Advancements in hepatocellular carcinoma management: the role of 18F-FDG PET-CT in diagnosing portal vein tumor thrombosis.

Portal vein thrombosis, a relatively frequent complication associated with hepatocellular carcinoma (HCC) and liver cirrhosis, is recognized as a significant global health concern. This is mainly due to these conditions' high prevalence and potentially severe outcomes. The aim of our study was to conduct a comprehensive literature review to evaluate the efficacy, accuracy, and clinical implications of 18F-FDG PET-CT in diagnosing and managing portal vein tumor thrombosis (PVTT) in patients with HCC. HCC, which accounts for 80% of liver malignancies, ranks as the fourth most prevalent cancer globally and is a significant contributor to cancer-related mortality. The majority of HCC patients are diagnosed at an advanced stage, leading to a deterioration in patient outcomes. Involvement of the portal vein is also a significant negative factor. This review analyzes the application of 18F-FDG PET-CT in the detection and management of PVTT in patients with HCC, with an emphasis on the importance of the maximum standardized uptake value as an essential diagnostic and prognostic marker. 18F-FDG PET-CT is invaluable for detecting recurrence and guiding management strategies, particularly in patients with high-grade HCC, and plays a pivotal role in differentiating malignant portal vein thrombi from their benign counterparts.

Berberine Effects in Pre-Fibrotic Stages of Non-Alcoholic Fatty Liver Disease-Clinical and Pre-Clinical Overview and Systematic Review of the Literature.

Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis, steatohepatitis, cirrhosis related to non-alcoholic steatohepatitis, and the potential occurrence of hepatocellular carcinoma. In our systematic review, we searched two databases, Medline (via Pubmed Central) and Scopus, from inception to 5 February 2024, and included 73 types of research (nine clinical studies and 64 pre-clinical studies) from 2854 published papers. Our extensive research highlights the impact of Berberine on NAFLD pathophysiology mechanisms, such as Adenosine Monophosphate-Activated Protein Kinase (AMPK), gut dysbiosis, peroxisome proliferator-activated receptor (PPAR), Sirtuins, and inflammasome. Studies involving human subjects showed a measurable reduction of liver fat in addition to improved profiles of serum lipids and hepatic enzymes. While current drugs for NAFLD treatment are either scarce or still in development or launch phases, Berberine presents a promising profile. However, improvements in its formulation are necessary to enhance the bioavailability of this natural substance.

Correlation between Trabecular Bone Score and Homocysteine Level in Rheumatoid Arthritis Patients on Anti-TNF Inhibitors.

Rheumatoid arthritis (RA) is an independent osteoporosis risk factor. Biologic and immunosuppressive treatment, and levels of homocysteine and 25-OH vitamin D may influence the trabecular bone score (TBS) in RA patients. We aimed to compare the effects of biological (b) and conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) on TBS in patients with RA and hyperhomocysteinemia (HHcy) or 25-OH vitamin D deficiency. Patients who had tests conducted for trabecular bone score, bone mineral density (BMD), homocysteine (Hcy) and 25-OH vitamin D at an interval of one year and met the inclusion criteria were enrolled in this retrospective study. Sixty-four patients with RA were enrolled and were divided into the following two groups: the first group (34 patients) had received treatment with bDMARDs and the second group (30 patients) had received csDMARDs. BDMARDs and csDMARDs had a positive influence on TBS and BMD. The best results were observed in the Adalimumab group (p = 0.033). Hyperhomocysteinemia and 25-OH vitamin D deficiency led to lower TBS values. Both bDMARDs and csDMARDs positively affected TBS and BMD in RA patients. High homocysteine serum levels or 25-OH vitamin D deficiency had a negative impact on TBS and BMD after 12 months. Our study aims to show the potential benefits of anti-TNF α drugs on TBS. This impact appears to be strongly associated with serum 25-OH vitamin D and homocysteine levels. Anti-TNF drugs may increase bone mineral density and microstructure. As a result, they may minimize the incidence of fractures in RA patients.

Ferritin and Ferritin-to-Hemoglobin Ratio as Promising Prognostic Biomarkers of Severity in Acute Pancreatitis-A Cohort Study.

