Gastroenterology and Hepatology from Bed to Bench

Endoscopic retrograde cholangiopancreatography (ERCP) has become an essential treatment modality for managing biliary and pancreatic disorders. However, perforation remains one of the most concerning complications associated with ERCP and endoscopic sphincterotomy. While the incidence of perforation following ERCP is relatively low, the associated mortality rate can reach 7.8%. Diagnosis and management of perforations depend on the injury's mechanism, location, and extent, as clinical and radiographic findings suggest. This paper provides a detailed overview of the causes, classification, diagnosis, management, and prevention strategies for ERCP-related perforations.

Microvillus inclusion disease (MVID) is a rare autosomal recessive disease was first discovered in 1978 by Davidson et al with significant mortality and morbidity within the first year of life. Myosin 5B, Syntaxin 3, UNC45A and STXBP2 are the common genetic mutations associated with this disease. It presents with mainly with abdominal symptoms like diarrhoea, abdominal distension, vomiting electrolyte imbalance. Sometimes depending on the genetic mutation involved the phenotypic manifestation can vary. Certain genetic mutations are associated with cholestasis, dilated bowel loops and metabolic acidosis whereas some presents with nystagmus and reduced visual acuity. Electron microscopy of duodenal biopsy sample is used as diagnostic tool. Absence or shortening of apical microvilli with microvillus inclusion bodies in mature enterocytes which are pathognomonic to MVD alongside periodic acid schiff (PAS)-positive granules or vesicles in the immature enterocytes.The mainstay of treatment is long-term total parenteral nutrition. Some cases might require intestinal transplant. However both these treatment options are associated with increased risk complications. Some ground breaking research using active ligands and enteroids can be quite promising options to ameliorate the disease.

Aim: To evaluate the prevalence of primary sclerosing cholangitis (PSC) among Iranian adult patients with inflammatory bowel disease (IBD) or liver disorders.

Background: PSC is a rare and chronic liver disease characterized by inflammation, fibrosis, and intra- and/or extrahepatic bile duct structure.

Methods: A systematic review and meta-analysis was conducted. The Web of Science, Scopus, Pubmed, Embase, Google Scholar, and local databases, including the IranDoc, IranMedex, SID, and MagIran databases, were searched for studies published before 6th February 2023 for the prevalence of PSC among Iranian adults.

Results: In total, 22 articles involving 19,747 Iranian participants were included in this meta-analysis. The overall pooled prevalence of PSC was 8% (95% CI: 5%–12%). Additionally, the prevalence of PSC stratified by gender was calculated based on four studies (n = 1402). The pooled prevalence of PSC was estimated to be 20% (95% CI: 11–31%) in males and 12% (95% CI: 3–38%) in females. The pooled prevalence of PSC was 6% (95% CI: 4–9%) in patients with IBD and 14% (95% CI: 8–23%) in patients with liver transplantation (LT).

Conclusion: The pooled prevalence of PSC was 8% in Iranian adults, and the prevalence was greater in males than in females.

Aim: Thus, this meta-analysis was performed to assess the prognostic value of serum uric acid in patients with gastrointestinal cancers (GI).

Background: There is growing evidence that high serum uric acid may be used as a potential prognostic marker in gastrointestinal malignancies. However, there are inconsistencies in the reported findings.

Methods: Related studies were identified by searching the following databases: PubMed, Web of Science, Cochrane Library, and Scopus, independently up until 30 October 2023. Relevant analyses were carried out to deal with heterogeneity in the data. According to the inclusion criteria, we used English original papers reporting prognostic value of serum/plasma uric acid to determine hazard ratio (HR) and 95% confidence interval (CI) in patients with GI cancers. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to ascertain the association of uric acid levels with gastrointestinal cancer (GI) risk. The inconsistency index (I2) was used to calculate the level of heterogeneity among the selected studies. The quality of each study was evaluated by Newcastle-OTTAWA Scales (NOS).

