Gastroenterology

The missing "C": Crohn's, colitis and coping Turki AlAmeel, Mahmoud Mosli Saudi Journal of Gastroenterology 2019 25(3):143-144

The regulatory roles of long noncoding RNAs in the biological behavior of pancreatic cancer Ying Li, Xiaojuan Yang, Xiaoning Kang, Shanglong Liu Saudi Journal of Gastroenterology 2019 25(3):145-151 Long noncoding RNAs (lncRNAs) are a new class of regulators. LncRNAs are defined as endogenous transcribed RNA molecules with transcript length of >200 nt. Accumulating evidence has shown that lncRNAs are involved in many physiological processes such as cell cycle regulation, cell apoptosis and survival, cancer migration and metabolism. However, the biological and molecular mechanisms of lncRNAs in pancreatic cancer are still unclear. Recent studies have reported that many lncRNAs are dysregulated in pancreatic cancer and closely associated with tumorigenesis, diagnosis and prognosis. In this review, we described the regulation and functional role of lncRNAs and the potential underlying mechanism involved in pancreatic cancer, outlined the roles of lncRNA in pancreatic cancer, and discussed the potential possibility of lncRNAs as therapeutic targets in clinical practice. Moreover, the potential of lncRNAs used as sensitive biomarkers for diagnosis, prognosis and prediction of response to therapy in pancreatic cancer will also be discussed.

The role of imaging in determining prognosis for primary sclerosing cholangitis: A systematic review Dan Segal, Paul Marotta, Mahmoud Mosli, Guangyong Zou, Brian G Feagan, Bandar Al-Judaibi Saudi Journal of Gastroenterology 2019 25(3):152-158 Background/Aims: Primary sclerosing cholangitis (PSC) is a chronic, progressive, fibrotic bile duct disease. Resultant complications include infection, progressive liver disease and cancer. While diagnosis relies extensively on imaging, the role of imaging in determining prognosis is unclear. The aim of this study was to systematically review existing imaging indices and features that predict PSC progression. Materials and Methods: We performed a systematic review of imaging features that predict PSC progression. PubMed, EMBASE, MEDLINE, Clinicaltrials.gov and the Cochrane Library were searched from inception to November 2018 for relevant studies. Pertinent data were extracted and assessed. Study quality was evaluated using the Newcastle-Ottawa scale (NOS). Results: The search returned 2504 results. Nine studies were included in the final review. Four studies evaluated the prognostic value of imaging features and five evaluated prognostic algorithms. The mean NOS score was 4.44 ± 0.98 on a scale of 0 to 9. Imaging features that were of prognostic value were degree of intrahepatic duct narrowing, the presence of a dominant biliary duct stricture and percentage of narrowed intraheptic ducts. Three imaging indices (one endoscopic retrograde cholangiopancreatography (ERCP)-based and two magnetic resonance-based) had been derived. The ERCP index was validated in a second cohort and subsequently updated to improve its predictive ability. The magnetic resonance cholangiopancreatography (MRCP) index was validated in two studies and was found to be predicative of transplant-free survival. A modified MRCP index (MRCP-risk score) was evaluated in a prospective multicenter study and was found to be predicative of PSC-related disease progression. Conclusion: In conclusion, ERCP and MRCP-based indices have short-term prognostic value in PSC. However, more studies are required to validate their predictability of disease-related progression, such as liver decompensation, ascending cholangitis, cholangiocarcinoma and liver transplantation.

Maladaptive coping, low self-efficacy and disease activity are associated with poorer patient-reported outcomes in inflammatory bowel disease Che-Yung Chao, Carolyne Lemieux, Sophie Restellini, Waqqas Afif, Alain Bitton, Peter L Lakatos, Gary Wild, Talat Bessissow Saudi Journal of Gastroenterology 2019 25(3):159-166 Background/Aims: Patient-reported outcomes (PRO) are key aspects in the management of inflammatory bowel disease (IBD). This study aims to evaluate factors associated with adverse PRO, including modifiable social constructs of maladaptive coping and self-efficacy as well as physician–patient concordance on PRO. Patients and Methods: This cross-sectional study was performed in patients with Crohn's disease (CD) or ulcerative colitis (UC) from September 2015 to March 2016. Validated questionnaires were used to assess quality of life (Short IBD Questionnaire), disability (IBD disability index), productivity (work productivity and activity impairment questionnaire), anxiety/depression (Hospital Anxiety and Depression Scale), coping strategies [Brief Coping Operations Preference Enquiry (Brief COPE)], and self-efficacy (General Self-Efficacy Scale). Independent physician assessment was used to compare concordance with patients. Results: In all, 207 (CD: 144 and UC: 63) patients, with median age of 39 years, were included, with 42.5% males. Significant proportion of patients reported moderate/severe impairment of disability (30.5%), quality of life (29.4%), productivity (52.4%), anxiety (32.9%) and depression (23.3%). Disease activity and maladaptive coping were independently associated with unfavourable PRO, whereas self-efficacy had a positive effect in multivariate analysis. Physicians could accurately identify the magnitude of PRO impairment in standard clinical settings (r = 0.59–0.65, P < 0.001). Conclusion: Disease activity and modifiable psychological constructs are associated with unfavorable PRO in patients with IBD. These factors could assist with identifying high-risk patients, many of whom may benefit from targeted interventions to improve health outcomes.

