Gastroenterol. Insights, Volume 15, Issue 2 (June 2024) – 12 articles

In this review article, we summarize the most common clinical manifestations of Primary biliary cholangitis (PBC): pruritus, fatigue, osteoporosis, and dyslipoproteinemia and discuss their impact of the patients’ quality of life. More than half of PBC patients suffer from pruritus or fatigue at the time of diagnosis. We discuss the pathophysiological aspects of the PBC clinical manifestations and treatment options. The pathophysiology of pruritus and fatigue is not adequately elucidated, but IL-31 is associated with the severity of pruritus and could be used to objectify the subjective reporting by questionnaires. Although PBC patients suffer from atherogenic dyslipidemia, they do not seem to have a higher cardiovascular risk; however, this observation needs to be clarified by further clinical studies. The second-line of PBC treatment affects pruritus severity: Obeticholic acid (OCA) worsens pruritus while fibrates improve it. Itching can be alleviated by both non-pharmacological and pharmacological approach, however the are multiple barriers to pharmacological treatment. There is no adequate treatment for fatigue today. Treatment of osteoporosis and dyslipidemia is similar for non-PBC patients; stage of liver disease should be considered in treatment. Further research to clarify the pathophysiology and to eventually discover an effective treatment to improve survival and quality of life (especially pruritus and fatigue) in PBC patients is needed. Full article

Fibroepithelial polyps of the anus (FEPA) are a common benign polypoid proliferation of the stroma covered by squamous epithelium. They are also an often-overlooked part of pathological practice. Currently, immunohistochemistry (IHC) for p16 is the only recommended test for anal intraepithelial neoplasia, but the expression of p16 in stromal multinucleated atypical cells in FEPA has not been described. We aimed to evaluate the expression of p16 in stromal multinucleated atypical cells in FEPA and its role as a diagnostic biomarker to determine the origin of the atypical multinucleated cells in the stroma of FEPA and to rule out the possibility of a neoplastic process. Therefore, we researched a series of 15 FEPA in middle-aged patients histologically and by IHC. Examination of the subepithelial connective tissue from the FEPA showed bizarre, multinucleated cells, while their causal relationship with human papillomavirus (HPV) infection was rejected. In all cases, these cells showed mild to moderate atypical nuclear features and positive expression for p16, while the overlying squamous epithelium was negative. We concluded that FEPA are benign lesions in the stroma where mononuclear and multinucleated (sometimes atypical) cells showing fibroblastic and myofibroblastic differentiation can be found. Nevertheless, we believe that these cells have a practical diagnostic significance, although sometimes the presence of giant cells is difficult to establish, especially in the inflammatory context. The histological similarity between FEPA and normal anal mucosa supports the hypothesis that FEPA may represent the reactive hyperplasia of subepithelial fibrous connective tissue of the anal mucosa. Full article

Background: Acute variceal bleeding (AVB) is a critical complication of portal hypertension, contributing significantly to mortality worldwide. Pharmacological interventions, including terlipressin and octreotide, have evolved to manage AVB, yet consensus on their comparative effectiveness remains elusive. This study conducts a comprehensive systematic review and meta-analysis of randomized control trials (RCTs) comparing terlipressin and octreotide in the management of AVB, aiming to provide insights into their relative benefits. Methods: This study included RCTs with head-to-head comparisons of terlipressin and octreotide. The search strategy covered PubMed, Scopus, and Cinahl databases, and the included studies involved adult patients with confirmed AVB undergoing endoscopic variceal band ligation (EVBL). Results: Seven RCTs meeting inclusion criteria were included in the meta-analysis. The assessed outcomes were: achieving haemostasis within 24 h, rebleeding rate, and mortality rate. The pooled analysis revealed no statistically significant differences between terlipressin and octreotide in achieving haemostasis (OR: 1.30, p = 0.23), rebleeding rates at 5 days (OR: 0.7, p = 0.23), and mortality at 42 days (OR: 0.9, p > 0.5). Conclusion: This meta-analysis suggests that terlipressin and octreotide exhibit similar efficacy in reducing bleeding, rebleeding rates, and mortality when used as adjuvants to EVBL in AVB. Clinicians are encouraged to consider individual patient characteristics and the broader clinical context when choosing between these agents. Future research should focus on addressing existing evidence gaps and enhancing understanding of variables influencing EVBL outcomes. Full article

