Colorectal cancer is a major health concern as it ranks third in incidence and second major cause of cancer-related deaths worldwide. A leading cause of treatment failure has been attributed to cancer stem cells that can invariably resist existing chemotherapeutic regimens. Notch signaling pathway has been involved in the maintenance of stem cells besides being crucial in cell fate decision and embryonic development. This pathway has also been implicated in several human malignancies including colorectal cancer. We investigated mRNA expression of four Notch receptors (Notch1–4), five ligands (Jag1, Jag2, Dll1, Dll3, and Dll4), and four target genes (Hes1, Hes5, Hey1, and Hey2) using highly specific TaqMan gene expression assays in colorectal adenomas and cancers. Upregulated expression of Notch receptors ranged between 29 and 73% in colorectal cancers and between 11 and 56% in adenomas. Expression of Notch3 and Notch4 receptors was significantly higher in colorectal cancers compared to normal and adenoma tissues. The Jagged and Delta-like ligands were overexpressed between 25 and 52% in colorectal cancers, while in adenomas, it ranged between 0 and 33%. Combining the data for upregulation of receptors and ligands suggests that 86% colorectal cancers and 56% adenomas exhibited overexpression of Notch pathway genes in our cohort. Notch target genes were upregulated between 24 and 33% in colorectal cancers and between 11 and 22% in adenomas. Collating upregulation of Notch receptors and ligands with the target genes showed concordance in 58% colorectal tumors. Additionally, we evaluated expression of Notch receptors, ligands, and target genes with prognosis using the TCGA mRNA expression dataset. Patients overexpressing Notch3, Notch4, and Hey1 had significantly poorer overall survival relative to those having lower levels of these genes. Taken together, Notch signaling components are aberrantly overexpressed in colorectal tumors, and development of therapeutics targeting the Notch pathway may prove to be beneficial in the management of colorectal cancers.

Background/Aims: The aim of this study is to predict cases where the clearance of the biliary system from stones at the initial endoscopic retrograde cholangiopancreatography (ERCP) might be of value for better risk-stratifying patients. We attempted to identify factors that are associated with a higher failure rate of clearing the biliary system on the index ERCP. Patients and Methods: This is a retrospective study from January 2008 to January 2015. All patients with bile duct stones confirmed on ERCP were included in this study. Patients who had prior attempts of bile duct stone extraction were excluded. Results: A total of 554 ERCPs were performed to extract biliary duct stones from 426 patients. The mean age was 46.3 years and 41.7% were males. The group where the index ERCP did not clear the biliary system tended to be older (50.4 vs. 45.2 years, P = 0.03). On multivariate analysis, the presence of fever (OR 4.64; 95% CI, 1.66–12.79), a larger number of filling defects (OR 1.34; 95% CI, 1.13–1.93), presence of a stricture distal to a stone (OR 4.63; 95% CI, 1.36–15.78), the use of an extraction basket (OR 3.23; 95% CI, 1.56–6.74), and/or mechanical lithotripsy (OR 3.05; 95% CI, 1.10–8.49) were all associated with a lower odds of clearing the biliary system. The use of an extraction balloon was associated with the success of clearing the biliary system (99.7% vs. 77.4%, P < 0.01) and a lower odds of failing (OR 0.01; 95% CI, 0.00–0.08) on multivariate analysis. Conclusion: A few of the characteristics that are found on cholangiography at the index ERCP could be used to identify patients that might require more than one ERCP to clear the biliary system from stones.

Background: There has been an increase in incidence and prevalence of inflammatory bowel disease (IBD) outside the western countries. Treatment costs are an essential component for healthcare planning and priority setting. The utilization patterns and annual administration and cost of IBD medications are largely unknown in countries with an increasing incidence of disease, Saudi Arabia being an example. Aim: To evaluate the use of non-biologic and biologic agents and their associated annual administration costs in a sample of patients with Crohn’s disease (CD) and ulcerative colitis (UC) in Saudi Arabia. Methods: Single-center retrospective chart review was performed to determine the use of biologic and non-biologic medications among IBD patients in a tertiary care hospital in Riyadh, Saudi Arabia. Daily and the annual acquisition cost of different IBD therapeutic agents was calculated. The utilization rates and cost of each type of medication by CD and UC patients were compared. Results: Data of 258 CD patients and 249 UC patients were analyzed. Infliximab and adalimumab were the most commonly prescribed biologics among the study sample, however, their utilization rates were significantly higher among CD than UC patients (36.82% vs. 11.24%, and 20.54% vs. 9.64%, respectively, P < 0. 01). Azathioprine utilization rate was also higher among CD patients compared to their UC counterparts (71.71% vs. 40.16%, respectively, P < 0.01). However, the utilization rate of mesalazine in the UC patients was significantly higher than their CD counterparts (85.53% vs. 14.34% for CD, P < 0.01). The annual cost of biologics (including administration and lab test cost) ranged from 5572 USD for ustekinumab to 18,424 USD for vedolizumab. On the other hand, the annual cost of non-biologics ranged from 16 USD for prednisone to 527 USD for methotrexate. Conclusion: Biologics are extensively used in the management of IBD, particularly CD, and their utilization costs are significantly higher than non-biologics. Future studies should examine the cost effectiveness of IBD medications especially in countries with increasing incidence such as Saudi Arabia.

This study’s objectives were to examine and compare the cost-effectiveness of biologic and non-biologic therapies in the improvement of the health-related quality of life (HRQoL) of patients with i...

Background: Colorectal cancer is the third most common malignancy in Saudi Arabia. The best therapeutic regimen for colorectal cancer is a matter of ongoing debate and data on its treatment in Saudi Arabia are limited. Purpose: The objective of this study was to explore the predictors of survival and to compare the risk of mortality among colorectal cancer patients treated with different therapeutic modalities. Patients and Methods: The study utilized data from the electronic colorectal cancer registry of a university-affiliated tertiary care hospital. The Kaplan-Meier survival analysis was used to estimate the survival rates over 36 months of follow-up across rectal and colon cancer patients as well as different sociodemographic and medical characteristics. Bivariate and multiple Cox proportional-hazards regressions were conducted to estimate the risk of mortality among rectal and colon cancer patients undergoing different treatments. Results: The number of patients in the registry who were followed up for 36 months was 143 patients. The majority of patients had colon cancer (74.13%). Rectal cancer patients had generally better survival estimates compared to their colon cancer counterparts. Colon cancer patients treated with chemotherapy had a significantly lower risk of mortality controlling for the use of surgery, radiotherapy, and other variables including age, gender, stage of cancer, and family history of colorectal cancer (HR=0.33; P=0.03). Additionally, colon cancer patients with a family history of colorectal cancer had significantly higher risk of mortality (HR=3.40; P=0.02). Conclusion: The findings of this study highlight the value of chemotherapy in managing colon cancer patients.