Cytochrome P450 family members are associated with fast-growing hepatocellular carcinoma and patient survival: An integrated analysis of gene expression profiles Zhao-Zhen Liu, Li-Na Yan, Chun-Nan Dong, Ning Ma, Mei-Na Yuan, Jin Zhou, Ping Gao Saudi Journal of Gastroenterology 2019 25(3):167-175 Background/Aims: The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. Although many molecular tools have been developed to assist in stratification and prediction of patients by using microarray analysis, the classification and prediction are still improvable because the high-through microarray contains a large amount of information. Meanwhile, gene expression patterns and their prognostic value for HCC have not been systematically investigated. In order to explore new molecular diagnostic and prognostic biomarkers, the gene expression profiles between HCCs and adjacent nontumor tissues were systematically analyzed in the present study. Materials and Methods: In this study, gene expression profiles were obtained by repurposing five Gene Expression Omnibus databases. Differentially expressed genes were identified by using robust rank aggregation method. Three datasets (GSE14520, GSE36376, and GSE54236) were used to validate the associations between cytochrome P450 (CYP) family genes and HCC. GSE14520 was used as the training set. GSE36376 and GSE54236 were considered as the testing sets. Results: From the training set, a four-CYP gene signature was constructed to discriminate between HCC and nontumor tissues with an area under curve (AUC) of 0.991. Accuracy of this four-gene signature was validated in two testing sets (AUCs for them were 0.973 and 0.852, respectively). Moreover, this gene signature had a good performance to make a distinction between fast-growing HCC and slow-growing HCC (AUC = 0.898), especially for its high sensitivity of 95%. At last, CYP2C8 was identified as an independent risk factor of recurrence-free survival (hazard ratio [HR] =0.865, 95% confidence interval [CI], 0.754–0.992, P = 0.038) and overall survival (HR = 0.849; 95% CI, 0.716–0.995, P = 0.033). Conclusions: In summary, our results confirmed for the first time that a four-CYP gene (CYP1A2, CYP2E1, CYP2A7, and PTGIS) signature is associated with fast-growing HCC, and CYP2C8 is associated with patient survival. Our findings could help to identify HCC patients at high risk of rapid growth and recurrence.

Outcome of biliary atresia among Saudi children: A tertiary care center experience Sinan Holdar, Badr Alsaleem, Ali Asery, Abdulrahman Al-Hussaini Saudi Journal of Gastroenterology 2019 25(3):176-180 Background/Aims: Data from Western countries indicate that biliary atresia (BA) is the leading cause of end-stage liver disease in children and the most common indication for liver transplantation (LT) in the pediatric population. There is no data on the epidemiology and outcome of BA in Saudi Arabia. The main objective of our study was to understand the clinical and epidemiological characteristics and outcome of BA in the Saudi population. Patients and Methods: We retrospectively reviewed the database of infantile cholestasis cases that presented to our center from 2008 to 2015 and identified BA cases. Data on clinical, biochemical, imaging, and histopathological characteristics were collected by chart review. The two primary study outcomes were (1) successful Kasai portoenterostomy (KPE) defined as resolution of jaundice (total serum bilirubin <20 μmol/L) and (2) survival with native liver. Results: Over the study period, we evaluated 450 cases of infantile cholestasis. In all, 21 cases (11 males) were diagnosed with BA (4.7%). BA cases were first seen by pediatric gastroenterologists at a median age of 65 days. KPE was performed in 12 cases at a median age of 73 days. Successful KPE was achieved in four cases (33%). Five of the remaining eight cases had LT and three died before LT. Nine of the 21 BA cases were denied KPE and had primary LT at median 8 months of age. The native liver 4-year survival rate was 14.3% and the overall survival rate was 81%. Conclusion: BA is an uncommon cause of infantile cholestasis in Saudi Arabia. Our study provides a snapshot of the epidemiology of BA in Saudi Arabia that is characterized by late referral to pediatric gastroenterologists and poor outcome without LT.