Background: Vonoprazan-based triple therapy has recently been reported as being more effective than proton pump inhibitors for the eradication of Helicobacter pylori (H. pylori), but it is apparent that the eradication rate could be further improved. Methods: We investigated the effect of the concomitant use of polaprezinc, a therapeutic agent for gastric ulcers, and vonoprazan-based seven-day triple therapy in patients with gastric ulcers compared to standard vonoprazan-based seven-day triple therapy in patients with atrophic gastritis. The regimen for the treatment of atrophic gastritis contained vonoprazan 20 mg, amoxicillin 750 mg, and clarithromycin 200 mg b.d. (VAC group) for seven days; and that for gastric ulcers contained VAC and polaprezinc 75 mg b.d. (VACP group) for seven days. Results: Between October 2021 and January 2023, 201 subjects were examined (VAC group, n = 165; VACP group, n = 36). In per-protocol (PP) analysis, the eradication rate was significantly higher in the VACP group (100%) than in the VAC group (88.2%) (p = 0.025). In patients with severe atrophic gastritis, eradication rates were significantly higher in the VACP group (100%) than in the VAC group (84.4%) in PP analysis. (p = 0.024). Conclusions: The concomitant use of polaprezinc and standard vonoprazan-based first-line eradication therapy is effective for H. pylori. Full article

Clinicians often use endoscopic ultrasonography to survey pancreatic tumors. When endoscopists conduct this examination and find the tumor to be unresectable, a fine-needle biopsy is subsequently performed for tissue confirmation. However, if the tumor is deemed resectable, the necessity of a pre-operative fine-needle biopsy remains debatable. Therefore, we performed a retrospective analysis of a single-center cohort of patients with pancreatic tumors who underwent an endoscopic ultrasound-guided fine-needle biopsy or aspiration (EUS-FNB or FNA) between 2020 and 2022. This study focused on patients diagnosed with resectable malignant pancreatic tumors. The exclusion criteria included individuals diagnosed with benign pancreatic lesions and those with unresectable tumors. A total of 68 patients were enrolled in this study. Histological examination revealed that pancreatic adenocarcinoma was the predominant type of tumor (n = 42, 61.8%), followed by neuroendocrine tumors (n = 22, 32.3%), and metastasis (n = 4, 5.9%). Notably, 17 patients had a history of other cancers, with 23.5% being diagnosed with a metastatic tumor rather than primary pancreatic cancer. Therefore, EUS-FNA/FNB is crucial in patients with a resectable pancreatic tumor and a history of cancer to differentiate between a primary and a metastatic tumor. Full article

Introduction: The current state of pathology practice and the variability in diagnosing pT4a colon cancer have been underexplored in existing studies. Our objective was to establish a specific cutoff point to distinguish between the pathological stages of pT3 and pT4a in colon cancer. Methods: We conducted a cross-sectional study involving pT3 and pT4 (pN0-2, cM0) colon cancers, measuring the distance to the serosa. Patients were categorized and analyzed based on this distance and the peritoneal reaction, with the aim being to ascertain their prognostic implications. Results: A total of 384 patients were analyzed. Patients with a distance between the invading front of cancer and the serosa ≥ 1 mm without a peritoneal reaction exhibited a median survival of 118 months, contrasting the amount of 70 months for those with <1 mm plus peritoneal reaction. Only lengths <1 mm with peritoneal reaction showed a significant correlation with mortality (p < 0.001). Conclusion: Our study revealed that patients in whom neoplastic cells were less than 1 mm from the serosal surface, accompanied by a peritoneal reaction (hemorrhage, inflammation, neovascularization, fibrin), had significantly lower survival rates compared to those with more than 1 mm distance and without peritoneal response (70 vs. 118 months, p < 0.001). Hence, such cases should be considered within the pT4a stage. Full article

