Feature Papers in Gastrointestinal Disorders in 2023-2024

Background: Gastric electrical stimulation (GES) therapy is indicated for the treatment of drug-refractory gastroparesis (GP). However, the long-term effects of GES therapy on GP symptom control and identification of the optimal parameters to activate this long-term efficacy have not been investigated. Methods: We conducted a retrospective cohort analysis of 57 GP patients who received GES and pyloroplasty (PP). The interrogation of the GES system and assessment of GP symptoms were conducted at the initiation of GES therapy and during follow-up visits. We determined the changes in GES parameters including voltage (V), impedance (I), and current (C). The outcome was total symptom score (TSS), which was measured by self-reported GP symptoms. Results: The mean age of patients was 44 (±14) years, and 72% were females. The etiology for GP was diabetes mellitus in 72% and idiopathic in 28%. The median duration of GES follow-up was 47 months (range 5–73) A significant decrease was found in individual symptom scores and the TSS (−10.8; 95%CI: −12.6, −9.08) compared to baseline scores (p < 0.0001). During follow-up, readings for I (515 vs. 598 Ω), V (3.3 vs. 4.8 V), and C (6.5 vs. 8.4 mA) significantly increased (p ≤ 0.0001 for all parameters). Higher GES settings were associated with lower TSS in the adjusted analysis (RC, −1.97; 95%CI: −3.81, −0.12, p = 0.037). Conclusions: these findings suggest that adjusting GES parameters over time based on optimizing symptom improvement should be incorporated into the long-term care of patients receiving gastric neurostimulation therapy. Full article

Colorectal cancer (CRC) outcomes in terms of incidence and mortality are significantly worse in African Americans than other Americans. While differences in primary preventions for neoplasia (diet, obesity remediation, aspirin prophylaxis) are being elucidated, genetic mutations affecting premalignant lesions and immune response mechanisms may possibly also explain the increased incidence and mortality, particularly from right-sided disease. Objective: Our team therefore examined colonic segments seeking to test the hypothesis that the immune response and somatic genetic profiles of the colonic anatomic segments may vary and thus account for variations in neoplasia risk among the various colonic segments revealing an antigenic relationship with precancerous lesions. The p87 antigenic field effect is recognized via Adnab-9 antibody immunohistochemistry to be significantly less in the right colon in African Americans, particularly in the cecum. Method: Since small high-grade dysplastic adenomas (SHiGDA) likely missed by CRC screening may progress to cancer, we used Ion Torrent™ sequencing of DNA extracted from four normal colonic segments (two left-sided and two right) of patients with SHiGDAs. We also contrasted unique mutational fields in one patient with a large HiGDA (APC with unique mutations) and one patient who prospectively developed a SHiGDA (JAK3). Result: The SHiGDA (small high-grade dysplastic polyp) patient was p87 negative for any extracted stool, saliva, or colonic effluent via ELISA (enzyme linked immunoadsorbant assay). Furthermore, mean values of expression in segments from the right colon were reduced with respect to the means obtained from the left segments in 233 patients evaluated for a p87 field effect. This has recently been shown to be the case in a large cohort of AA and Caucasian 2294 patients, possibly explaining the right-sided CRC disparity in African Americans and the subsequent increase in mortality. This field effect disparity is also true for two cancers contracted by the SHiGDa patient (lung and prostate). Conclusion: Thus, this pilot study suggests that the reduction in p87 in the right colon is possibly correlated with JAK3 mutations. If confirmed, JAK3 mutations, known to be associated with immune aberrations, may provide a mechanistic explanation for the lack of a p87 (protein 87 kilodaltons) field in some patients with HGD polyps who might benefit from possible intervention such as more intensive screening. Limited microbiome studies were also performed on two patients with familial cancer syndromes and these compared favorably with controls available from the literature. Full article

The management of gastric Helicobacter pylori (H. pylori) infection represents a significant concern in primary healthcare. This survey evaluates the approaches, attitudes, and knowledge regarding gastric H. pylori infection among Italian general practitioners (GPs) and young doctors undergoing general practice training (ITGPs). The survey enrolled 466 GPs and 70 ITGPs. Among GPs, specialist recommendations and the Maastricht–Florence guidelines were frequently referenced sources, while ITGPs relied more on the Maastricht–Florence guidelines and internet resources. ITGPs demonstrated more proactive approaches than GPs in investigating and treating conditions such as gastric ulcers, atrophic gastritis, and iron-deficiency anemia. However, there was limited attention given to the role of H. pylori treatment in first-degree relatives of gastric cancer patients. The most used diagnostic methods were the urea breath test and fecal test. Triple therapy was the most frequently chosen initial treatment regimen, with quadruple bismuth therapy becoming the primary option after initial treatment failure, followed by quinolone therapy and concomitant therapy. This survey underscores a disparity between real-world practices and the recommendations outlined in current guidelines, indicating a need for improved understanding of H. pylori guidelines among both GPs and ITGPs. Full article

