Frontiers in gastroenterology (Lausanne, Switzerland)最新文献

Background: Health-related quality of life (HRQoL) reflects an individual's perception of how disease and treatment affect their physical, functional, emotional, and social well-being. The burden of cirrhosis is high in Ethiopia but reports on HRQoL among cirrhosis patients are lacking. This study aimed to assess HRQoL and associated factors among patients with cirrhosis at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.

Methods: A cross-sectional study was conducted among 221 patients with cirrhosis at Tikur Anbessa Specialized Hospital. Data were coded and entered into Epi Data 4.6.0.2 and analyzed by STATA software version 17m/p. Bivariable and multivariable linear regression analyses were performed. A p-value lower than 0.05 was used to declare statistical significance.

Results: The mean ± SD age was 42.74 ± 12.25. In multivariable linear regression analysis, Mid Upper Arm Circumference (MUAC) (Standardized β.coff (Std.β.coff) = 0.12, 95% CI (0.06, 0.18), age ≥50 (Std.β.coff = -0.38, 95% CI (-0.68,-0.09), Child-Turcotte-Pugh (CTP) class B (Std.β.coff = -0.92, 95% CI (-1.28, -0.55), CTP class C (Std.β.coff = -1.69, 95% CI (-2.30,-1.07) were significantly associated with mean quality of life score.

Conclusion: Quality of life score was significantly associated with age, CTP class, and MUAC. Health-related quality of life should be taken into consideration in the assessment and treatment of patients with cirrhosis. Older patients, patients with decompensated cirrhosis, and patients with lower MUAC measurements should be given special attention.

Inflammatory Bowel Disease (IBD) is a term used to describe a group of disorders characterized by chronic inflammation of the gastrointestinal tract, with Crohn's Disease (CD) and Ulcerative Colitis (UC) being the most common. While still not fully understood, pathogenesis is believed to be multifactorial - the result of an interplay between genetic susceptibility, immune dysregulation and environmental factors that all lead to chronic inflammation and tissue remodeling. Innate immune cells, which orchestrate the initial defense mechanisms and modulate the subsequent immune response, play a central role in disease initiation and progression. This review examines the complex involvement of innate immune cells in IBD, emphasizing their interactions with environmental factors and the gut microbiome. We highlight the importance of microbial dysbiosis and impaired intestinal barrier function in disease pathogenesis, and the role that innate immune cells play not only as first responders, but also as key players in maintaining intestinal barrier integrity and gut microbiome. This review provides a comprehensive summary of the role that innate immune cells play in IBD pathogenesis with emphasis on the increasingly recognized role of the gut microbiome. A better understanding of innate immune cell mechanisms and of microbiome-immune interactions is key for the development of novel targeted therapies.

Background: Intra-tumoral lymphocytes hold prognostic and predictive significance in colorectal cancer (CRC). The internationally validated Immunoscore™ predicts CRC survival risk by averaging percentile scores of tumor-associated CD3⁺ and CD8⁺ cell densities, but is limited by increased cost, intra-tumoral heterogeneity and omission of other immunologic variables of importance. To address these limitations, we sought to explore alternative prognostic markers based on CD3⁺ and CD8⁺ quantification in CRC.

Methods: 201 resected CRCs were subjected to quantitative CD3/CD8 immunohistochemistry, from which percentile cell counts were averaged ("I-score") in a manner analogous to the Immunoscore™. I-score and exploratory endpoints, including CD3⁺ and CD8⁺ cell densities/percentiles, CD3⁺-CD8⁺ density/percentile differences, and CD3⁺:CD8⁺ density/percentile ratios were tested for association with clinicopathologic and genomic correlates and disease-specific survival (DSS).

Results: CD3⁺ density among CRCs was right-skewed and potentially bimodal, while CD8⁺ density was right-skewed. Density and intra-tumoral variability for CD3⁺ and CD8⁺, as well as combination metrics including I-score, CD3⁺-CD8⁺ density/percentile differences, and CD3⁺-CD8⁺ density/percentile ratios showed distinct clinicopathologic and genomic associations, suggesting that each may hold unique biological significance. CD3⁺ density, CD8⁺ density/percentile, I-score and CD3⁺:CD8⁺ percentile ratio were associated with DSS; only CD3⁺:CD8⁺ percentile ratio was pTNM stage-independent on multivariable analysis. Independently, CD8⁺ density was as prognostic as I-score, questioning the necessity of CD3, or a combination metric.

