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1.  Colorectal Cancer: A Review of the Genome-wide Association Studies in the Kingdom of Saudi Arabia 
Genome-wise association studies (GWAS) identify risk variants and modifiers that can influence the pathophysiological processes involved in colorectal cancer (CRC) and thus are important to detect associations between disease phenotypes. Our literature review, performed as per PRISMA statement indicates a significant lack of GWAS functional studies in Saudi Arabia. Therefore, studies on sequencing and mapping are needed to identify gene variants that play a role in the pathophysiology of CRC in this specific population. Because it is not apt to generalize disease associations found in other racial and/or ethnic groups to the Arabic or Middle Eastern population, it is very important to conduct GWAS taking into account multiple ethnicities in this region. In addition, linkage studies and case–control studies that include the various confounding and epigenetic factors are needed for appropriate diagnosis of CRC. We recommend that studies in this region be conducted to understand the role of gene–environment interactions across the various ethnic groups, stages of cancer, tumor type, clinical variables, and the population risk to CRC.
PMCID: PMC4455141  PMID: 26021770
Colorectal cancer; GWAS; Saudi Arabia
2.  Extrahepatic Portal Vein Obstruction and Portal Vein Thrombosis in Special Situations: Need for a New Classification 
Extrahepatic portal vein obstruction is a vascular disorder of liver, which results in obstruction and cavernomatous transformation of portal vein with or without the involvement of intrahepatic portal vein, splenic vein, or superior mesenteric vein. Portal vein obstruction due to chronic liver disease, neoplasm, or postsurgery is a separate entity and is not the same as extrahepatic portal vein obstruction. Patients with extrahepatic portal vein obstruction are generally young and belong mostly to Asian countries. It is therefore very important to define portal vein thrombosis as acute or chronic from management point of view. Portal vein thrombosis in certain situations such as liver transplant and postsurgical/liver transplant period is an evolving area and needs extensive research. There is a need for a new classification, which includes all areas of the entity. In the current review, the most recent literature of extrahepatic portal vein obstruction is reviewed and summarized.
PMCID: PMC4455142  PMID: 26021771
Cirrhosis; portal biliopathy; portal vein thrombosis
3.  The Relationship of Circulating Fetuin-A With Liver Histology and Biomarkers of Systemic Inflammation in Nondiabetic Subjects with Nonalcoholic Fatty Liver Disease 
Fetuin-A, a glycoprotein with anti-inflammatory properties, plays an important role in counter-regulating inflammatory responses. It has also been associated with insulin resistance and metabolic syndrome. We aimed to investigate circulating concentrations of fetuin-A and its possible association with hepatic and systemic inflammation in nondiabetic subjects with nonalcoholic fatty liver disease (NAFLD).
Patients and Methods:
We included 105 nondiabetic male subjects with NAFLD [nonalcoholic steatohepatitis (NASH, n = 86) and simple steatosis (SS, n = 19)]. Plasma levels of fetuin-A and markers of inflammation [high-sensitive C reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and adiponectin] were measured by enzyme-linked immunosorbent assay method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index.
Fetuin-A was negatively correlated with age (r = −0.27, P = 0.006), however there was no association between fetuin-A and body mass index, waist circumference (WC), glucose, insulin, HOMA-IR, lipid parameters, and inflammatory markers. In addition, no significant association was observed between fetuin-A and histological findings including liver fibrosis.
This study demonstrated that plasma fetuin-A levels are not correlated with the hepatic histology and systemic markers of inflammation in nondiabetic subjects with NAFLD. Our data also suggested that age is significantly associated with fetuin-A in this clinically relevant condition.
PMCID: PMC4455143  PMID: 26021772
Adiponectin; fetuin-A; inflammation; nonalcoholic fatty liver disease
4.  Virologic Response and Safety of Tenofovir Versus Entecavir in Treatment-Naïve Chronic Hepatitis B patients 
This study aimed to evaluate the antiviral response and safety of tenofovir (TDF) versus entecavir (ETV) in treatment-naïve CHB patients.
