Saudi Journal of Gastroenterology
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   Table of Contents - Current issue
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May-June 2022
Volume 28 | Issue 3
Page Nos. 165-246

Online since Thursday, May 12, 2022

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EDITORIAL  

The great wall of inflammatory bowel disease p. 165
Eman Al Sulais, Tim Raine
DOI:10.4103/sjg.sjg_102_22  PMID:35418001
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REVIEW ARTICLE Top

Supragastric belching: Pathogenesis, diagnostic issues and treatment p. 168
Stefan L Popa, Teodora Surdea-Blaga, Liliana David, Mihaela Fadgyas Stanculete, Alina Picos, Dan L Dumitrascu, Giuseppe Chiarioni, Abdulrahman Ismaiel, Dinu I Dumitrascu
DOI:10.4103/sjg.sjg_405_21  
Belching is defined as an audible escape of air from the esophagus or the stomach into the pharynx. It becomes pathologic if it is excessive and becomes bothersome. According to Rome IV diagnostic criteria, there is a belching disorder when one experiences bothersome belching (severe enough to impact on usual activities) more than 3 days a week. Esophageal impedance can differentiate between gastric and supragastric belching. The aim of this review was to provide data on pathogenesis and diagnosis of supragastric belching and study its relationship with gastroesophageal reflux disease and psychological factors. Treatment options for supragastric belching are also presented.
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SYSTEMATIC REVIEW/META-ANALYSIS Top

Comparative effectiveness and tolerability of targeted agents combined with chemotherapy in patients with HER2-positive gastroesophageal cancer: A network meta-analysis p. 175
Yin-Hong Yan, Xiao-Yi Lei, Wei-Ping Hu
DOI:10.4103/sjg.sjg_367_21  PMID:34747874
Background: Gastric cancer (GC) or gastroesophageal junction (GEJ) cancer with HER2 overexpression is highly invasive, with a poor prognosis. With the development of new targeted agents, which agents have ideal therapeutic effects must be determined. This network meta-analysis analyzed the effectiveness and tolerability of targeted agents combined with chemotherapy in HER2-positive GC/GEJ cancer. Methods: Public databases were searched from the date of inception to October 22, 2020. Randomized controlled trials (RCTs) on targeted agent-related regimens for HER2-positive advanced GC or GEJ cancer were included. Subgroup analyses based on publication language, first-line treatment, second/third-line treatment, and HER2 staining intensity were performed. Results: In total, 13 articles were included. The trastuzumabderuxtecan (TraD) and pertuzumab plus trastuzumab and chemotherapy (PerTraChemo) regimens were considered to have high effectiveness but low tolerability. In the subgroup analysis, PerTraChemo still had high effectiveness with low tolerability as the first-line therapy. As the second- or third-line therapy, TraD and lapatinib plus chemotherapy (LapChemo) had high effectiveness and moderate tolerability. In terms of overall survival (OS) time, PerTraChemo had a relative advantage in the immunohistochemistry (IHC) 2+/in situ hybridization (ISH)+ population, whereas TraD, PerTraChemo, and trastuzumab plus chemotherapy (TraChemo) had a relative advantage in the IHC3+ population. Conclusion: TraD had relative advantages as the second- or third-line therapy and in the IHC3 + population. PerTraChemo is a potential first-line therapy, but it requires further confirmation because the JACOB phase III clinical trial failed to confirm the superiority of PerTraChemo over TraChemo with regard to OS.