The aims of this study were to assess patient-reported outcomes and the survival of patients following curative resection for pancreas cancer. Adult patients undergoing curative pancreatic resection between April 2014 and April 2019 across six major hospitals in Sydney were invited to complete the Short-Form 36 (SF-36v2) and the Functional Assessment Cancer Therapy—Hepatobiliary (FACT-Hep) questionnaires. Time from surgery was categorised into four different time points: 3–11, 12–23, 24–35, and 36–62 months. Survival analyses were performed using Kaplan–Meier and log-rank tests. A total of 278 patients underwent curative resection. Mean (SD) age was 65.0 (13.2), and 50.7% (n = 141) were males. Out of the 205 (74%) alive patients, 128 (62%) completed the study surveys. The physical component score and total FACT-Hep scores showed no significant changes over time. The mental component score improved from 3–11 months to 12–23 months (p = 0.009) and from 3–11 months to 36–62 months (p = 0.007). Survivorship showed a significant difference between malignancy, pre-malignancy, and benign disease groups, with 45.8 months (95%CI: 42.4–49.1), 40.3 months (95%CI: 36.4–44.2), and 41.3 months (95%CI: 37.9–44.9), respectively. For patients undergoing curative resection for pancreatic cancer, mental component scores improved over time, whereas overall survival outcomes seem to be influenced according to cancer pathology. Full article

Background: Gastrointestinal adenocarcinomas are a worldwide and some of the most important causes of death related to cancers. MLH1, PMS2, and K-Ras are some of the main molecules responsible for the control of cellular proliferation. They are widely used as biomarkers for the evaluation of the features of tumoral processes and the clinicopathological characteristics. They depend on the type of cells implied in the tumoral process, and it can be observed in the concentrations of them in different biological fluids. Maspin, also known as peptidase inhibitor 5 or serpin B5 is a tumor suppressor which inhibits invasion and angiogenesis and also regulates apoptosis, but it can also present oncogenic activity depending on tumor location and histology and on the subcellular maspin localization. Its correlations with gastric and colorectal carcinomas have been emphasized in a series of articles, and in this work, a method is used to quantify the concentrations of maspin in three biological fluids, allowing correlations with pathological features. Methods: Patients with their clinical and pathological features were selected from the database of the project GRAPHSENSGASTROINTES and used accordingly with the Ethics committee approval nr. 32647/2018 awarded by the County Emergency Hospital from Targu-Mures. Three kinds of samples have been analyzed (saliva, whole blood, and urine) using a stochastic method using stochastic microsensors. Results: The results obtained using stochastic sensors were correlated with the location of cancer, and there have been elaborated a series of criteria to differentiate gastric cancers from colorectal ones. Conclusions: There can be differentiation between the two types of cancers by using the concentrations of MLH1, PMS2, and K-Ras in saliva and urine samples or the levels of maspin in whole blood and urine or in whole blood, urine, and saliva. The data analysis led to a series of criteria for evaluation of the cancer location. Using only MLH1 and PMS2 concentrations in one of the two kinds of samples was only indicative and did not cover most cases. The use of the criteria only for MLH1 and PMS2 increased the probability of finding out the location, but the best results require the concentrations of K-Ras in the two kinds of samples as additional criteria. Full article

Colorectal cancer is currently a public health concern due to its high incidence, morbidity, and mortality rates. Researchers have identified the intestinal microbiome as a crucial factor in the development of this disease. Currently, specialized literature data support the role of the microbiota in both the development of colorectal cancer and resistance to oncological therapies. Therefore, studying the composition of the gut microbiome can aid in creating risk assessment tools to identify specific populations that would benefit from tailored screening approaches. Also, manipulation of the intestinal microbiome can be useful in improving the response to chemotherapy or immunotherapy. Identifying the pathogenic mechanisms responsible for this causal link can aid in the discovery of novel treatment targets. This article will provide the latest information regarding the influence of the intestinal microbiota on the development and progression of colorectal cancer. Full article

