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Biomedicines Oct 2023Pancreatic adenocarcinoma (PDAC) is well known for its poor survival time. Clinical symptoms are painless jaundice or abdominal or back pain. Less specific symptoms... (Review)
Review
Pancreatic adenocarcinoma (PDAC) is well known for its poor survival time. Clinical symptoms are painless jaundice or abdominal or back pain. Less specific symptoms often appear that make diagnosis difficult, e.g., weight loss, loss of appetite, nausea and vomiting, and general weakness. Only 10-20% of patients are diagnosed at an early stage. A cure is practically only possible with a radical surgical operation. In the case of locally advanced findings, neoadjuvant therapy is administered. Among the therapeutic options offered are chemotherapy, radiotherapy (including stereotactic radiotherapy-SBRT), targeted treatment, or immunotherapy. In the case of metastatic disease, of which more than half are present at diagnosis, the goal is to relieve the patient of problems. Metastatic PDAC can cause problems arising from the localization of distant metastases, but it also locally affects the organs it infiltrates. In our review article, we focus on the largest group of patients, those with locally advanced disease and metastatic disease-symptoms related to the infiltration or destruction of the pancreatic parenchyma and the growth of the tumor into the surrounding. Therefore, we deal with biliary or duodenal obstruction, gastric outlet syndrome, bleeding and thromboembolic diseases, pain, depression, and fatigue, as well as pancreatic exocrine insufficiency and malnutrition. Metastatic spread is most often to the liver, peritoneum, or lungs. The presented overview aims to offer current therapeutic options across disciplines. In accordance with modern oncology, a multidisciplinary approach with a procedure tailored to the specific patient remains the gold standard.
PubMed: 37893064
DOI: 10.3390/biomedicines11102690 -
The Journal of Pathology Mar 2024Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies that arise from complex cellular interactions within the tissue microenvironment....
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies that arise from complex cellular interactions within the tissue microenvironment. Here, we sought to decipher tumor-derived signals from the surrounding microenvironment by applying digital spatial profiling (DSP) to hormone-secreting and non-functional GEP-NETs. By combining this approach with in vitro studies of human-derived organoids, we demonstrated the convergence of cell autonomous immune and pro-inflammatory proteins that suggests their role in neuroendocrine differentiation and tumorigenesis. DSP was used to evaluate the expression of 40 neural- and immune-related proteins in surgically resected duodenal and pancreatic NETs (n = 20) primarily consisting of gastrinomas (18/20). A total of 279 regions of interest were examined between tumors, adjacent normal and abnormal-appearing epithelium, and the surrounding stroma. The results were stratified by tissue type and multiple endocrine neoplasia I (MEN1) status, whereas protein expression was validated by immunohistochemistry (IHC). A tumor immune cell autonomous inflammatory signature was further evaluated by IHC and RNAscope, while functional pro-inflammatory signaling was confirmed using patient-derived duodenal organoids. Gastrin-secreting and non-functional pancreatic NETs showed a higher abundance of immune cell markers and immune infiltrate compared with duodenal gastrinomas. Compared with non-MEN1 tumors, MEN1 gastrinomas and preneoplastic lesions showed strong immune exclusion and upregulated expression of neuropathological proteins. Despite a paucity of immune cells, duodenal gastrinomas expressed the pro-inflammatory and pro-neural factor IL-17B. Treatment of human duodenal organoids with IL-17B activated NF-κB and STAT3 signaling and induced the expression of neuroendocrine markers. In conclusion, multiplexed spatial protein analysis identified tissue-specific neuro-immune signatures in GEP-NETs. Duodenal gastrinomas are characterized by an immunologically cold microenvironment that permits cellular reprogramming and neoplastic transformation of the preneoplastic epithelium. Moreover, duodenal gastrinomas cell autonomously express immune and pro-inflammatory factors, including tumor-derived IL-17B, that stimulate the neuroendocrine phenotype. © 2024 The Pathological Society of Great Britain and Ireland.