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ORIGINAL ARTICLES Top

Magnetic resonance enterography and bowel ultrasonography in Saudi Arabian patients with Crohn's disease: A correlation study p. 186
Rani Ahmad, Ahmed Abduljabbar, Mohammad Wazzan, Rawan Thabit, Mahmoud Mosli, Omar I Saadah
DOI:10.4103/sjg.sjg_261_21  PMID:34380869
Background: Crohn's disease (CD) is a complex autoimmune disease that results in chronic inflammation of the gastrointestinal tract. CD activity is determined through clinical, laboratory, endoscopic, and radiological evaluations. Studies that examine the data of radiological modalities of evaluation are lacking, particularly in Saudi Arabia. This study compares magnetic resonance enterography (MRE) and ultrasonography (US) findings among patients diagnosed with CD, to uncover a possible correlation between these techniques. Methods: All patients were assessed for disease activity using MRE and US. Results: A total of 376 patients with CD were recruited. The mean age was 14.9 ± 4.3 years (range, 8–27 years), and males constituted 64% (n = 239) of the cohort. Overall, a strong positive correlation was found between US and MRE evaluations of disease activity (r = 0.83, P < 0.001). US activity correlated positively with MRE findings of enlarged lymph nodes (P < 0.001), bowel wall enhancement (P < 0.001), distal jejunal thickness (P < 0.001), and distal ileal thickness (P < 0.001). The mean difference in wall thickness was significant based on gender (P < 0.001), age in proximal jejunal thickness (P < 0.001), and distal ileal thickness (P = 0.011). Conclusions: MRE and US correlate significantly as imaging techniques for the assessment of CD activity.
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Early discontinuation of biological therapy among inflammatory bowel disease patients in Bahrain: Real world experience p. 193
Maheeba Abdulla, Jehad AlQamish, Nafeesa Mohammed, Mahmood Al Saeed, Hasan Jawad Al Aali, Aysha Al Khaja, Zahra Abdulla Isa Yusuf Hasan, Fatema Yusuf Haider, Sayed Dhiyaa Noor Ebrahim, Zahra Sayed Alawi Mahfoodh, Mahmood Ali Hasan Hubail, Isa Alhajri, Fatema Al-Matrook, Ahmed Tork
DOI:10.4103/sjg.sjg_336_21  PMID:35083972z
Background: Despite the effectiveness of several biological agents in the treatment of inflammatory bowel disease (IBD), some patients respond better than others. Such discrepancies are often evident early in the treatment course. The aim of this study is to identify the risks and assess the rate of early biological discontinuation (BD) among IBD patients. Methods: In this retrospective cohort study conducted in Bahrain all IBD patients who were administered biological agents between June 2009 and June 2019 were included. Medical records were reviewed to collect study data and confirm IBD diagnoses. Early discontinuation of biological agents was defined by discontinuation of a biological agent (within 6 months from administration). Montreal classification was used to classify Crohn's disease and ulcerative colitis (UC) according to location and extension, respectively. Results: Ineffectiveness was the most common reason for early BD. Early BD was not related to the type of IBD, biological agent used, or to most patient-related factors (such as gender and family history). Patient age at index biological initiation was the only independent significant predictor of early BD (P = 0.045, adjusted odds ratios (95% CI): 1.06 (1.001–1.116)] even after correction of two significant factors: comorbid diabetes and marked weight loss at diagnosis. Conclusion: The older the IBD patient at the time of biological therapy initiation, the higher the incidence of early BD. Therefore, caution and close follow-up are required for biological therapy among elderly patients to assess effectiveness and adverse drug reactions.
