Navigating the Intersection: Sarcopenia and Sarcopenic Obesity in Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBDs) are intricate systemic conditions that can extend beyond the gastrointestinal tract through both direct and indirect mechanisms. Sarcopenia, characterized by a reduction in muscle mass and strength, often emerges as a consequence of the clinical course of IBDs. Indeed, sarcopenia exhibits a high prevalence in Crohn's disease (52%) and ulcerative colitis (37%). While computed tomography and magnetic resonance imaging remain gold-standard methods for assessing muscle mass, ultrasound is gaining traction as a reliable, cost-effective, and widely available diagnostic method. Muscle strength serves as a key indicator of muscle function, with grip strength test emerging nowadays as the most reliable assessment method. In IBDs, sarcopenia may arise from factors such as inflammation, malnutrition, and gut dysbiosis, leading to the formulation of the 'gut-muscle axis' hypothesis. This condition determines an increased need for surgery with poorer post-surgical outcomes and a reduced response to biological treatments. Sarcopenia and its consequences lead to reduced quality of life (QoL), in addition to the already impaired QoL. Of emerging concern is sarcopenic obesity in IBDs, a challenging condition whose pathogenesis and management are still poorly understood. Resistance exercise and nutritional interventions, particularly those aimed at augmenting protein intake, have demonstrated efficacy in addressing sarcopenia in IBDs. Furthermore, anti-TNF biological therapies showed interesting outcomes in managing this condition. This review seeks to furnish a comprehensive overview of sarcopenia in IBDs, elucidating diagnostic methodologies, pathophysiological mechanisms, and clinical implications and management. Attention will also be paid to sarcopenic obesity, exploring the pathophysiology and possible treatment modalities of this condition.

Fibrostenosing Crohn's Disease: Pathogenetic Mechanisms and New Therapeutic Horizons.

Bowel strictures are well recognized as one of the most severe complications in Crohn's disease, with variable impacts on the prognosis and often needing surgical or endoscopic treatment. Distinguishing inflammatory strictures from fibrotic ones is of primary importance due to the different therapeutic approaches required. Indeed, to better understand the pathogenesis of fibrosis, it is crucial to investigate molecular processes involving genetic factors, cytokines, alteration of the intestinal barrier, and epithelial and endothelial damage, leading to an increase in extracellular matrix synthesis, which ultimately ends in fibrosis. In such a complex mechanism, the gut microbiota also seems to play a role. A better comprehension of molecular processes underlying bowel fibrosis, in addition to radiological and histopathological findings, has led to the identification of high-risk patients for personalized follow-up and testing of new therapies, primarily in preclinical models, targeting specific pathways involving Transforming Growth Factor-ß, interleukins, extracellular matrix balance, and gut microbiota. Our review aims to summarize current evidence about molecular factors involved in intestinal fibrosis' pathogenesis, paving the way for potential diagnostic biomarkers or anti-fibrotic treatments for stricturing Crohn's disease.

Endoscopic Contrast-Enhanced Ultrasound and Fine-Needle Aspiration or Biopsy for the Diagnosis of Pancreatic Solid Lesions: A Systematic Review and Meta-Analysis.

INTRODUCTION: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) are currently recommended for the pathologic diagnosis of pancreatic solid lesions (PSLs). The application of contrast-enhanced endoscopic ultrasound (ECEUS) could aid the endoscopist during an FNA and/or FNB procedure. CEUS is indeed able to better differentiate the pathologic tissue from the surrounding healthy pancreatic parenchyma and to detect necrotic areas and vessels. OBJECTIVES: Our objective was to evaluate if ECEUS could reduce the number of needle passes and side effects and increase the diagnostic efficacy of FNA and/or FNB. METHODS: A comprehensive literature search of clinical studies was performed to explore if ECEUS-FNA or FNB could increase diagnostic accuracy and reduce the number of needle passes and adverse effects compared to standard EUS-FNA or FNB. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned. RESULTS: The proportion of established diagnoses of ECEUS was 90.9% compared to 88.3% of EUS, with no statistically significant difference (p = 0.14). The diagnosis was made through a single step in 70.9% of ECEUS patients and in 65.3% of EUS patients, without statistical significance (p = 0.24). The incidence of adverse reactions was substantially comparable across both groups (p = 0.89). CONCLUSION: ECEUS-FNA and FNB do not appear superior to standard EUS-FNA and FNB for the diagnosis of pancreatic lesions.