Obesity in adolescents is associated with non-communicable risk factors and diseases like metabolic-associated fatty liver disease (MAFLD), which is the liver manifestation of metabolic syndrome. L-citrulline is a non-protein amino acid that has shown positive effects on the degree of steatosis in animals with non-alcoholic fatty liver disease (NAFLD). The aim of the study was to evaluate the effect of oral L-citrulline supplementation on liver function and cardiovascular risk factors in adolescents with abdominal obesity and MAFLD. A prospective, double-blind clinical trial in adolescents with abdominal obesity was randomized into two groups: forty-two adolescents were supplemented with L-citrulline (6 g of L-citrulline/day) (n = 22) and placebo (n = 20) for eight weeks. The variables evaluated were anthropometry, blood pressure, glucose, insulin, HOMA-IR, L-citrulline, L-arginine, malondialdehyde, lipid profile, liver profile, urea, uric acid, and hepatic steatosis by ultrasound. After supplementation, the L-citrulline group had a decrease in liver fat accumulation (p = 0.0007); increases in body weight (p = 0.02), glucose (p = 0.03), and HOMA-IR (p = 0.03); and decreases in BMI (p = 0.002), total cholesterol (p = 0.001), HDL-C (p = 0.01), LDL-C (p = 0.002), and alkaline phosphatase (p = 0.05). L-citrulline for eight weeks decreases hepatic fat accumulation and LDL-C levels in adolescents with abdominal obesity and MAFLD. Full article

We present a multicenter retrospective study of patients undergoing surgery for duodenal adenocarcinoma, from January 2010 to August 2020, in order to determine the epidemiological characteristics and the oncological results after surgical resection obtained in this rare tumor. Variables: demographics; tumor location; surgical intervention and immediate postoperative period; and post-surgical follow-up information, such as recurrence, overall survival (OS), and disease-free survival (DFS). A total of 32 patients underwent surgery. The median age was 69.74 years (IQR 60.47–79.09) and the male/female distribution was 3:1. The surgeries performed were: pancreaticoduodenectomy (PD) in 16 (50%) patients, segmental resection in 13 (40.6%), and the local excision of the lesion in three (9.4%). The R0 rate was higher in PD (86.7% vs. 42.9%; p = 0.013). The OS and DFS rate at one, three and five years was 95%, 70%, and 60% and 86%, 55%, and 48%, respectively. There was a greater trend towards recurrence in patients who did not undergo PD (53.8% vs. 25%; p = 0.14) and conservative surgery seemed to be associated with more local recurrence than PD (57.1% vs. 33.3%; p = 0.49). PD and limited resection are both valid options in the cases of non-ampullary duodenal adenocarcinoma, although PD presented lower rates of loco-regional recurrence. Full article

The pathogenesis of acute and chronic pancreatitis has recently evolved as new findings demonstrate a complex mechanism operating through various pathways. In this review, the current evidence indicating that several mechanisms act in concert to induce and perpetuate pancreatitis were presented. As autophagy is now considered a fundamental mechanism in the pathophysiology of both acute and chronic pancreatitis, the fundamentals of the autophagy pathway were discussed to allow for a better understanding of the pathophysiological mechanisms of pancreatitis. The various aspects of pathogenesis, including trypsinogen activation, ER stress and mitochondrial dysfunction, the implications of inflammation, and macrophage involvement in innate immunity, as well as the significance of pancreatic stellate cells in the development of fibrosis, were also analyzed. Recent findings on exosomes and the miRNA regulatory role were also presented. Finally, the role of autophagy in the protection and aggravation of pancreatitis and possible therapeutic implications were reviewed. Full article