Results: A total of 9 papers with 95.285 patients were included in this meta-analysis. The findings indicated a significant association between serum uric acid and poor prognosis in patients with gastrointestinal cancers (HR=1.477, 95% CI 1.165-1.873, P= 0.001). Further, in Subgroup analysis we found that patients would have poor survival rate among different cut-offs of uric acid, ≥ 5mg/dl, HR= 1.403, 95% CI=1.150-1.711, P=0.001 vs cut-off <5mg/dl, HR=1.54, 95% CI=1.140-2.063, P=0.005.  

Conclusion: Serum uric acid level is significantly linked to survival outcomes in patients with gastrointestinal cancers. Serum uric acid levels may be an effective prognostic marker associated with clinical outcomes in patients with gastrointestinal cancers. Given the small number of studies included in this meta-analysis and high heterogeneity, we suggest that a more comprehensive study is required to achieve more robust results.

Aim: To compare the efficacy and safety of supraglottic airway (SGA) vs. infraglottic airway (IGA) in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).

Background: To optimize patient outcomes by improving airway control, various airway techniques have been employed for sedation during ERCP. However, there is uncertainty about the noninferiority of SGA devices compared to IGA.

Methods: We performed a systematic review in PubMed, Embase, and Cochrane Library databases, searching for randomized and non-randomized studies comparing SGA vs. IGA in patients undergoing ERCP and reporting at least one of the outcomes of interest. The primary outcomes were procedure time, incidence of hypoxia, and blood staining events. Statistical analyses were performed using R language 4.3.1. Odds ratio (OR) was used for binary outcomes and mean difference (MD) for continuous outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I² statistics.

Results: The study comprised 1 randomized controlled trial (RCT) and 3 observational studies involving 280 patients. Among them, 160 were allocated to the SGA group and 120 to the IGA group. When comparing procedure times, there was no statistically significant difference between SGA and IGA (MD -1.51 minutes; 95% CI -6.10 to 3.09 minutes; p = 0.52; I² = 62%). Regarding blood staining, statistical significance favored IGA over SGA (OR 2.67; 95% CI 1.12 to 6.41, p = 0.027; I² = 0%).

Conclusion: No statistically significant difference in procedure time was observed between SGA and IGA. However, IGA exhibited a favorable outcome regarding reduced blood staining compared to SGA. Further studies comparing similar outcomes are necessary to assess such associations better.

With the growing incidence of colorectal cancer worldwide, mainly due to increased early detection in screening programs, usage of endoscopic techniques for management of colorectal lesions have been gaining progressive attention. Each year, more advanced endoscopic techniques come to practice and old ones find technical enhancements. By reviewing guidelines, randomized controlled trials, meta-analyses, and original research, we aim to establish an evidence-based approach for selecting the optimal endoscopic method based on the polyp size, morphology, and classification. We critically analyze the advantages, limitations, and potential complications associated with each technique, providing a comprehensive overview for clinicians and suggest areas which may yet need further studies to be conducted. Our comprehensive review can provide a framework that will help clinicians choose an approach most suitable for their patients. This review attempts to contribute to the optimization of endoscopic management in colorectal polyps, with eventual improvement in patient outcomes.

Pancreatic cancer (PC) remains one of the most formidable malignancies, with survival rates showing minimal improvement over the years despite progress in chemotherapy, targeted treatments, and radiation therapy. The development of targeted agents and chemotherapy for cancer treatment has only moderately influenced clinical results and has not significantly altered 5-year survival rates. However, with the rapid discovery of the genetic and molecular functions underlying PC, new opportunities for targeted therapies are emerging. One promising approach is oncolytic viral therapy, which has shown potential as a targeted agent for the treatment of pancreatic cancer. Based on the available evidence, oncolytic viral therapy appears to be a viable treatment option for pancreatic cancer. In the present narrative review, we explore oncolytic viruses in detail, and their potential applications in cancer therapy as a future alternative treatment are investigated.

Aim: We aimed to utilize a large-scale database to better understand its efficacy in this subpopulation group.

Background: Constipation is one of the most common gastrointestinal complaints in the United States whose alleviation often requires multiple interventions and behavioral changes. Fruits are often one of the dietary recommendations for constipated patients, but their efficacy remains mixed.