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication: A systematic review and meta-analysis.

BACKGROUND: Direct-acting antiviral agents (DAAs) are highly effective treatment for chronic hepatitis C (CHC) with a significant rate of sustained virologic response (SVR). The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression. The assessment of fibrosis degree can be performed with transient elastography, magnetic resonance elastography or shear-wave elastography (SWE). Liver elastography could function as a predictor for hepatocellular carcinoma (HCC) in CHC patients treated with DAAs. AIM: To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus (HCV). METHODS: A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned. RESULTS: At baseline and after 12 wk of follow-up, a trend was shown towards greater liver stiffness (LS) in those who go on to develop HCC compared to those who do not [baseline LS standardized mean difference (SMD): 1.15, 95% confidence interval (95%CI): 020-2.50; LS SMD after 12 wk: 0.83, 95%CI: 0.33-1.98]. The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data. There was a statistically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not (0.64; 95%CI: 0.04-1.24). CONCLUSION: SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs. Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Inflammatory Bowel Diseases and Non-Alcoholic Fatty Liver Disease: Piecing a Complex Puzzle Together.

Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis, are systemic and multifaceted disorders which affect other organs in addition to the gastrointestinal tract in up to 50% of cases. Extraintestinal manifestations may present before or after IBD diagnosis and negatively impact the intestinal disease course and patients' quality of life, often requiring additional diagnostic evaluations or specific treatments. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Current evidence shows an increased prevalence of NAFLD (and its more advanced stages, such as liver fibrosis and steatohepatitis) in IBD patients compared to the general population. Many different IBD-specific etiopathogenetic mechanisms have been hypothesized, including chronic inflammation, malabsorption, previous surgical interventions, changes in fecal microbiota, and drugs. However, the pathophysiological link between these two diseases is still poorly understood. In this review, we aim to provide a comprehensive overview of the potential mechanisms which have been investigated so far and highlight open issues still to be addressed for future studies.

Ultrasound Evaluation of Sarcopenia in Patients with Hepatocellular Carcinoma: A Faster and Easier Way to Detect Patients at Risk.

The condition of sarcopenia, defined as a progressive loss of musculoskeletal mass and muscular strength, is very common in patients with hepatocellular carcinoma (HCC) and presents a remarkable association with its prognosis. Thus, the early identification of sarcopenic patients represents one of the potential new approaches in the global assessment of HCC, and there is increasing interest regarding the potential therapeutic implications of this condition. The gold standard for the quantification of muscle mass is magnetic resonance imaging (MRI) or computed tomography (CT), but these techniques are not always feasible because of the high-cost equipment needed. A new possibility in sarcopenia identification could be muscle ultrasound examination. The measurement of specific parameters such as the muscle thickness, muscular fascicles length or pennation angle has shown a good correlation with CT or MRI values and a good diagnostic accuracy in the detection of sarcopenia. Recently, these results were also confirmed specifically in patients with chronic liver disease. This review summarizes the role of imaging for the diagnosis of sarcopenia in patients with HCC, focusing on the advantages and disadvantages of the diagnostic techniques currently validated for this aim and the future perspectives for the identification of this condition.

Dynamic Contrast-Enhanced Ultrasound in the Prediction of Advanced Hepatocellular Carcinoma Response to Systemic and Locoregional Therapies.

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the sixth most common malignant tumor in the world, with an incidence of 2-8% per year in patients with hepatic cirrhosis or chronic hepatitis. Despite surveillance schedules, it is sometimes diagnosed at an advanced stage, requiring complex therapeutic efforts with both locoregional and systemic treatments. Traditional radiological tools (computed tomography and magnetic resonance) are used for the post-treatment follow-up of HCC. The first follow-up imaging is performed at 4 weeks after resection or locoregional treatments, or after 3 months from the beginning of systemic therapies, and subsequently every 3 months for the first 2 years. For this reason, these radiological methods do not grant the possibility of an early distinction between good and poor therapeutic response. Contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced ultrasound (DCE-US) have gained the interest of several researchers for their potential role in the early assessment of response to locoregional treatments (chemoembolization) or antiangiogenic therapies in patients with advanced HCC. In fact, DCE-US, through a quantitative analysis performed by specific software, allows the construction of time-intensity curves, providing an evaluation of the parameters related to neoplastic tissue perfusion and its potential changes following therapies. It has the invaluable advantage of being easily repeatable, minimally invasive, and able to grant important evaluations regarding patients' survival, essential for well-timed therapeutic changes in case of unsatisfying response, and eventual further treatment planning.