Patients and Methods:
We performed a retrospective cohort study of treatment-naive CHB patients who were treated with TDF or ETV. We analyzed virologic, biochemical, and serologic responses at 3, 6, and 12 months.
A total of 107 patients (TDF group = 49, ETV group = 58) were included. Baseline characteristics were similar between the two groups. The estimated proportion of complete virologic response (CVR) in the TDF or ETV group was 44.9% versus 39.7% at 6 months and 89.6% versus 83.2% at 12 months, respectively (P = 0.991). Viral breakthrough was not observed in both groups. One patient in the TDF group and two patients in the ETV group experienced HBeAg loss, respectively (P = 0.657). High HBV DNA level at baseline was a significant negative predictor of virologic response by Cox regression analysis (P = 0.007). The safety profile was similar between the two groups. There was no case with serious adverse event.
Both TDF and ETV were effective in achieving CVR and had a favorable safety profile in treatment-naïve CHB patients. High viral load at baseline was a negative predictive factor of CVR.
PMCID: PMC4455144  PMID: 26021773
Chronic hepatitis B; efficacy; entecavir; safety; tenofovir
5.  Clinical, Endoscopic, and Radiologic Features of Three Subtypes of Achalasia, Classified Using High-Resolution Manometry 
High-resolution manometry (HRM) has improved the accuracy of manometry in detecting achalasia and determining its subtypes. However, the correlation of achalasia subtypes with clinical, endoscopic, and radiologic findings has not been assessed. We aimed to evaluate and compare the clinical, endoscopic, and fluoroscopy findings associated with three subtypes of achalasia using HRM.
Patients and Methods:
The retrospective clinical data, HRM, endoscopy, and radiologic findings were obtained from the medical records of untreated achalasia patients.
From 2011 to 2013, 374 patients underwent HRM. Fifty-two patients (14%) were diagnosed with achalasia, but only 32 (8.5%) of these patients had not received treatment and were therefore included in this study. The endoscopy results were normal in 28% of the patients, and a barium swallow was inconclusive in 31% of the achalasia patients. Ten patients (31%) were classified as having type I achalasia, 17 (53%) were classified as type II, and 5 (16%) were classified as type III. Among the three subtypes, type I patients were on average the youngest and had the longest history of dysphagia, mildest chest pain, most significant weight loss, and most dilated esophagus with residual food. Chest pain was most common in type III patients, and frequently had normal fluoroscopic and endoscopic results.
The clinical, radiologic, and endoscopic findings were not significantly different between patients with type I and type II untreated achalasia. Type III patients had the most severe symptoms and were the most difficult to diagnose based on varied clinical, radiologic, and endoscopic findings.
PMCID: PMC4455145  PMID: 26021774
Achalasia; Chicago classification; high-resolution manometry
6.  γ-Glutamyl Transpeptidase in Men and Alanine Aminotransferase in Women are the Most Suitable Parameters Among Liver Function Tests for the Prediction of Metabolic Syndrome in Nonviral Hepatitis and Nonfatty Liver in the Elderly 
Nonalchoholic fatty liver disease (NAFLD) has been reported as a hepatic manifestation of metabolic syndrome (MetS); it is common and accounts for 80% of the cases with abnormal liver function tests (LFTs). In addition, several studies have proved that there is a correlation between abnormal LFTs and MetS. Therefore, LFTs may represent the abnormal metabolic status of livers in the patients with MetS. To identify the early state of metabolic dysfunction, we investigate the value of LFTs for the future MetS development in the relatively healthy (non-NAFLD) elderly.
Patients and Methods:
A total of 16,912 subjects met the criteria for analysis. In the first stage of this study, subjects were enrolled in the cross-sectional study in order to find out the optimal cutoff value in different LFTs with higher chances to have MetS. In the second stage of the present study, subjects with MetS at baseline were excluded from the same study group, and a median 5.6-year longitudinal study was conducted on the rest of the group.