Topics: Humans; Neuroendocrine Tumors; Gastrinoma; Neuroimmunomodulation; Interleukin-17; Duodenal Neoplasms; Pancreatic Neoplasms; Tumor Microenvironment; Intestinal Neoplasms; Stomach Neoplasms
PubMed: 38229586
DOI: 10.1002/path.6241 -
Frontiers in Immunology 2023The pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous studies have associated gut microbiota with peptic ulcers, the precise nature of the relationship, whether causal or influenced by biases, requires further elucidation.
DESIGN
The largest meta-analysis of genome-wide association studies was conducted by the MiBioGen consortium, which provided the summary statistics of gut microbiota for implementation in the Mendelian randomization (MR) analysis. Summary statistics for five types of PUDs were compiled using the FinnGen Consortium R8 release data. Various statistical techniques, including inverse variance weighting (IVW), MR-Egger, weighted median (WM), weighted mode, and simple mode, were employed to assess the causal relationships between gut microbiota and these five PUDs.
RESULT
In the intestinal microbiome of 119 known genera, we found a total of 14 causal associations with various locations of PUDs and reported the potential pathogenic bacteria of et al. Among them, four had causal relationships with esophageal ulcer, one with gastric ulcer, three with gastroduodenal ulcer, four with duodenal ulcer, and two with gastrojejunal ulcer.
CONCLUSION
In this study, the pathogenic bacterial genera in the gut microbiota that promote the occurrence of PUDs were found to be causally related. There are multiple correlations between intestinal flora and PUDs, overlapping PUDs have overlapping associated genera. The variance in ulcer-related bacterial genera across different locations underscores the potential influence of anatomical locations and physiological functions.
Topics: Humans; Gastrointestinal Microbiome; Ulcer; Genome-Wide Association Study; Mendelian Randomization Analysis; Peptic Ulcer; Stomach Ulcer
PubMed: 37869000
DOI: 10.3389/fimmu.2023.1260780 -
Nature Genetics Dec 2023Peptic ulcer disease (PUD) refers to acid-induced injury of the digestive tract, occurring mainly in the stomach (gastric ulcer (GU)) or duodenum (duodenal ulcer (DU)).... (Meta-Analysis)
Meta-Analysis
Peptic ulcer disease (PUD) refers to acid-induced injury of the digestive tract, occurring mainly in the stomach (gastric ulcer (GU)) or duodenum (duodenal ulcer (DU)). In the present study, we conducted a large-scale, cross-ancestry meta-analysis of PUD combining genome-wide association studies with Japanese and European studies (52,032 cases and 905,344 controls), and discovered 25 new loci highly concordant across ancestries. An examination of GU and DU genetic architecture demonstrated that GUs shared the same risk loci as DUs, although with smaller genetic effect sizes and higher polygenicity than DUs, indicating higher heterogeneity of GUs. Helicobacter pylori (HP)-stratified analysis found an HP-related host genetic locus. Integrative analyses using bulk and single-cell transcriptome profiles highlighted the genetic factors of PUD being enriched in the highly expressed genes in stomach tissues, especially in somatostatin-producing D cells. Our results provide genetic evidence that gastrointestinal cell differentiations and hormone regulations are critical in PUD etiology.
Topics: Humans; East Asian People; Genome-Wide Association Study; Peptic Ulcer; Stomach Ulcer; Duodenal Ulcer
PubMed: 38036781
DOI: 10.1038/s41588-023-01569-7 -
Revista Espanola de Enfermedades... Apr 202459-year-old man, smoker, diabetic and hypertensive. He went to the ER due to fixed abdominal pain in the epigastrium, diaphoresis, dizziness, nausea, and "coffee...