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Rate and risk factors of postoperative endoscopic recurrence of moderate- to high-risk Crohn's disease patients - A real-world experience from a Middle Eastern cohort p. 201
Nahla Azzam, Yazed AlRuthia, Abdulla Al Thaher, Majid Almadi, Othman Alharbi, Mansour Altuwaijri, Suliman Alshankiti, Mohammed Alanazi, Abdulelah Alanazi, Abdulrahman Aljebreen, Miguel Regueiro
DOI:10.4103/sjg.sjg_499_21  PMID:35042320
Background: Crohn's disease (CD) frequently recurs after intestinal resection. Azathioprine (AZA) and biological therapies have shown efficacy in preventing postoperative recurrence (POR). Data on POR from Middle Eastern populations is lacking. This study aimed to evaluate the rate of endoscopic POR in a cohort of CD patients who underwent ileocecal resection (ICR), and to assess the effectiveness of AZA and biological therapies in reducing the risk of disease recurrence. Methods: We performed a retrospective cohort study on 105 CD patients followed at our center, who underwent ileal resection and were at moderate to high risk for POR. Clinical and laboratory data were collected; the primary endpoint was post ICR endoscopic recurrence at 24 months defined by Rutgeerts' score of i2 or more despite treatment. Results: In total, 105 patients with Crohn's disease met our inclusion criteria; 76.2% were in remission and did not have endoscopic POR at 24 months. Further, 41.9% were on biological therapy, and 34.3% were mainly on AZA. Out of the 28.2% who had POR, approximately 15% were on biological therapies. Penetrating phenotype was the only predictive factor for decreasing POR (OR = 0.19, 95% CI: 0.04–0.98, P = 0.04) as identified in multiple logistic regression analysis. Conclusions: The use of biological therapies post-surgery was not superior than AZA in reducing the endoscopic POR for mod- high risk CD patients. Only penetrating behavior of the CD was associated with significantly lower risk of endoscopic recurrence. This finding is worth further investigation in more robust study designs and among larger samples of patients.
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Melatonin prevents the dysbiosis of intestinal microbiota in sleep-restricted mice by improving oxidative stress and inhibiting inflammation p. 209
Tie Wang, Zixu Wang, Jing Cao, Yulan Dong, Yaoxing Chen
DOI:10.4103/sjg.sjg_110_21  PMID:35259859
Background: Intestinal inflammation caused by sleep restriction (SR) threatens human health. However, radical cure of intestinal inflammatory conditions is considerably difficult. This study focuses on the effect of melatonin on SR-induced intestinal inflammation and microbiota imbalance in mice. Methods: We successfully established a water platform to induce long-term SR in mice for 28 days with or without melatonin supplementation. The SR-induced oxidative stress and inflammatory changes were evaluated in plasma and jejunum tissue samples using in vitro assays. Additionally, changes in the intestinal microbiota were explored using high-throughput sequencing of the 16S rRNA gene. Results: After 20 h of chronic sleep restriction for 28 consecutive days, plasma melatonin was significantly reduced by 48.91% (P < 0.05), while GLU, NE, and CORT were significantly increased (34.32%–90.28%, P < 0.05). The activities of antioxidant enzymes (SOD, GSH-Px, and CAT) and T-AOC in intestinal tissues of SR mice were decreased (17.02%–40.92%, P < 0.05), while the content of MDA was increased (15.12%, P = 0.0089). The levels of pro-inflammatory cytokines (IL-6 and TNF-α) ware increased (65.27%–123.26%, P < 0.05), while the levels of anti-inflammatory cytokines (IL-10 and IFN-γ) were decreased (26.53%–60.41%, P < 0.05). High-throughput pyrosequencing of 16S rRNA from jejunum samples demonstrated an overall increase in the number of OTUs (30.68%, P = 0.015). The α-diversity (Shannon, ACE and Chao1) of jejunum was increased (28.18%–48.95%, P < 0.05), and the β-diversity (PCoA and NMDS) was significantly different from that of the control group (P = 0.001). Furthermore, the prevalences of Helicobacter and Clostridium were higher, whereas that of Bacteroidetes and Lactobacillus were lower in SR mice than in controls (P < 0.05). However, melatonin supplementation reversed the SR-induced changes and improved oxidative stress, inflammatory response, and microbiota dysbiosis in the jejunum, and there was not significant difference compared with the control group (P > 0.05). Conclusions: Melatonin prevents the dysbiosis of intestinal microbiota in SR mice by improving oxidative stress and inhibiting inflammation. Our results may provide a theoretical basis for conducting clinical research on insufficient sleep leading to intestinal health in humans and hence facilitate a better understanding of the role of melatonin.