Helicobacter pylori DNA promotes cellular proliferation, migration, and invasion of gastric cancer by activating toll-like receptor 9 Xiang-Rong Qin, Jia Wu, Xin-Yu Yao, Jin Huang, Xiao-Yong Wang Saudi Journal of Gastroenterology 2019 25(3):181-187 Background/Aim: Helicobacter pylori (H. pylori) infection is a well-known risk factor for gastric cancer. Toll-like receptor 9 (TLR9) plays an important role in many cancers and is important for immunity to H. pylori infection. Thus, the present study aimed to evaluate the influence of H. pylori on TLR9 and explore its roles in gastric cancer. Materials and Methods: TLR9 expression in MKN45 cells, which were cocultured with or without H. pylori or H. pylori DNA, was detected using quantitative reverse transcription-polymerase chain reaction and Western blot assays. Then, TLR9 was knocked down through RNA interference technology in MKN45 cells. Cell Counting Kit-8 assay was performed to investigate cell proliferation, and the Transwell system was established to test the migrative and invasive abilities of MKN45 cells. Results: H. pylori infection or H. pylori DNA level was positively correlated with TLR9 upregulation in MKN45 cells. In vitro, H. pylori DNA significantly accelerated cell proliferation and promoted the migration and invasion in MKN45 cells. In contrast, the knockdown of TLR9 significantly suppressed cell proliferation and inhibited the migration and invasion in MKN45 cells. Conclusions: The present results suggest that the H. pylori DNA/TLR9-signaling pathway plays an important role in gastric cancer, which might be a potential therapeutic target.

Recovery of cognitive function after sedation with propofol for outpatient gastrointestinal endoscopy Sanath Allampati, Sijin Wen, Feiyu Liu, Justin T Kupec Saudi Journal of Gastroenterology 2019 25(3):188-193 Background/Aim: Most endoscopies performed in the United States utilize sedation. Anesthesia provides patient comfort and improved procedural quality but adds to the complexity of scheduling routine outpatient procedures. We aimed to assess the return of cognitive function after propofol administration in patients undergoing outpatient endoscopies. Patients and Methods: Cognitive recovery for patients undergoing endoscopy under monitored anesthesia care was evaluated using EncephalApp. Patients were tested before and after procedure and healthy controls were tested twice, 30 min apart. Results were tabulated in on state (on time) and off state (off time) and total time (on time + off time). The time difference between pre- and post-tests, “delta,” was calculated for on, off, and total times. Wilcoxon rank test was used to check the difference in mean delta of all three test times between cases and controls and to check for statistical significance. Results: The difference in mean time between cases and controls was significant for off (P < 0.0001) and total (P = 0.0002) times. No statistically significant difference was noted in mean time for on time (P = 0.013) between cases and controls. Cognitive flexibility, a measure of on time, returned to baseline after procedural sedation even though psychomotor speed, a measure of off time and total time, had not. Conclusion: Cognitive flexibility returns to baseline within 30–45 min after propofol sedation despite delayed return of psychomotor speed and reaction time.

Greater prevalence of comorbidities with increasing age: Cross-sectional analysis of chronic hepatitis B patients in Saudi Arabia Faisal M Sanai, Hamdan Alghamdi, Khalid A Alswat, Mohammed A Babatin, Mona H Ismail, Waleed K Alhamoudi, Abduljaleel M Alalwan, Yaser Dahlan, Abdullah S Alghamdi, Faleh Z Alfaleh, Abdulrahman A Aljumah, Ibrahim H Altraif, Khalid Albeladi, Faisal Batwa, Waleed Alshumrani, Drifa Belhadi, Victor Genestier, Ayman A Abdo Saudi Journal of Gastroenterology 2019 25(3):194-200 Background/Aims: Middle Eastern countries, including Saudi Arabia to some extent, are endemic for chronic hepatitis B (CHB) infection which could be associated with high mortality and comorbidities risk. However, limited data characterizing this CHB population exists. Our aim was to characterize and compare CHB patients in 2015 with those in 2010 and 2012 in Saudi Arabia. Patients and Methods: We conducted and compared three cross-sectional analyses of adult patients with CHB defined as either positive hepatitis B surface antigen or documented CHB history in 2010, 2012, and 2015. Data were accessed from the multicenter Systematic Observatory Liver Disease Registry (SOLID). Results: A total of 765 CHB patients were identified in 2010 (n = 274), 2012 (n = 256), and 2015 (n = 235). Median age was significantly higher in 2015 (47 years) compared to 2010 and 2012 (42 years;P < 0.05). The proportions of patients with hepatocellular carcinoma (range 1–12%) and cirrhosis (range 5–23%) were significantly higher in 2015 compared to 2010 and 2012 (P < 0.05). Compared to 2010, patients in 2015 had significantly (P < 0.05) higher prevalence of coronary artery disease (10% vs. 4%) and hyperbilirubinemia (18% vs. 9%). Although not significant, there was a numerical increase in 2015 in chronic kidney disease (9% vs. 7% in 2010;P= 0.559) and hepatic steatosis (32% vs. 25% in 2010;P= 0.074). Significantly more patients in 2015 (P < 0.05) were treatment experienced (23% vs. 5% in 2010/2012) and switched treatment (17% vs. 1–2% in 2010/2012). Conclusions: Between 2010 and 2015, the CHB population in Saudi Arabia had significantly aged and was more likely to develop liver disease sequelae and other comorbidities.

Bone mineral density loss in patients with cirrhosis Mahmood Dhahir Al-Mendalawi Saudi Journal of Gastroenterology 2019 25(3):201-201