59-year-old man, smoker, diabetic and hypertensive. He went to the ER due to fixed abdominal pain in the epigastrium, diaphoresis, dizziness, nausea, and "coffee grounds" vomiting. On examination he presented abdominal distension and pain on palpation in the epigastrium, without peritonism. He had a BP of 235/100 mmHg and in the blood-tests, leukocytosis with neutrophilia and normal hemoglobin. An urgent abdominal CT scan was performed, identifying a 5x6 cm nodular lesion of homogeneous density attached to the wall of the second and third duodenal portions that compressed the lumen, with two vessels with active bleeding within it. Therefore, percutaneous embolization of the gastroduodenal artery was performed. Subsequently, the patient suffered an episode of severe acute pancreatitis that required ICU admission. Finally, he presented a good clinical evolution with ceasing of pain, complete reabsorption of the hematoma and resolution of the obstructive symptoms.
Topics: Male; Humans; Acute Disease; Pancreatitis; Hematoma; Duodenal Diseases; Gastrointestinal Hemorrhage; Abdominal Pain; Hematemesis
PubMed: 37706445
DOI: 10.17235/reed.2023.9793/2023 -
Journal of Gastrointestinal and Liver... Dec 2023Functional dyspepsia (FD) is a common upper gastrointestinal disorder, characterized by bothersome epigastric pain or burning, fullness after meals or early satiety. The... (Review)
Review
Functional dyspepsia (FD) is a common upper gastrointestinal disorder, characterized by bothersome epigastric pain or burning, fullness after meals or early satiety. The precise pathophysiology remains incompletely understood but may include the role of disordered gut-brain communication leading to disturbances in gastro-duodenal physiological functioning. Even if there are several pharmacological treatment options, it is a chronic and relapsing disorder with persistent symptoms that makes its management difficult. Yoga is a fast-spreading complementary and alternative medicine (CAM) specialty, that has gained attention in the medical field for its ability to address the physical, emotional, mental and social aspects of health and disease. Various other CAM therapies are being used for FD with varying efficacy. However, apart from one research study that used yoga therapy on abdominal pain related functional gastrointestinal disorders in children which included a few FD cases as well (11.6%), no other study using yoga therapy has been done in FD as per our best knowledge. Therefore, in the present review, we have summarized the current scientific understanding of the probable effects of yoga on the pathophysiological mechanisms involved in FD (gastric motility, fundic accommodation, hypersensitivity, duodenal inflammation, psychological distress and gut-brain dysfunction). The literature suggests yoga can have a beneficial role in the management of FD. However, rigorous research and clinical trials are required to confirm the same.
Topics: Child; Humans; Dyspepsia; Yoga; Abdominal Pain; Gastrointestinal Diseases; Postprandial Period
PubMed: 38147600
DOI: 10.15403/jgld-4867 -
Revista Espanola de Enfermedades... Oct 2023Olmesartan-induced enteropathy (OIE) is an emergent enteropathy related to this angiotensin II receptor blocker. Main clinical manifestation is chronic diarrhea and...
Olmesartan-induced enteropathy (OIE) is an emergent enteropathy related to this angiotensin II receptor blocker. Main clinical manifestation is chronic diarrhea and duodenal biopsy is characterized by villous atrophy. Therefore, it is necessary to exclude other causes of enteropathy such as celiac disease, autoimmune enteropathy, intestinal lymphoma, parasitic infections, immunodeficiencies, or Crohn disease. Although it is supposed to be triggered by an immune mechanism, it is not clear its relation to other autoimmune disorders. We report for the first time a case of OIE associated with antiphospholipid syndrome.
PubMed: 36633177
DOI: 10.17235/reed.2022.9427/2022 -
Clinical Otolaryngology : Official... Jul 2023To investigate the association between laryngopharyngeal reflux (LPR), gastroesophageal reflux disease (GERD) and recalcitrant chronic rhinosinusitis (CRS). (Review)
Review
OBJECTIVE
To investigate the association between laryngopharyngeal reflux (LPR), gastroesophageal reflux disease (GERD) and recalcitrant chronic rhinosinusitis (CRS).