Among all LFTs, only aspartate aminotransferase in both genders and the α-fetal protein in women failed to show the significance in distinguishing subjects with MetS by the receiver operating characteristic curve. In the Kaplan–Meier plot, only γ-glutamyl transpeptidase (γ-GT) in men and the alanine aminotransferase (ALT) in women could be used to successfully separate subjects with higher risk of developing the MetS from those with lower risk. Finally, in the multivariant Cox regression model, similar results were identified. Still, the hazard ratio (HR) to have future MetS, γ-GT in men, and ALT in women showed significance (HR = 1.511 in men and 1.504 in women).
Among all the different LFTs, γ-GT (>16 U/L) in male and ALT (>21 U/L) in female were the best predictors for the development of MetS in healthy elderly. These two liver markers could be an ancillary test in predicting future MetS development/diagnosis. Elevation of the LFTs without underlying liver diseases should be treated as a warning sign of the possible MetS development in the elderly.
PMCID: PMC4455146  PMID: 26021775
Alanine aminotransferase; elderly; liver function tests; metabolic syndrome; γ-glutamyl transpeptidase
7.  Role of D-dimer in the Development of Portal Vein Thrombosis in Liver Cirrhosis: A Meta-analysis 
Background and Aims:
A meta-analysis was performed to explore the role of the D-dimer in the development of portal vein thrombosis (PVT) in liver cirrhosis.
All papers were searched via PubMed, EMBASE, China National Knowledge Infrastructure, Wan Fang, and VIP databases. A standardized mean difference (SMD) with 95% confidence interval (CI) was pooled.
Overall, 284 studies were initially identified, of which 21 were included. Cirrhotic patients with PVT had a significantly higher D-dimer concentration than those without PVT (pooled SMD = 1.249, 95%CI = 0.740–1.758). After the portal hypertension-related surgery, cirrhotic patients with PVT had a similar preoperative D-dimer concentration to those without PVT (pooled SMD = 0.820, 95%CI = −0.122–0.286), but a higher postoperative value of D-dimer concentration than those without PVT (pooled SMD = 2.505, 95%CI = 0.975–4.036). Notably, the D-dimer concentration at the 1st postoperative day was similar between cirrhotic patients with and without PVT (pooled SMD = 0.137, 95%CI = −0.827–1.101), but that at the 7th post-operative day was higher in cirrhotic patients with PVT than in those without PVT (pooled SMD = 1.224, 95%CI = 0.277–2.171).
D-dimer might be regarded as a diagnostic marker for PVT in liver cirrhosis. In addition, postoperative D-dimer testing is worthwhile for the diagnosis of PVT after portal hypertension-related surgery.
PMCID: PMC4455147  PMID: 26021776
Diagnosis; etiology; predict; portal hypertension
8.  Doxorubicin-loaded Drug-eluting beads Versus Conventional Transarterial Chemoembolization for Nonresectable Hepatocellular Carcinoma 
To compare the efficacy and safety profile of doxorubicin-loaded drug-eluting beads (DEB) to the conventional TACE (C-TACE) in the management of nonresectable hepatocellular carcinoma (HCC).
Patients and Methods:
All patients with nonresectable HCC who underwent either c-TACE or DEB-TACE during the period 2006–2014 and fulfilled the inclusion criteria were included in this retrospective study. Primary endpoints were tumor response rate at first imaging follow up, treatment-related liver toxicity, and treatment emergent adverse events (TEAE).
Thirty-five patients (51 procedures) in the DEB-TACE group and 19 patients (25 procedures) in the c-TACE group were included in the analysis. The median follow up time was 61 days (range 24–538 days) in the DEB-TACE group and 86 days (range 3–152 days) for the c-TACE group patients. Complete response (CR), objective response (OR), disease control (DC), and progressive disease (PD) rates were 11%, 24%, 53%, and 47%, respectively, in the DEB = TACE group compared with 4%, 32%, 64%, and 36%, respectively, in the c-TACE group. Mean ALT change from baseline was minimal in the DEB-TACE patients compared with c-TACE group (7.2 vs 79.4 units, P = 0.001). Hospital stay was significantly shorter in the DEB-TACE group (7.8 days vs 11.4 days; P = 0.038). The 2-year survival rate was 60% for the c-TACE patients and 58% for the DEB-TACE (P = 0.4).