Non-IgE immune-mediated gastrointestinal disorders constitute a heterogeneous group of enigmatic conditions that are on the rise. This category encompasses entities like food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). These are immune-mediated reactions to certain foods without the involvement of allergen-specific IgE in their pathogenesis. Eosinophilic esophagitis (EoE) is also included in this group, acknowledged for its mixed IgE and non-IgE-mediated characteristics. The diagnostic landscape is fraught with challenges, given the poorly understood nature of these disorders and their propensity to manifest with varying and overlapping clinical presentations, typically emerging in infancy with common potential triggers such as cow’s milk and soy. Presently, confirmatory testing for most of these conditions is limited and invasive, emphasizing the pivotal role of a thorough history and physical examination in reaching a diagnosis. Notably, there are limited guidelines for diagnosis and management for most of these disorders. This article elucidates the key distinctions among these disorders, provides an overview of existing diagnostic and therapeutic approaches, and addresses existing knowledge and research gaps. The considerable impact on the quality of life of non-IgE immune-mediated allergic disorders of the gastrointestinal tract, which can result in debilitating complications such as nutritional deficiencies, mental health disorders, and eating disorders, underscores the urgency for comprehensive exploration and management strategies. Full article

Diabetic gastroparesis (DGP) delays gastric emptying in diabetes patients, notably impacting those with type 1 and long-standing type 2 diabetes. Symptoms include early satiety, fullness, appetite loss, bloating, abdominal pain, and vomiting, arising from slow stomach-to-intestine food movement. DGP’s unpredictable nature complicates diagnosis and blood glucose management, leading to severe complications like dehydration, malnutrition, and bezoar formation. Understanding DGP’s mechanisms is crucial for effective management. Vagal dysfunction, disturbances in the interstitial cells of Cajal, reduced neural nitric oxide synthase, and increased oxidative stress contribute to the complex pathophysiology. Accurate diagnosis demands a comprehensive approach, utilizing tools like gastric scintigraphy and the Gastric Emptying Breath Test. Considering the complex relationship between DGP and glycemia, managing blood glucose levels becomes paramount. Nutritional interventions, tailored to each patient, address malnutrition risks, emphasizing smaller, more frequent meals and liquid consistency. DGP’s complex nature necessitates collaborative efforts for enhanced diagnostic strategies, improved pathophysiological understanding, and compassionate management approaches. This comprehensive approach offers hope for a future where individuals with DGP can experience improved well-being and quality of life. Full article

The intestinal microbiota is closely related to liver diseases via the intestinal barrier and bile secretion to the gut. Impairment of the barrier can translocate microbes or their components to the liver where they can contribute to liver damage and fibrosis. The components of the barrier are discussed in this review along with the other elements of the so-called gut–liver axis. This bidirectional relation has been widely studied in alcoholic and non-alcoholic liver disease. However, the involvement of microbiota in the pathogenesis and treatment of viral liver diseases have not been extensively studied, and controversial data have been published. Therefore, we reviewed data regarding the integrity and function of the intestinal barrier and the changes of the intestinal microbioma that contribute to progression of Hepatitis B (HBV) and Hepatitis C (HCV) infection. Their consequences, such as cirrhosis and hepatic encephalopathy, were also discussed in connection with therapeutic interventions such as the effects of antiviral eradication and the use of probiotics that may influence the outcome of liver disease. Profound alterations of the microbioma with significant reduction in microbial diversity and changes in the abundance of both beneficial and pathogenic bacteria were found. Full article

The current management of colorectal cancer liver metastasis (CRCLM) patients involves a multidisciplinary approach, with surgical resection remaining the primary curative option. The advances in liver surgery have improved outcomes, enabling more patients to undergo surgery successfully. In addition, the development of imaging software has improved the preoperative planning and patient selection for surgery and other interventions. Systemic therapies, such as targeted therapies and immunotherapies, have enhanced the chances of complete resection. Targeted agents, in combination with chemotherapy, have shown efficacy in downstaging tumors and increasing resectability. The algorithm approach for these patients continues to evolve, driven by a deeper understanding of the underlying biology. Personalized medicine, guided by molecular profiling and the potential of liquid biopsies in this field, may lead to more tailored treatment strategies. A greater understanding of the immune microenvironment in CRLM may unlock the potential for immune checkpoint inhibitors and novel immunotherapies to become more prominent in the treatment landscape. This review explores the current state-of-the-art treatment of CRCLM and discusses promising future perspectives. Full article