Conclusions: I-score, in our study, was closely associated with potentially confounding biologic variables such as sex, active smoking, pTNM stage, and mutations in BRAF, and MMR genes. More precise and biologically relevant biomarkers can be achieved by using data-driven CD3⁺/CD8⁺ density cutoffs and ratios, while controlling for important clinicopathologic and molecular variables in CRC. Independent validation and inclusion of other relevant immunocyte types could bring these findings closer to clinical utility in CRC.

Acute Severe Ulcerative Colitis (ASUC) is a well-known and potentially fatal disease state, characterized by symptoms of systemic toxicity including fever, severe anemia, elevated inflammatory markers, and autonomic instability. The life-threatening nature of this condition requires clinicians to make prompt diagnoses and take rapid action, either directing patients towards surgical interventions or medical management. Failure to treat ASUC may lead to toxic dilation of the colon, hemorrhage, or sepsis. Current algorithms suggest the use of intravenous (IV) corticosteroids upon diagnosis, with transition to oral corticosteroids, calcineurin inhibitors or tumor necrosis factor (TNF) inhibitors upon reduction of severe symptoms for candidates deemed to be amenable to medical management. Within these classes, TNF inhibitors such as Infliximab (IFX) have proven to be the most safe, efficacious, and tolerable for patients. While IFX has much data supporting its benefits in achieving short term remission, there are still high rates of long-term need for colectomy and failure to maintain remission. This is due to interactions between the inflamed gastrointestinal tract, the increased metabolic activity seen in ASUC, and intrinsic pharmacodynamic properties of IFX. Certain novel studies suggest that Janus Kinase (JAK-STAT) inhibitors such as Tofacitinib and Upadacitinib are potent agents to salvage clinical remission achieved by IFX, upon its failure. Here we discuss methods to optimize the dosing of IFX to maximize its efficacy, while exploring recent work done on the safety and efficacy of JAK-STAT inhibitors as a salvage therapy, therefore suggesting a novel treatment algorithm to improve clinical outcomes in medically managed ASUC patients.

Hemosuccus pancreaticus is a rare but potentially fatal cause of upper gastrointestinal (GI) bleeding. It is defined as bleeding from the pancreatic duct with blood draining into the duodenum through the ampulla of Vater. In patients with pancreatitis, peri-pancreatic blood vessels may be inflamed by pancreatic enzymes and form a pseudoaneurysm which can rupture and bleed into the pancreatic duct. We report a case of a 43-year-old man who presented with episodic upper GI bleeding of unclear etiology over 9 months without a clear documented history of pancreatitis. The etiology remained elusive even after multiple upper and lower endoscopies. Computed tomography angiography of the abdomen and pelvis during an acute episode detected a pseudoaneurysm of the gastroduodenal artery (GDA) with contrast extravasation into the dilated pancreatic duct. The pseudoaneurysm was treated with coil embolization, resulting in a persisting resolution of the patient's symptoms. Clinicians should consider abdominal angiography when diagnosing obscure GI bleeding.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, and commonly associated with hepatic fibrosis or cirrhosis. This study aims to establish a rat model mimicking the progression from liver fibrosis to cirrhosis and subsequently to HCC using thioacetamide (TAA). We utilized male Lewis rats, treating them with intra-peritoneal injections of TAA. These rats received bi-weekly injections of either 200 mg/kg TAA or saline (as a control) over a period of 34 weeks. The development of cirrhosis and hepatocarcinogenesis was monitored through histopathological examinations, biochemical markers, and immunohistochemical analyses. Our results demonstrated that chronic TAA administration induced cirrhosis aggressive cholangiocarcinoma in addition to well-differentiated HCC, providing a model for early-stage, stage and a mixed liver cancer phenotype. This model is characterized by increased fibrosis, altered liver architecture, and increased hepatocyte proliferation. Biochemical analyses revealed significant alterations in liver function markers, including elevated alpha-fetoprotein (AFP) levels, without affecting kidney function or causing significant weight loss or mortality in rats. This TAA-induced cirrhosis and mixed HCC rat model successfully replicates the clinical progression of human HCC, particularly in terms of liver function impairment and early-stage liver cancer characteristics. It serves as a valuable tool for future research on the mechanisms of antitumor drugs in tumor initiation and development.