DEB-TACE compared with c-TACE is associated with lesser liver toxicity benefit, better tolerance, and shorter hospital stay. The two modalities however had similar survival and efficacy benefits.
PMCID: PMC4455148  PMID: 26021777
Conventional transarterial chemoembolization; drug-eluting beads; hepatocellular carcinoma
9.  Partially Hydrolyzed Guar Gum in the Treatment of Irritable Bowel Syndrome with Constipation: Effects of Gender, Age, and Body Mass Index 
Partially hydrolyzed guar gum (PHGG) relieves symptoms in constipation-predominant irritable bowel syndrome (IBS) and may have prebiotic properties. However, the correlation between the effectiveness of PHGG and patient characteristics has not been examined. We aimed to investigate the effect of PHGG in symptom relief on constipation-predominant IBS according to gender, age, and body mass index (BMI).
Patients and Methods:
Sixty-eight patients with IBS entered a 2-week run-in period, followed by a 4-week study period with PHGG. Patients completed a daily questionnaire to assess the presence of abdominal pain/discomfort, swelling, and the sensation of incomplete evacuation. The number of evacuations/day, the daily need for laxatives/enemas and stool consistency-form were also evaluated. All patients also underwent a colonic transit time (CTT) evaluation.
PHGG administration was associated with a significant improvement in symptom scores, use of laxatives/enemas, stool form/consistency and CTT. At the end of the study period and compared with baseline, the number of evacuations improved in women, patients aged ≥ 45 years and those with BMI ≥ 25 (P < 0.05 for all comparisons); abdominal bloating improved in males (P < 0.05), patients < 45 years (P < 0.01) and those with BMI < 25 (P < 0.05). A decrease in the number of perceived incomplete evacuations/day was reported in patients with a BMI ≥ 25 (P < 0.05). Reductions in laxative/enema use were recorded in females (P < 0.05), patients < 45 years (P < 0.01), and patients with BMI < 25 (P < 0.05).
Gender, age, and BMI seem to influence the effect of PHGG supplementation in constipated IBS patients. Further studies are needed to clarify the interaction of such parameters with a fiber-enriched diet.
PMCID: PMC4392570  PMID: 25843197
Constipation; guar gum; irritable bowel syndrome
10.  Does Anxiety or Waiting Time Influence Patients' Tolerance of Upper Endoscopy? 
Endoscopy is an essential and very commonly used procedure for the evaluation of a multitude of gastrointestinal symptoms. Although it is increasingly required, patients often wait on arrival at the endoscopy unit until they are called for the procedure. It is not clear whether or not this waiting time may have an impact on patient's tolerance during upper endoscopy. Our study attempts to address this.
Patients and Methods:
We studied consecutive outpatients who underwent endoscopy from September to December, 2013. Gender, age, body mass index (BMI), previous endoscopic experiences, antidepressant therapy, and the time interval between arrival at the endoscopy unit and the onset of examination was recorded. Anxiety before the procedure, pain, and discomfort were rated by a numeric rating scale (0 = no pain/discomfort encountered to 10 = extremely painful/uncomfortable).
One hundred and five consecutive outpatients (male = 52; mean age = 45.3 years; age range = 20–86 years) were included in the study. The mean BMI was 25 ± 4.8; mean waiting time from registration to the procedure was  172 min (time range = 30 - 375 mins). Mean patients' pre-examination anxiety level was 3 ± 3.84, mean discomfort score was 4.3 ± 3.09 and mean pain score was 3.4 ± 3.03. The level of pain and discomfort was significantly higher in patients with higher levels of pre-procedure anxiety. No differences were found in terms of anxiety, pain and discomfort among patients divided according to waiting time.
