Othman Alharbi

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.

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.

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.

Expression and Polymorphism of Toll-Like Receptor 4 and Effect on NF-κB Mediated Inflammation in Colon Cancer Patients.

Our aim was to evaluate the association between the expression and the polymorphism of TLR4/NF-κB pathways and colon cancer. TLR4 (rs4986790, rs10759932, rs10759931 and rs2770150) were genotyped in blood samples from Colorectal patients and healthy controls. TLR4 and cytokines inflammatory expression were evaluated by real time PCR on 40 matching normal and colon tissues and the protein level by Immunohistochemistry. The high level of TLR4 expression in colon cancer tissues is mainly due to infections by bacteria in the human colon and leads to induction of an acute secretion of inflammatory cytokines mediated by NF-κB. Also, we report here a clear evidence for an association between TLR4 rs10759931 polymorphism (OR = 0.086, CI: 0.04–0.18, P = <0.00001). This polymorphism affects the entire population without being specific to either gender or to any age group. In contrast, the rs2770150 is associated with colon cancer in women aged over 50 years and is closely linked with the decreased levels of female sex hormones during the post-menopausal period (OR = 0.188, CI: 0.074–0.48, P = <0.00084). rs10759932 and rs4986790 appear to have any association with colon cancer. Our data suggest that TLR4 SNPs could possibly serve as biomarkers for decision making in colon cancer treatment.

Prevalence of symptoms of gastroesopahgeal reflux in a cohort of Saudi Arabians: a study of 1265 subjects.

Background/Aims: In this study, we aimed to determine the prevalence of gastroesophageal reflux disease (GERD) in the general population of the capital city of Riyadh and to assess its association with other factors including age, smoking, body mass index (BMI), asthma, as well as the presence of other co-morbid diseases. Materials and Methods: We used the Gastroesophageal Reflux Disease Questionnaire (GerdQ) for diagnosing GERD, based on a GerdQ score of 8 or more. Riyadh was divided into four quadrants, and from each area, a single shopping mall was chosen randomly to conduct our surveys. Data collected included age, sex, history of smoking, history of asthma or any other medical condition, dietary habits, monthly household income, history and frequency of heartburn, epigastric pain, regurgitation of food, nausea, sleep disturbance from heartburn, the use of common over-the-counter antacids for the control of their symptoms, and their height and weight. Results: Over a 4-week period from the 19 December 2012 to 17 January 2013, a total of 1265 individuals were included in the survey. The mean age was 29.97 ± 11.58 years. Females formed 67.81% of the respondents and 62.73% had one or more episodes of heartburn per week. Based on a cutoff GERDQ score of 8, the prevalence of GERD in the surveyed population was 45.4%. GERD was more prevalent in older individuals (mean age 31.9 vs. 30.0 years, P < 0.001) and in those with a higher BMI (27.29 vs. 26.31 kg/m2, P = 0.02). There was no difference between males (45.43%) and females (45.13%) (P = 0.92); there was a trend of a higher prevalence in smokers (51.63% vs. 44.41%), but it did not reach statistical significance (P = 0.09). Conclusion: Symptoms suggestive of GERD as determined by the translated GerdQ are prevalent among this study population.

Clinical epidemiology of ulcerative colitis in Arabs based on the Montréal classification

AIM To determine the clinical, epidemiological and phenotypic characteristics of ulcerative colitis (UC) in Saudi Arabia by studying the largest cohort of Arab UC patients. METHODS Data from UC patients attending gastroenterology clinics in four tertiary care centers in three cities between September 2009 and September 2013 were entered into a validated web-based registry, inflammatory bowel disease information system (IBDIS). The IBDIS database covers numerous aspects of inflammatory bowel disease. Patient characteristics, disease phenotype and behavior, age at diagnosis, course of the disease, and extraintestinal manifestations were recorded. RESULTS Among 394 UC patients, males comprised 51.0% and females 49.0%. According to the Montréal classification of age, the major chunk of our patients belonged to the A2 category for age of diagnosis at 17-40 years (68.4%), while 24.2% belonged to the A3 category for age of diagnosis at > 40 years. According to the same classification, a majority of patients had extensive UC (42.7%), 35.3% had left-sided colitis and 29.2% had only proctitis. Moreover, 51.3% were in remission, 16.6% had mild UC, 23.4% had moderate UC and 8.6% had severe UC. Frequent relapse occurred in 17.4% patients, infrequent relapse in 77% and 4.8% had chronic disease. A majority (85.2%) of patients was steroid responsive. With regard to extraintestinal manifestations, arthritis was present in 16.4%, osteopenia in 31.4%, osteoporosis in 17.1% and cutaneous involvement in 7.0%. CONCLUSION The majority of UC cases were young people (17-40 years), with a male preponderance. While the disease course was found to be similar to that reported in Western countries, more similarities were found with Asian countries with regards to the extent of the disease and response to steroid therapy.

Association between TLR-9 polymorphisms and colon cancer susceptibility in Saudi Arabian female patients

Objective The authors aimed to explore the relationship between the expression/polymorphisms of TLR-9 and susceptibility to colon cancer development in the Saudi Arabian population. Methods In total, blood samples from 115 patients with colon cancer and 102 participants without colon cancer were analyzed in this study. Three single-nucleotide polymorphisms (SNPs) were selected from the TLR-9 gene, including two sites within the TLR-9 gene’s promoter region (rs352144 and rs187084) and one site in a TLR-9 intron region (rs5743839). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models after adjusting for age, gender, and tumor localization. To investigate the differential expression of TLR-9 in colon cancer, TLR-9 expression was evaluated using quantitative real-time reverse transcription polymerase chain reaction on 40 matched normal and colon tissues. Results The authors found that TLR-9 expression was decreased in colon cancer tissues as compared with that in normal tissues. Moreover, significant associations between the TLR-9 rs187084 SNP and colon cancer risk were observed in female patients only. In rs187084, the T allele had a significantly lower frequency (2.8 times) in female cancer patients than in controls (0.27 vs 0.41). The TLR-9 rs352139 and rs352144 SNPs were significantly associated with colon cancer development when the tumor was located in the rectal area. Conclusion The findings support the hypothesis that TLR-9 has an anticancer role in colon cancer development. Furthermore, genetic variation may influence colon cancer development, and SNPs in TLR-9 could serve as biomarkers for decision making in the treatment of females with rectal cancer.