Pancreatic schwannomas are exceedingly rare tumors arising from Schwann cells of the peripheral nerve sheath within the pancreas. Often asymptomatic or presenting with nonspecific symptoms, these tumors pose a diagnostic challenge due to their mimicry of other pancreatic neoplasms on imaging studies. Histologically, pancreatic schwannomas demonstrate spindle cell proliferation with a distinct Immunohistochemical profile, including positive staining for S-100 protein. Surgical resection remains the cornerstone of treatment, with excellent long-term prognosis following complete excision. Here, we present a case report of a pancreatic schwannoma in a woman presenting with a cystic pancreatic mass, underscoring the importance of considering this rare entity in the differential diagnosis of pancreatic lesions.

Background: The pancreas plays an important role in the nutrition and metabolism of the whole body. Many disease processes including obesity, diabetes mellitus (DM), acute or chronic pancreatitis, and pancreatic carcinoma result in abnormality of pancreas morphology and function. Magnetic resonance imaging (MRI) provides quantitative parameters including T1, T2, and apparent diffusion coefficient (ADC) values for evaluating normal and abnormal pancreas. Based on the normal range of these quantitative parameters, pancreatic abnormality could be detected early. However, the range and the relationship of T1, T2, and ADC values with gender and age groups using the same dataset have not been explored.

Purpose: To establish the ranges of MRI tissue and functional parameters, including T1, T2, and ADC values, in healthy adult pancreas and their correlations with gender, subregion, and age.

Materials and methods: The T1, T2, and ADC values of healthy pancreas in 86 adults were measured using a 3.0-T MRI scanner. The average T1, T2, and ADC values were obtained in the whole pancreas and subregions (head, neck, body, and tail). Their correlations with gender and age were investigated.

Results: The T1, T2, and ADC values of the whole pancreas from all subjects were 870.07 ± 61.86 ms, 44.07 ± 6.14 ms, and 1.072 ± 0.212 × 10^-3 mm²/s, respectively. T2 values were significantly different between genders (P < 0.05). No significant differences were found between subregions. The T1, T2, and ADC values differed significantly among the age groups (P < 0.05). The T1 value revealed a moderately positive correlation, while the T2 and ADC values displayed negative correlations with age (r = 0.31, -0.45, and -0.39, respectively). The combination of T1, T2, and ADC values achieved the highest AUC value and showed a significant difference compared to T1, T2, and ADC values alone in predicting age older than 45 years.

Conclusion: This study established the normal ranges of T1, T2, and ADC. We found that T2 is different between men and women, and T1, T2, and ADC are age-dependent. These results could be useful for quantitative MRI of pancreatic disease.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, and it is characterized by an excessive hepatic fat accumulation in more than 5% of hepatocytes documented by histology in the absence of alcohol consumption. It is a multifactorial pathology, where genetic component plays a fundamental role: the loss-of-function polymorphisms of genes coding for glutathione S-transferases would predispose to the pathology onset, also in the absence of other risk factors. The aim of the study was to evaluate the relation between the "NULL" GST-T1 and GST-M1 polymorphisms and the onset of NAFLD.

Methods: A group of 117 "apparently healthy" Caucasian volunteers, selected from a larger population through the analysis of previously administered short questionnaires, underwent both magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and buccal swabs: the aim was to identify the possible presence of hepatic steatosis and of the aforementioned "NULL" polymorphisms of interest.

Results: A statistically significant association between the GST-T1 and GST-M1 "NULL" genotypes and the probability of developing NAFLD has been identified. In particular, the GST-T1 "NULL" genotype has been associated with a greater probability of developing steatosis in early age, while the GST-M1 "NULL" genotype seems to increase the risk of developing a higher grade of steatosis. No statistically significant correlations between the "NULL" genotype and sex have been detected.

Discussion: Among the numerous risk factors capable of predisposing to NAFLD onset and progression, the genetic factors seem to play an important role. In particular, GST-T1 and GST-M1 "NULL" polymorphisms would appear to acquire even greater importance, as their loss of function results in an increase of oxidative stress. At high concentrations, ROS can determine oxidative modifications of cellular macromolecules, such as lipids, determining their accumulation into hepatocytes. The study also highlighted the importance of MRI-PDFF for hepatic steatosis diagnosis: this method allows the acquisition of data comparable to those of conventional biopsy; however, it permits the entire liver parenchyma to be visualized.

Conclusion: A statistically significant correlation between the presence of GST-T1 and GST-M1 "NULL" genotypes and the presence of hepatic steatosis has been found.