According to our data, waiting time does not have a significant impact on the perception of pain and discomfort related to the endoscopic procedure. On the other hand, high pre-procedural levels of anxiety were associated with a low tolerance. Further multicenter randomized trials are needed to clarify the impact of waiting time.
PMCID: PMC4392571  PMID: 25843198
Anxiety; discomfort; pain; numeric rating scale; tolerability; upper endoscopy
11.  Cytology Findings in Pancreatic Heterotopia, a Potential Pitfall For Malignancy: A Case Report and Literature Review 
Pancreatic heterotopia is a rare congenital disorder occurring at a variety of sites in the gastrointestinal tract. It is rarely symptomatic. Despite advances in diagnostic techniques, it still remains a challenge to the clinician to differentiate it from a neoplasm. Cytologic characteristics of pancreatic heterotopia in general are rarely described in the literature. We report the cytologic characteristics of heterotopic pancreatic tissue at the gastric outlet in a 48-year-old female. The patient underwent surgical excision due to symptoms related to the lesion. Endoscopic ultrasound fine-needle aspiration is increasingly used for the diagnosis of gastrointestinal tumors, which makes the recognition of certain endoscopically unreachable lesions an important step in optimal patient management.
PMCID: PMC4392572  PMID: 25843199
Cytology of heterotopic pancreas; endoscopic ultrasound-guided fine-needle aspiration; EUS-FNA; heterotopic pancreas; histopathology of ectopic pancreas
16.  Nonalcoholic Fatty Liver Disease: Noninvasive Methods of Diagnosing Hepatic Steatosis 
Hepatic steatosis is the buildup of lipids within hepatocytes. It is the simplest stage in nonalcoholic fatty liver disease (NAFLD). It occurs in approximately 30% of the general population and as much as 90% of the obese population in the United States. It may progress to nonalcoholic steatohepatitis, which is a state of hepatocellular inflammation and damage in response to the accumulated fat. Liver biopsy remains the gold standard tool to diagnose and stage NAFLD. However, it comes with the risk of complications ranging from simple pain to life-threatening bleeding. It is also associated with sampling error. For these reasons, a variety of noninvasive radiological markers, including ultrasound, computed tomography, magnetic resonance spectroscopy, and the controlled attenuation parameter using transient elastography and Xenon-133 scan have been proposed to increase our ability to diagnose NAFLD, hence avoiding liver biopsy. The aim of this review is to discuss the utility and accuracy of using available noninvasive diagnostic modalities for fatty liver in NAFLD.
PMCID: PMC4392577  PMID: 25843191
Hepatic steatosis; nonalcoholic fatty liver; noninvasive methods for hepatic steatosis assessment
17.  Effect of Public Knowledge, Attitudes, and Behavior on Willingness to Undergo Colorectal Cancer Screening Using the Health Belief Model 
Success of colorectal cancer (CRC) screening is dependent in part on the proportion of uptake by the targeted population. We aimed in this study to identify factors that were associated with willingness to undergo CRC screening based on the health belief model (HBM).
Patients and Methods:
This was a cross-sectional study among citizens of Riyadh, Saudi Arabia. Demographic data collected included gender, age, education, marital status, employment status, a history of CRC in the family or knowing a friend with CRC, as well as income. A questionnaire was developed in Arabic based on the HBM and included enquiries on knowledge about CRC symptoms and risk factors, types of CRC screening tests, perceived risk of CRC, previously undergoing CRC screening, intent to undergo CRC screening, perceived barriers to CRC screening, perceived severity of CRC, as well as attitudes toward CRC and its screening.