Background: Gastrointestinal angiodysplasia is a significant vascular anomaly characterized by dilated, tortuous blood vessels in the gastrointestinal tract. The current literature extensively documents the association between angiodysplasia and aortic stenosis, known as Heyde syndrome, characterized by the triad of aortic stenosis, GIB, and acquired von Willebrand syndrome. However, other valvular diseases, including mitral and tricuspid regurgitation, have also been implicated. This comprehensive systematic review aims to investigate the spectrum of valvular abnormalities, exploring the intricate mechanisms by which they contribute to gastrointestinal bleeding. Furthermore, it will evaluate the available surgical and nonsurgical treatment modalities, assessing their efficacy in mitigating the incidence of such bleeding. Methods: A comprehensive search of the Pubmed/MEDLINE database was conducted to identify relevant studies to retrieve relevant articles from August 2014 to August 2024. A combination of Medical Subject Heading (MeSH) terms and text words related to cardiac valvular diseases and GIB were used. MeSH terms included “gastrointestinal bleeding”, “heart valve diseases”, “hematochezia”, “heart valve prosthesis”, “bioprosthesis”, “native valve diseases”, and “mechanical valve”. Results: Forty-five papers met the inclusion criteria. Twenty-seven studies covered GIB in aortic valve disease, ten on mitral valve disease, two on tricuspid valve disease, and six on multiple valves. Conclusions: This systematic review demonstrates the association between angiodysplasia and aortic stenosis and highlights mitral regurgitation and tricuspid regurgitation as potential etiologies. Definitive management with valvuloplasty or valve replacement is vital to preventing the onset or recurrence of GIB in patients with valvular disease. Full article

In Europe, transjugular intrahepatic portosystemic shunt (TIPS) is considered the primary treatment for gastric varix (GV) bleeding to reduce portal hypertension. However, in Asian countries, balloon-occluded retrograde transvenous obliteration (BRTO) and its variants plug/coil assisted transvenous retrograde obliteration (PARTO/CARTO) are the preferred approaches. The purpose of this study is to report a European single-center experience in the use of PARTO/CARTO techniques for the treatment of GVs in patients with portal hypertension, focusing on the effectiveness and safety of the procedure. All the procedures involving the PARTO/CARTO techniques performed from 2019 to 2023 were retrospectively evaluated. Technical success was defined as the complete obliteration of both the GVs and the gastro-renal (GR) shunt on review of the Computed Tomography (CT) scan performed 3 days after the procedure. The obliteration rate was also evaluated through performing CT scans 1 and 12 months after the procedure, and through endoscopic follow-up at 3 and 6 months. Additionally, major and minor complications were reported. The study involved seven patients, with a technical success of 100%. During follow-up, there were no episodes of variceal rebleeding or upper gastrointestinal bleeding. Two patients developed ascites, which resolved with medical therapy. One patient exhibited focal portal thrombosis, which was successfully treated with heparin. PARTO/CARTO techniques demonstrated high technical and clinical success rates, offering advantages over traditional BRTO. The use of coils and plugs simplifies the procedure, eliminates sclerosing agents, and prevents complications associated with balloon guiding catheters. Full article

Purpose: Food insecurity and colorectal cancer (CRC) are widely prevalent problems in the U.S. However, the long-term effects of food insecurity among people living with CRC are not well explored (e.g., risk of mortality). Methods: Data from the U.S. National Health and Nutrition Examination Survey (years 1999–2010) were linked with mortality data from the National Death Index up to 31 December 2019. Results: A total of 30,752 adults comprised the analytic sample; 222 were living with CRC and more than a tenth were food-insecure (11.6%). In our adjusted analysis, individuals who were food insecure and had CRC were 4.13 times more likely to die of any cause and 9.57 times more likely to die of cardiovascular diseases (compared to those without CRC and food insecurity). Conclusions: Colorectal cancer is among the top cancers diagnosed in American adults and more than a tenth of adult Americans with CRC live with food insecurity. Given the higher risk of mortality with co-occurring CRC and food insecurity, collaborative healthcare models can help address food insecurity and other social needs of people with CRC, and surveillance measures for food insecurity should be widely implemented across health systems. Full article

Background: Previous systematic reviews have found insufficient and conflicting evidence for an association between the clinical and radiographic diagnosis of functional constipation. Abdominal X-ray is frequently used for the diagnosis of functional constipation in clinical practice. The objective of this study was to evaluate the diagnostic accuracy of abdominal X-ray for the evaluation of functional constipation in children. Results: Three studies were included in the final qualitative analysis. They were heterogeneous in their study design, definition of constipation, and radiologic parameters used to evaluate the abdominal X-rays. Sensitivities ranged from 73–92%, specificities ranged from 26–92%, and diagnostic accuracies ranged from 78–90%. Methods: This study involved a systematic review of English literature published between 2012 and 2022 covering children 2–18 years of age with a diagnosis of functional constipation in whom abdominal X-ray was performed. The databases searched include Medline, Embase, and Scopus. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) guidelines were followed. PROSPERO ID: CRD42022301833. Conclusions: There is insufficient evidence to support the use of abdominal X-ray as part of the diagnostic workup of functional constipation. More methodologically rigorous studies are needed to determine the utility of abdominal X-ray in the evaluation of functional constipation. The diagnosis of functional constipation should be based on history and clinical findings. Full article