Methods: We examined the nationwide cross-sectional study in the 2006 – 2010 National Health and Nutrition Examination Survey (NHANES) database. Patients over 20 years old were stratified into fruit-consumption and non-fruit-consumption groups. We excluded patients who had intestinal disease, colon cancer, celiac disease, and were pregnant. We used multivariable logistic regression to determine the association between fruit intake and constipation status as recorded in the database.

Results: A total of 12,192 patients were included in our study. The average age was 50.5, and 49.56% of the population are Caucasians, followed by 26.43% of Hispanics; 9.84% had constipation; and 70.04% had fruit consumption. After adjusting for age, gender, ethnicity, education, marital status, poverty ratio, body mass index, food healthy index, physical activity, supplemental usage, medications, smoking, and alcohol usage, patients who had fruit consumption had a lower odd of constipation (aOR 0.83, 95%CI (0.72, 0.95), p=0.008). Further, patients who had larger fruit intake were likely to be less constipated. Post-propensity score matching revealed similar statistically significant.

Conclusion: Fruit intake, as well larger amount of fruit intake, was associated with lesser odds of constipation. Additional investigations in the fruit subtype, as well as the longitudinal relationship, are required to understand this relationship.

Aim: Biofeedback has gained widespread recognition for its ability to facilitate and strengthen pelvic floor muscle function, making it a treatment of choice for these patients.

Background: Fecal incontinence is a common issue among children, particularly those with chronic constipation, significantly affecting both the child's and their family's quality of life. Effective therapeutic interventions are essential to mitigate the symptoms and improve overall well-being. Physiotherapy for pediatric fecal incontinence focuses on strengthening, enhancing endurance, and improving coordination of the anal sphincter and pelvic floor muscles.

Methods: This single-blind clinical trial examined the combined efficacy of Tecar therapy and biofeedback compared to biofeedback alone, with standard medical care serving as the control group. The study included 81 children diagnosed with fecal incontinence. Key outcomes evaluated were the severity of incontinence, severity of constipation, and frequency of incontinence episodes per week. These variables were evaluated before and after a six-week treatment period. Statistical analysis included repeated measures ANOVA for within-group comparisons and one-way ANOVA for between-group comparisons.

Results: The results indicated significant improvements across all measured variables in the intervention groups compared to the control group. Notably, the combination of Tecar therapy and biofeedback outperformed biofeedback alone in certain aspects, such as lowering the severity of incontinence.

Conclusion: The findings underscore physiotherapy as a non-invasive and effective first-line intervention for managing fecal incontinence and chronic constipation in pediatric populations. When feasible, the combination of Tecar therapy and biofeedback is recommended to achieve superior outcomes.

Aim: This study aimed to ascertain the equivalence in meaning and measurement qualities of two assessment tools, namely the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) and Quality of Life (PAGI-QOL), in a sample of individuals with upper gastrointestinal disorders in Iran.

Background: There is substantial demand for reliable and accurate research instruments in researchers' native language to evaluate specific concepts of interest.

Methods: The Rome Foundation Guideline was employed as a framework for this investigation. To this end, a rigorous translation process was utilized, involving forward translation by two independent translators, reconciliation, and backward translation. An expert committee evaluated the semantic, idiomatic, experiential, and conceptual aspects of the translations. A panel of gastroenterologists assessed the content and face validity of the translated questionnaires. Cognitive debriefing sessions were conducted involving patients with dyspepsia or gastroesophageal reflux disease. Concurrent validity of the questionnaires was ascertained by comparing them with the 36-item Short Form Health Survey (SF-36).

Results: The findings presented satisfactory translation of the assessment tools, with initial assessments of internal consistency and construct validity demonstrating suitability. In this particular sample, the internal consistency of the PAGI-SYM was excellent (Cronbach's α range: 0.62-0.92), while the PAGI-QOL indicated good internal consistency (Cronbach's α range: 0.68-0.95). Further, there were strong correlations between the total scores of PAGI-SYM and PAGI-QOL, as well as all SF-36 general health subscale (-0.469 and 0.572, p-value<0.001), demonstrating concurrent validity.