Five hundred participants were included. The mean age was 41.0 years (SD 10.7). Males were 50% and only 6.7% of those between 50 and 55 years of age had undergone CRC screening. Of those surveyed, 70.7% were willing to undergo CRC screening. Also, 70.5% thought that CRC is curable, 73.3% believed it was preventable, whereas 56.7% thought it was a fatal disease. Neither gender, level of education, occupation, income, marital status, nor general knowledge about CRC was found to be associated with the willingness to undergo CRC screening. Recognizing that colonoscopy was a screening test (OR 1.55, 95% CI; 1.04–2.29) was associated with a strong desire to undergo CRC screening while choosing a stool-based test was associated with not willing to undergo CRC screening (OR 0.59, 95%CI; 0.38–0.91).
We found that the majority of those interviewed were willing to undergo CRC screening and identified a number of barriers as well as potential areas that could be targeted in the promotion of CRC screening uptake if such a national program were to be implemented.
PMCID: PMC4392578  PMID: 25843192
Colon cancer; colonoscopy; early detection; screening; endoscopy; epidemiology; health belief model; Saudi Arabia
18.  Public Awareness of Colorectal Cancer in Saudi Arabia: A Survey of 1070 Participants in Riyadh 
The aim of this study was to investigate colorectal cancer (CRC) awareness in healthy individuals in Saudi Arabia in order to identify segments of the population that would most benefit from targeted education programs.
Setting and Design:
Patients and Methods:
Random, healthy individuals from Riyadh, Saudi Arabia, were approached to participate in a 10-question multiple choice survey about CRC. Data were analyzed by demographic criteria, including age, gender, marital status, and level of education, to determine if members of these groups displayed differential knowledge.
Statistical Analysis:
Differences in responses by demographic data were analyzed using Pearson's Chi-square test. A P < 0.05 was considered statistically significant.
In total, 1070 participants completed the survey. Most respondents believe that screening for colon cancer should begin at symptom onset (42.9%). Less than 20% of all respondents believe that polyps are a risk factor for CRC, which varied significantly according to level of education; however, even the most educated answered correctly less than 50% of the time. Similarly, only 34.8% of all respondents knew that a family history of CRC imparted a personal risk for CRC.
Although older individuals and those with higher education tended to answer questions correctly more often, there were some misconceptions regarding universally accepted screening protocols, symptoms, and general understanding of CRC in Saudi Arabia. A national education/screening program in Saudi Arabia is recommended to improve CRC knowledge.
PMCID: PMC4392579  PMID: 25843193
Colorectal cancer; knowledge; Saudi Arabia; screening; symptoms; survey
19.  Mannose-Binding Lectin Gene Polymorphism and Chronic Hepatitis B Infection in Children 
Mannose-binding lectin (MBL) is a member of innate immune system that activates complement system through lectin pathway. MBL deficiency is associated with susceptibility to infectious diseases. In this study, the relation between MBL gene polymorphism and chronic hepatitis B infection in children is evaluated.
Patients and Methods:
The study included 67 children with chronic hepatitis B and 99 healthy controls. The hepatitis B patients were divided into immuntolerant, chronic inactive, and treatment groups according to their laboratory findings. MBL gene codon 52, 54, and 57 polymorphisms were studied with polymerase chain reaction in all patients and controls. The associations of MBL gene polymorphism with clinical, laboratory, and histopathologic findings were evaluated.
Homozygous codon 54 polymorphism of MBL was found significantly higher in chronic hepatitis B patients than controls. Rate of the polymorphism was similar in all groups and, responsive and nonresponsive patients in the treatment group.
The hepatitis B patients who are homozygous for codon 54 of MBL are prone to develop chronic infection. Longitudinal studies with larger groups are needed.
PMCID: PMC4392580  PMID: 25843194
Childhood; chronic hepatitis B; innate immunity; mannose-binding lectin
20.  Quality of Gastroenterology Research Published in Saudi Arabian Scientific Journals 
Evidence-based medicine has established itself in the field of gastroenterology. In this study we aim to assess the types of study designs of gastroenterology-related articles published in Saudi scientific journals.