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Gastrointestinal manifestations of COVID-19 in a single center in the Eastern Province of Saudi Arabia p. 218
Reem J Al Argan, Mona H Ismail, Dania M Alkhafaji, Raed M Alsulaiman, Fatimah E Ismaeel, Reem S AlSulaiman, Ali N Almajid, Lameyaa Alsheekh, Tariq S Alsaif, Alaa A Alzaki, Safi G Alqatari, Abrar J Alwaheed, Abir H Al Said, Marwan J Al Wazzeh, Abdulaziz A AlQurain
DOI:10.4103/sjg.sjg_547_21  PMID:35042321
Background: Several gastrointestinal (GI) symptoms have been associated with novel coronavirus disease-2019 (COVID-19). Their prevalence and relation to the severity and hospital outcome of COVID-19 have not been well reported in the Middle East and Saudi Arabia. We aimed to examine the GI manifestations of COVID-19 and their association with the severity and hospital outcome of COVID-19 infection. Methods: We conducted a retrospective observational study of hospitalized COVID-19 patients who had a positive SARS-COV2 PCR test and were admitted at a university hospital in Saudi Arabia, from March to September 2020. The primary objective of the study was to describe the GI manifestations of COVID-19. The secondary objective was to investigate the association of GI manifestations with severity and outcome of COVID-19 infection. Results: We included 390 patients, of which 111 (28.5%) presented with GI manifestations. The most common presentation was diarrhea followed by nausea, vomiting, and abdominal pain. Patients without GI manifestations had a higher risk of severe-critical COVID-19 infection evident by the development of lung infiltration in more than 50% of lung fields within 24–48 h, acute respiratory distress syndrome, altered mental status, multiorgan failure, and cytokine storm syndrome (P < 0.05). These patients had a higher mortality rate compared to patients with GI manifestations (P = 0.01). A lower odds of death was seen among patients with GI symptoms (AOR 0.36; 95% CI, 0.158–0.82; P = 0.01). Conclusion: COVID-19 infection presents commonly with GI manifestations. Patients with GI manifestations have less severe COVID-19 disease and lower mortality rates.
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The efficacy of Elbasvir/Grazoprevir fixed-dose combination for 8 weeks in HCV treatment and health-related quality of life (HRQoL) in treatment-naïve, non-cirrhotic, genotype 4-infected patients (ELEGANT-4): A single-center, single-arm, open-label, phase 3 trial p. 225
Ahmad AlEid, Areej Al Balkhi, Adel Qutub, Shahem Abbarh, Abed AlLehibi, Abdullah Almtawa, Nawwaf Al Otaibi, Ahmed AlGhamdi, Adel AlGhamdi, Abdulrahman Alamr, Shameem Ahmad, Khalid Al Sayari, Bashaar Al Ibrahim, Abdullah AlKhathlan
DOI:10.4103/sjg.sjg_374_21  PMID:35142658
Background: Cost, adverse events, and long treatment duration can be significant obstacles in treating hepatitis C virus (HCV)-infected individuals. Shortening the treatment regimen can minimize these barriers, thereby enhancing adherence and increasing medication availability to more patients. Methods: This is a single-centre, single-arm, open-label, phase 3 clinical trial on treatment naïve, non-cirrhotic, HCV genotype 4 patients. The study aimed to evaluate an 8-week course of Elbasvir (ELB)/Grazoprevir (GZR) in this population. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR-12). The secondary endpoints were SVR-4, adverse events, and changes in health- and hepatitis-related quality of life (HRQoL). Results: Of the 30 patients who were enrolled, 29 (97%) achieved SVR-12 and SVR-4 (95% CI: 90-100%). No patients experienced serious or life-threatening adverse events (AEs), but mild/moderate AEs were reported by 16 (53%). The most commonly reported AEs were itching/skin rash (20%), headache (16.7%), abdominal/epigastric pain and decreased appetite (13.3% each), and nausea/vomiting (10%). Marked improvements in HRQoL were reported between the first (baseline) and third (SVR-12) timepoints. HRQoL score improvements involved the physical, mental, and hepatitis-specific indices, and ranged between 6 and 42 points (out of 100, P ≤0.003). Conclusion: The trial provides empirical evidence that HCV genotype 4-infected patients can achieve viral eradication with an 8-week-regimen of ELB/GZR. Further, this course of treatment is associated with a minimal adverse event profile and potentially significant improvements in quality of life. (ClinicalTrials.gov number, NCT03578640).