Conclusion: Both PAGI-QOL and PAGI-SYM instruments exhibited validity and reliability when applied to assess upper gastrointestinal disorders.

Aim: This study examined the associations between psychosocial factors, Irritable bowel syndrome (IBS) diagnosis, and quality of life (QOL) in both control and IBS groups. Additionally, we explored the potential influence of psychosocial factors on the onset of IBS and developed a machine-learning model for IBS prediction.

Background: IBS is a prevalent gastrointestinal disorder, with various factors predicting its severity and associated symptoms.

Methods: Through convenience sampling, a cross-sectional study recruited participants diagnosed with IBS (n=134) and healthy controls (n=150) from Arak Gastroenterology Clinics. Linear regression assessed the impact of psychosocial factors on IBS symptom severity and QOL. Logistic regression analyzed the association of these factors with IBS onset. Machine learning algorithms were used to predict IBS based on psychosocial features. Instruments include IBS-SSS, IBS-QOL, Toronto Alexithymia Scale (TAS-20), Visceral Sensitivity Index (VSI), and Pain Catastrophe Scale (PCS).

Results: A total of 284 participants (61.27% females) were recruited in the study, with a mean age of 36.48±10.75 years. Compared to controls, IBS patients exhibited significantly higher scores on measures of pain catastrophizing scale (PCS, 40.95 vs. 27.73), somatization (13.91 vs. 6.49), and alexithymia (60.23 vs. 54.71) as well as lower VSI (40.54 vs. 72.10). For those with IBS, only difficulty identifying feelings and somatization remained associated with worse symptoms, while VSI presented an inverse correlation. Psychological factors were inversely related to QOL. Elevated levels of alexithymia (OR 1.06; 95% CI 0.48, 1.63), somatization (OR 1.80; 95%CI 1.12, 2.48), and PCS (OR 1.70; 95% CI 1.30, 2.10) were associated with a higher chance of developing IBS, while higher VSI (OR -1.65; 95% CI -1.89, -1.42) was protective. Among machine learning models, logistic regression based on these factors (excluding alexithymia) and age achieved good performance (AUC: 0.86, 95% CI: 0.78-0.94; Accuracy: 0.83, 95% CI: 0.73-0.90) in predicting IBS onset.

Conclusion: Psychological factors were linked to worse IBS symptoms and quality of life. A machine learning model for IBS prediction presented promising results.

Aim: This study aimed to analyze trends in the etiologies of liver transplants at Abu Ali Sina Hospital, Shiraz, Iran, from 2020 to 2024.

Background: Liver transplantation (LT) is a crucial treatment for end-stage liver disease (ESLD). Over time, the etiologies leading to LT have evolved due to changes in disease prevalence, advancements in medical treatments, and public health interventions.

Methods: Etiologies of LT were categorized into nine groups: acute liver failure, autoimmune disorders, alcoholic steatohepatitis, liver cancer, vascular, metabolic dysfunction-associated steatohepatitis (MASH), viral hepatitis, metabolic disorders, and others. Trend analysis was performed using Python 3.12 programming language with appropriate libraries.

Results: A total of 1579 patients, 59.9% male with a mean age of 45.12 years (SD: 13.52), were analyzed. Autoimmune disorders emerged as the leading cause of LT, increasing from 32.2% in 2020 to 40.6% in 2024 (p-trend = 0.039). Viral hepatitis cases decreased significantly from 18.1% to 3.0% (p-trend = 0.033). Liver cancer became the third leading cause in 2021, replacing viral hepatitis, while MASH consistently remained the second leading cause.

Conclusion: The significant shifts in LT etiologies underscore the success of public health interventions in reducing the burden of viral-related ESLD. Additionally, the findings highlight the need for ongoing research into the prevention, early diagnosis, and management of autoimmune liver diseases, MASH, and liver cancer. These findings provide critical insights for clinicians and policymakers to enhance liver disease management and allocate resources effectively.