Patients and Methods:
An online review using PubMed was carried out to review gastroenterology-related articles published in six Saudi medical journals in the time interval from 2003 to 2012. To classify the level of evidence in these articles we employed the Oxford's levels of evidence. One-way analysis of variance was used to compare the levels of evidence between published articles.
A total of 721 gastroenterology-related articles were reviewed, of which 591 articles met our inclusion criteria; 80.7% were level IV. The three most common types of studies we encountered were cross-sectional (33.9%), case reports (27.9%), and case series (18.8%). Forty-three percent of the published research was in the field of hepatobiliary and spleen. The total number of articles increased from 260 articles in the 1st 5-year period (2003–2007) to 330 in the 2nd period (2008–2012). However, no statistically significant difference in the level of evidence was noted. In Annals of Saudi Medicine Journal, articles with level II increased from 0 to 10% with a P value 0.02.
In our review of gastroenterology-related published articles in Saudi scientific journals, we observed an increase in the quantity of articles with the quality and level of evidence remaining unchanged. Further research is recommended to explore different reasons affecting the volume and quality of gastroenterology-related research in Saudi scientific journals.
PMCID: PMC4392581  PMID: 25843195
Gastroenterology; level of evidence; quality of publications; Saudi Arabia
21.  Toll-Like Receptor Gene Polymorphisms and Susceptibility to Epstein–Barr Virus-Associated and -Negative Gastric Carcinoma in Northern China 
Various polymorphisms in toll-like receptor (TLR) genes have been identified and associated with susceptibility to various malignancies, such as gastric carcinoma (GC), breast cancer, and prostate cancer. However, little is known about the polymorphisms of TLR genes and the susceptibility to GC in Northern China, especially to Epstein–Barr virus-associated GC (EBVaGC). We focused on the association with susceptibility to GC, especially to EBVaGC.
Patients and Methods:
Polymorphisms of the TLR2, 3, 4, and 9 genes were measured in 52 cases of EBVaGC and 157 cases of EBV-negative GC (EBVnGC). Ninety-four peripheral blood samples from healthy individuals were also examined.
For the TLR2 gene (196 to 174 del), there was no significant difference between the GC group and control group in genotype, but there was a significant difference in the del allele. As for the TLR3 gene (c. 1377C/T), there were significant differences between the GC group and the control group in both genotype and allelic frequency. No SNPs single nucleotide polymorphisms (SNPs) were found in the TLR4 gene at the sites Asp299Gly and Thr399Ile. As for TLR9 1486T/C (rs187084) and C2848T (rs352140), there was also no association between the GC group and control. In all of the indicators, there were no significant differences between EBVaGCs and EBVnGCs.
The TLR3 gene (c. 1377C/T) polymorphisms and the del allele of the TLR2 gene (196 to 174) were both associated with susceptibility to GC in Shangdong Province of Northern China. There was no interaction between EBV and TLR gene polymorphisms in EBVaGC.
PMCID: PMC4392582  PMID: 25843196
Epstein–Barr virus-associated gastric carcinoma; Epstein–Barr virus-negative gastric carcinoma; toll-like receptor gene polymorphism
23.  Surgical Treatment for Hepatocellular Carcinoma 
Hepatocellular carcinoma (HCC) is an epithelial tumor derived from hepatocytes; it accounts for 80% of all primary liver cancers and ranks globally as the fourth leading cause of cancer-related deaths. HCC treatment is a multidisciplinary and a multimodal task, with surgery in the form of liver resection and liver transplantation (LT) representing the only potentially curative modality. However, there are variable opinions and discussions about applying these surgical options and using other supporting treatments. This article is a narrative review that includes articles published from 1984 to 2013 located by searching scientific databases such as PubMed, SCOPUS, and Elsevier, with the main keyword of hepatocellular carcinoma in addition to other keywords such as liver transplantation, liver resection, transarterial chemoembolization, portal vein embolization, bridging therapy, and downstaging. In this review, we focus mainly on the surgical treatment options offered for HCC, in order to illustrate the current relevant data available in the literature to help in applying these surgical options and to use other supporting treatment modalities when appropriate.