From the Colon to the Liver: How Gut Microbiota May Influence Colorectal Cancer Metastatic Potential.

The gut microbiota's influence on human tumorigenesis is a burning topic in medical research. With the new ontological perspective, which considers the human body and its pathophysiological processes as the result of the interaction between its own eukaryotic cells and prokaryotic microorganisms living in different body niches, great interest has arisen in the role of the gut microbiota on carcinogenesis. Indeed, dysbiosis is currently recognized as a cancer-promoting condition, and multiple molecular mechanisms have been described by which the gut microbiota may drive tumor development, especially colorectal cancer (CRC). Metastatic power is undoubtedly one of the most fearsome features of neoplastic tissues. Therefore, understanding the underlying mechanisms is of utmost importance to improve patients' prognosis. The liver is the most frequent target of CRC metastasis, and new evidence reveals that the gut microbiota may yield an effect on CRC diffusion to the liver, thus defining an intriguing new facet of the so-called "gut-liver axis". In this review, we aim to summarize the most recent data about the microbiota's role in promoting or preventing hepatic metastasis from CRC, highlighting some potential future therapeutic targets.

Ultrasound Elastography to Assess Age of Deep Vein Thrombosis: A Systematic Review.

BACKGROUND AND AIMS: Deep-vein thrombosis (DVT) is a widely diffused condition, and its accurate staging has major clinical and therapeutic implications. Ultrasound elastography (UE) is a rapidly evolving imaging technique that allows quantification of elastic tissue properties and could play a crucial role in determining thrombus age. The aim of this review is to find clinical evidence regarding the application of UE in the evaluation of DVT and its usefulness in differentiating thrombosis age. METHODS: A literature search of clinical studies was performed to identify the ability of UE of discriminate acute, subacute, and chronic DVT. Heterogeneity and publication bias were calculated. In accordance with the study protocol, a qualitative analysis of the evidence was planned. The results were summarized with a comprehensive summary table of study characteristics and baseline characteristics of participant patients. RESULTS: Nine studies matched the predetermined eligibility requirements for this systematic review regarding the risk of bias; the greatest criticalities were found within the domains of patient selection and index test. Based on the quality assessment, two publications were excluded from the qualitative synthesis because of the presence of significant applicability concerns. Among the seven studies that were considered eligible for qualitative synthesis, four evaluated strain elastography and three evaluated shear-wave elastography. Despite significant differences concerning study design, thrombus age definitions, and patient characteristics, nearly all studies demonstrated an increase in thrombus stiffness according to DVT age. CONCLUSIONS: UE could play a key role in routine ultrasound examination of DVT. The measurement of thrombus stiffness has a high biological plausibility and its use is supported by the finding of a correlation between the stiffness and the progression of the DVT age.

Extracellular Vesicles: Novel Potential Therapeutic Agents in Inflammatory Bowel Diseases.

Patients affected by inflammatory bowel diseases (IBD) can nowadays benefit from a growing number of pharmacological options. However, in moderate-to-severe cases, the therapeutic response is still far from optimal, and treatment changes and optimizations are often required. Thus, researchers in this field are strongly engaged in studies aiming to identify new potential therapeutic targets. Extracellular vesicles (EVs) are tiny subcellular bodies with a phospholipid bilayer envelope containing bioactive molecules, which are released from different cells and are involved in intercellular communication. Recent pre-clinical data show their emerging role in the pathogenesis and treatment of IBD. In our review, we summarize current evidence about the function of EVs as active therapeutic agents in ulcerative colitis and Crohn's disease, analyzing the properties of EVs derived from different cellular sources and the mechanisms through which they may improve intestinal inflammation.