Gastroenterologists are exposed daily to musculoskeletal (MSK) stress during upper and lower gastrointestinal endoscopy, both during routine endoscopies and during long, demanding therapeutic procedures. There is evidence that endoscopy-related MSK injuries are becoming more common, particularly in the back, neck, shoulders, elbows, and hands. The aims of this study were to identify the most stressed muscle groups during endoscopy; to measure their activity using surface electromyographical (EMG) sensors; to detect areas of muscle overload; and to identify the number of microbreaks taken in specific muscles. Furthermore, we measured differences in the loading of these muscle groups with and without the use of special support systems such as a belt-like holder. Measurements were performed on 15 subjects (7 experienced endoscopists and 8 non-endoscopists). Due to this small sample size, inside each group, we achieved inconclusive results regarding statistically significant differences in different muscle groups. We increased the sample size by comparing all participants with and without the belt support system, disregarding their endoscopic background. There was a statistically significant difference (p < 0.05) in muscle tension and in levels of microbreaks in the muscles of the left forearm, biceps, and trapezius muscles. No statistically significant difference was observed in the muscle tension and level of microbreaks in the left deltoid muscle (p > 0.05). We hypothesize that the increased level of muscle loading and decreased level of microbreaks in the deltoid muscle are due to different muscle activity and different shoulder movements. Additionally, the deltoid muscle is not connected to the kinetic chain of body posture and stabilization. It is our belief that MSK injuries in gastrointestinal (GI) endoscopy can be prevented with the use of a belt-like support system. Full article

Introduction. Biliary obstruction is a common manifestation of biliopancreatic malignancies, and its relief is an essential part of the treatment algorithm. Currently, there are three techniques to manage malignant biliary obstruction—endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic biliary drainage (PTBD), and endoscopic ultrasound-guided biliary drainage (EUS-BD). ERCP has been adopted as a first-line treatment modality but EUS-BD is gradually emerging as a viable alternative. The aim of the current article is to assess the clinical outcomes of the three nonsurgical biliary drainage procedures. Materials and methods. A total of 102 consecutive patients with unresectable biliopancreatic malignancy inducing biliary obstruction and subjected to palliative treatment by means of ERCP, EUS-BD, or PTBD were retrospectively included in the study. Results. No difference in clinical and technical success of the procedures was found: ERCP—97.2% technical; 88.9% clinical; PTBD—94.4% technical, 72.2% clinical; EUS-BD—90% technical; 83.3% clinical. Adverse events (AEs) and reinterventions were significantly more common in PTBD (38.9% and 52.8%) and ERCP (27.9% and 25%) compared to EUS-BD (10% and 3.3%). Total duration of hospital stay and number of hospitalizations were lower in the EUS-BD compared to PTBD and ERCP groups. Conclusions. In the presence of adequate expertise, EUS-BD may be superior to PTBD and ERCP in achieving and sustaining biliary drainage in the setting of unresectable malignancy. Full article

Apelin has been implicated in the pathogenesis of several chronic inflammatory diseases through mechanisms related to endothelial cells dysfunction. There is evidence of increased apelin levels in mesenteric adipose tissue and colonic epithelium in patients with inflammatory bowel disease (IBD), but their significance remains unclear. We aimed to measure serum apelin (SA) levels in patients with IBD and to evaluate an association with disease characteristics. SA levels of 104 IBD patients and age and sex matched healthy controls (HCs) in a 1:1 ratio were compared. SA-13 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Mean SA levels were increased in IBD patients compared to HCs (1996.29 ± 1592.96 pg/mL vs. 1552.99 ± 809.64 pg/mL, p = 0.012). Both patients without and with cardiovascular disease (CVD) had increased SA levels (2076.44 ± 1714.74 pg/mL vs. 1525.75 ± 818.74 pg/mL, p = 0.011 and 1743.01 ± 1116.26 pg/mL vs. 1283.92 ± 726.85 pg/mL, p = 0.035, respectively). An inverse association between mean SA levels and a history of musculoskeletal extraintestinal manifestations in the subgroup of IBD patients without CVD was found (p = 0.043). The present study—the first to evaluate SA levels in patients with IBD—showed that IBD patients have higher levels of SA compared to HCs. The potential role of SA in IBD merits further investigation in larger studies. Full article