PMCID: PMC4355856  PMID: 25672233
Bridging therapy; downsizing; hepatocellular carcinoma; liver; liver malignant tumor; liver transplantation; liver resection; transarterial chemoembolization
24.  Sequential Double-Guidewire Technique and Transpancreatic Precut Sphincterotomy for Difficult Biliary Cannulation 
The double-guidewire technique (DGT) and transpancreatic precut sphincterotomy (TPS) are introduced as alternative biliary cannulation techniques for difficult biliary cannulation. This study aimed to evaluate the sequential use of DGT and TPS compared with a needle-knife precut papillotomy (NK).
Patients and Methods:
Six hundred and thirty-five consecutive patients with naοve papilla and who underwent endoscopic retrograde cholangiopancreatography (ERCP) for biliary cannulation from March 2010 to April 2014 in a single institute were analyzed. When standard techniques were unsuccessful, DGT or NK was performed. TPS was sequentially performed if DGT failed.
DGT and NK were attempted in 65 and 58 patients, respectively. A sequential DGT-TPS was performed in 38 patients after a failed DGT. Biliary cannulations were successful in 42%, 74%, and 66% of the DGT, sequential DGT-TPS, and NK patients, respectively (P = 0.002). The cannulation rate was higher in the DGT ± TPS patients (85%) than in the NK patients (P = 0.014). Post-ERCP pancreatitis (PEP) developed in 26% of the successful DGT patients, 37% of the sequential DGT-TPS patients, and 10% of the NK patients (P = 0.008). Of the sequential DGT-TPS patients, the incidence of PEP was significantly reduced in patients with a pancreatic duct (PD) stent compared with patients without a PD stent (24% vs. 62%, P = 0.023).
Sequential DGT-TPS is a useful alternative method compared with NK for patients in whom biliary cannulation is difficult. In the sequential DGT-TPS patients, the incidence of PEP was significantly reduced with the use of a PD stent.
PMCID: PMC4355857  PMID: 25672234
Bile duct; cannulation; endoscopic sphincterotomy; endoscopic retrograde cholangiopancreatography; guidewire
25.  Wire-Guided Cannulation Versus Contrast-guided Cannulation In Pediatric Endoscopic Retrograde Cholangiopancreatography 
Wire-guided cannulation (WGC) of the common bile duct may be associated with fewer complications and higher success rate compared with contrast-guided cannulation (CGC) in adults. Data in children are lacking. The aim of this study was to compare the successful cannulation and complication rate of WGC and CGC in pediatric endoscopic retrograde cholangiopancreatography (ERCP).
Patients and Methods:
We report a retrospective cohort study comparing WGC to CGC in a pediatric cohort. We reviewed the medical records of 167 children who underwent ERCP over a 10-year time period (CGC, 1999-2003, WGC, 2003-2009). Indications, findings, and success were analyzed.
A total of 93 patients (56%) underwent WGC and 74 (44%) CGC. Children in the WGC group were younger (9.5 ± 4.7 vs. 11.5 ± 4.6 years in CGC; P = 0.006) and underwent more therapeutic ERCP interventions (70% vs. 40% in CGC), whereas diagnostic ERCP was more common in the CGC group (60%; P < 0.005). The overall success (96%) and complication rate (8%) were identical in both groups but a trend toward a reduction in the complication rate over time was noted in the WGC group. Post-ERCP pancreatitis (PEP) was documented in one patient in the WGC group (1.1%) and three patients (4.2%) in the CGC group (P-NS).
The success and complication rate in both CGC and WGC are comparable in children but considering the patient and procedure complexity and the trend toward lower PEP in the WGC group, WGC may be the preferable cannulation technique for ERCP in children.
PMCID: PMC4355858  PMID: 25672235
Performance; pediatric endoscopy; pancreatobiliary; technical aspects and complications of ERCP

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