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Serum levels of soluble HLA-G correlate with disease activity in pediatric patients with Crohn's disease p. 233
Murat Cansever, Mehmet Akif Göktaş, Duran Arslan, Türkan Patiroğlu
DOI:10.4103/sjg.sjg_327_21  PMID:35042317
Background: Human leukocyte antigen (HLA)-G, a member of the HLA family, is crucial for fetomaternal tolerance. Transmembrane or circulating/soluble HLA-G (sHLA-G) is elevated in autoimmune conditions and the tumor microenvironment. Circulating sHLA-G levels and their association with disease activity have not yet been assessed in pediatric patients with inflammatory bowel disease (IBD). This study aimed to quantify the serum sHLA-G levels of pediatric patients with IBD and assess the association of serum sHLA-G with disease activity. Methods: We enrolled 24 pediatric IBD patients Crohn's disease (CD) and ulcerative colitis (UC), n = 12 each] and 24 healthy controls. Based on the disease activity index, five and seven of the CD patients had mild and moderate/severe disease, respectively, whereas six of the UC patients were in remission and six had mild disease. Serum was collected and sHLA-G levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: Pediatric patients with CD had significantly higher sHLA-G levels compared with patients with UC and healthy controls. Notably, serum sHLA-G levels were significantly higher in patients with moderate/severe CD than in those with mild CD. Conclusions: Serum sHLA-G levels correlate with disease activity in pediatric patients with CD and are higher in CD patients than in UC patients. Thus, sHLA-G is a potential biomarker for disease activity in CD.
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Actin gamma 1 is a critical regulator of pancreatic ductal adenocarcinoma p. 239
Yichen Tang, Xuehui Peng, Xiaobing Huang, Jing Li
DOI:10.4103/sjg.sjg_356_21  PMID:34856725
Background: Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of pancreatic cancers, which represents one of the most lethal malignancies with a 5-year overall survival less than 10%. Identifying molecular biomarkers is invaluable in helping to predict clinical outcomes and developing targeted chemotherapies. Actin gamma 1 (ACTG1) is a kind of actin isoform that exists in almost all cell types as a component of the cytoskeleton, thus mediating cell viability. Although there have been studies revealing the prognostic significance of ACTG1 in several malignancies such as glioblastoma and hepatocellular carcinoma, its involvement and function in pancreatic cancer needs to be elucidated. Methods: We retrospectively enrolled a cohort of PDAC patients after surgical resection (n = 149) and conducted immunohistochemistry experiments to explore the expression profile of ACTG1. Univariate and multivariate analyses were performed to investigate the clinical relevance of ACTG1. The functional role of ACTG1 in PDAC progression was further validated via both in vitro and in vivo studies. Results: ACTG1 presented a higher expression in PDAC tissues than in nontumorous pancreatic tissues. ACTG1 level positively correlated with tumor stage, implying its potential role as a tumor promoter. Univariate and multivariate analyses identified that patients with lower ACTG1 showed a better overall survival compared to those with higher ACTG1 expression. Cellular and xenograft experiments confirmed the role of ACTG1 on facilitating tumor proliferation both in vitro and in vivo. Conclusions: Our study revealed a pro-oncogenic role of ACTG1 in PDAC, which may help predict prognosis and serve as a novel therapeutic target.
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