DATA SOURCES
PubMed, Cochrane Library and Scopus.
REVIEW METHODS
Three investigators searched the specified databases for studies investigating the relationship between LPR, GERD and recalcitrant CRS with or without polyposis. The following outcomes were investigated with PRISMA criteria: age; gender; reflux and CRS diagnosis; association outcomes and potential treatment outcomes. The authors performed a bias analysis of papers and provided recommendations for future studies.
RESULTS
A total of 17 studies investigated the association between reflux and recalcitrant CRS. According to pharyngeal pH monitoring, 54% of patients with recalcitrant CRS reported hypo or nasopharyngeal acid reflux events. The number of hypo- and nasopharyngeal acid reflux events was significantly higher in patients compared to healthy individuals in 4 and 2 studies, respectively. Only one study did not report intergroup differences. The proportion of GERD was significantly higher in CRS patients compared to controls, with a prevalence ranging from 32% to 91% of cases. No author considered nonacid reflux events. There was significant heterogeneity in the inclusion criteria; definition of reflux and association outcomes, limiting the ability to draw clear conclusions. Pepsin was found in sinonasal secretions more frequently in CRS patients than controls.
CONCLUSION
Laryngopharyngeal reflux and GERD may be contributing factors of CRS therapeutic resistance, but future studies are needed to confirm the association considering nonacid reflux events.
Topics: Humans; Laryngopharyngeal Reflux; Esophagitis, Peptic; Pepsin A; Sinusitis
PubMed: 36895147
DOI: 10.1111/coa.14047 -
Journal of Radiation Research Nov 2023Radiotherapy (RT) has been the standard of care for treating a multitude of cancer types. Radiation-induced gastric injury (RIGI) is a common complication of RT for... (Review)
Review
Radiotherapy (RT) has been the standard of care for treating a multitude of cancer types. Radiation-induced gastric injury (RIGI) is a common complication of RT for thoracic and abdominal tumors. It manifests acutely as radiation gastritis or gastric ulcers, and chronically as chronic atrophic gastritis or intestinal metaplasia. In recent years, studies have shown that intracellular signals such as oxidative stress response, p38/MAPK pathway and transforming growth factor-β signaling pathway are involved in the progression of RIGI. This review also summarized the risk factors, diagnosis and treatment of this disease. However, the root of therapeutic challenges lies in the incomplete understanding of the mechanisms. Here, we also highlight the potential mechanistic, diagnostic and therapeutic directions of RIGI.
Topics: Humans; Gastritis, Atrophic; Risk Factors; Stomach Ulcer; Oxidative Stress; Stomach Neoplasms
PubMed: 37788485
DOI: 10.1093/jrr/rrad071 -
Gut Microbes 2024strains can be broadly classified into two groups based on whether they contain or lack a chromosomal region known as the pathogenicity island ( PAI). Colonization of... (Review)
Review
strains can be broadly classified into two groups based on whether they contain or lack a chromosomal region known as the pathogenicity island ( PAI). Colonization of the human stomach with PAI-positive strains is associated with an increased risk of gastric cancer and peptic ulcer disease, compared to colonization with PAI-negative strains. The PAI encodes a secreted effector protein (CagA) and components of a type IV secretion system (Cag T4SS) that delivers CagA and non-protein substrates into host cells. Animal model experiments indicate that CagA and the Cag T4SS stimulate a gastric mucosal inflammatory response and contribute to the development of gastric cancer. In this review, we discuss recent studies defining structural and functional features of CagA and the Cag T4SS and mechanisms by which strains containing the PAI promote the development of gastric cancer and peptic ulcer disease.
Topics: Animals; Humans; Bacterial Proteins; Antigens, Bacterial; Helicobacter pylori; Stomach Neoplasms; Genomic Islands; Gastrointestinal Microbiome; Peptic Ulcer; Helicobacter Infections
PubMed: 38391242
DOI: 10.1080/19490976.2024.2314201