable and multivariable logistic regression were used to examine the association between independent variables and the presence of complications from SEMS insertion. RESULTS SEMS insertion was attempted in 73 patients. Males comprised 55.71% and the mean age was 67.41 ± 12.41 years. Of these, 65.15% underwent subsequent surgery, while 34.85% received SEMS as palliation for advanced disease. Extracolonic tumors were only 4.76%. The majority of patients had stage IV disease (63.83%), while the remainder had stage III (36.17%). SEMS were successfully inserted in 93.85% (95%CI: 87.85%-99.85%). Perforations occurred in 4.10%, SEMS migration in 8.21%, and stent re-occlusion from ingrowth occurred in 2.74% of patients. The mean duration of follow up for the patients was 13.52 ± 17.48 mo (range 0-73 mo). None of the variables: age, sex, time between the onset of symptoms to SEMS insertion, time between SEMS insertion and surgery, length of the stenosis, location of the stenosis, albumin level, or receiving neoadjuvant chemotherapy, could predict the development of complications from either SEMS insertion nor prolonged survival. CONCLUSION None of the variables could predict the development of complications or survival. Further studies are required to identify patients who would benefit the most from SEMS.