BACKGROUND: Acute pancreatitis is an inflammation of the pancreas with variable outcomes depending on its severity. Multiple systems of prediction have been proposed, each with variable specificity and sensitivity and with uneven clinical use. Ferritin is a versatile protein associated with various acute and chronic conditions. AIMS: In our study, we aimed to assess the association of serum ferritin and the ferritin-to-hemoglobin ratio (FHR) with the severity of acute pancreatitis. METHODS: A retrospective study was conducted in our hospital from January 2020 to September 2022 and included 116 patients with acute pancreatitis (graded according to the revised Atlanta classification). Serum ferritin and FHR were determined next to established laboratory parameters in the first 24 h following admission (hematological parameters, amylase, lipase, C-reactive protein, D-dimers, lactate dehydrogenase). We performed a receiver operating characteristic curve analysis for potential predictors. Also, we made correlations and conducted univariate and multivariate analyses for all potential severity biomarkers. RESULTS: The median values of serum ferritin and FHR differed significantly between patients with severe acute pancreatitis and mild cases (serum ferritin: 352.40 vs. 197.35 ng/mL, p = 0.011; FHR: 23.73 vs. 13.74, p = 0.002) and between patients with organ failure and those without organ failure (serum ferritin: 613.45 vs. 279.65 ng/mL, p = 0.000; FHR: 48.12 vs. 18.64, p = 0.000). The medians of the serum ferritin and FHR levels were significantly higher in non-survivors compared with survivors (serum ferritin: 717.71 vs. 305.67 ng/mL, p = 0.013; FHR: 52.73 vs. 19.58, p = 0.016). Serum ferritin and FHR were good predictors for organ failure and mortality, next to D-dimers and procalcitonin (AUC > 0.753 for organ failure and AUC > 0.794 for mortality). In univariate regression analysis, serum ferritin and FHR were independent variables for moderate-severe forms of acute pancreatitis. Still, adjusting the multivariate analysis, only FHR remained a significant predictor. The cut-offs for serum ferritin and FHR for predicting organ failure were 437.81 ng/mL (sensitivity, 71%; specificity, 75%) and 45.63 (sensitivity, 61%; specificity, 88%), and those for mortality during hospitalization were 516 ng/mL (sensitivity, 83%; specificity, 74%) and 51.58 (sensitivity, 66%; specificity, 86%). CONCLUSIONS: Serum ferritin and the ferritin-to-hemoglobin ratio stood out in this study as valuable and accessible predictors of disease severity in the early assessment of acute pancreatitis, next to established severity serum markers (CRP, fibrinogen, D-dimers).

Role of Cannabinoids in Oral Cancer.

Cannabinoids have incited scientific interest in different conditions, including malignancy, due to increased exposure to cannabis. Furthermore, cannabinoids are increasingly used to alleviate cancer-related symptoms. This review paper aims to clarify the recent findings on the relationship between cannabinoids and oral cancer, focusing on the molecular mechanisms that could link cannabinoids with oral cancer pathogenesis. In addition, we provide an overview of the current and future perspectives on the management of oral cancer patients using cannabinoid compounds. Epidemiological data on cannabis use and oral cancer development are conflicting. However, in vitro studies assessing the effects of cannabinoids on oral cancer cells have unveiled promising anti-cancer features, including apoptosis and inhibition of cell proliferation. Downregulation of various signaling pathways with anti-cancer effects has been identified in experimental models of oral cancer cells exposed to cannabinoids. Furthermore, in some countries, several synthetic or phytocannabinoids have been approved as medical adjuvants for the management of cancer patients undergoing chemoradiotherapy. Cannabinoids may improve overall well-being by relieving anxiety, depression, pain, and nausea. In conclusion, the link between cannabinoid compounds and oral cancer is complex, and further research is necessary to elucidate the potential risks or their protective impact on oral cancer.

Estrobolome and Hepatocellular Adenomas-Connecting the Dots of the Gut Microbial ß-Glucuronidase Pathway as a Metabolic Link.

Hepatocellular adenomas are benign endothelial tumors of the liver, mostly associated with female individual users of estrogen-containing medications. However, the precise factors underlying the selective development of hepatic adenomas in certain females remain elusive. Additionally, the conventional profile of individuals prone to hepatic adenoma is changing. Notably, male patients exhibit a higher risk of malignant progression of hepatocellular adenomas, and there are instances where hepatic adenomas have no identifiable cause. In this paper, we theorize the role of the human gastrointestinal microbiota, specifically, of bacterial species producing ß-glucuronidase enzymes, in the development of hepatic adenomas through the estrogen recycling pathway. Furthermore, we aim to address some of the existing gaps in our knowledge of pathophysiological pathways which are not yet subject to research or need to be studied further. As microbial ß-glucuronidases proteins recycle estrogen and facilitate the conversion of inactive estrogen into its active form, this process results in elevated levels of unbound plasmatic estrogen, leading to extended exposure to estrogen. We suggest that an imbalance in the estrobolome could contribute to sex hormone disease evolution and, consequently, to the advancement of hepatocellular adenomas, which are estrogen related.

Golgi Apparatus Target Proteins in Gastroenterological Cancers: A Comprehensive Review of GOLPH3 and GOLGA Proteins.

The Golgi apparatus plays a central role in protein sorting, modification and trafficking within cells; its dysregulation has been implicated in various cancers including those affecting the GI tract. This review highlights two Golgi target proteins, namely GOLPH3 and GOLGA proteins, from this apparatus as they relate to gastroenterological cancers. GOLPH3-a highly conserved protein of the trans-Golgi network-has become a key player in cancer biology. Abnormal expression of GOLPH3 has been detected in various gastrointestinal cancers including gastric, colorectal and pancreatic cancers. GOLPH3 promotes tumor cell proliferation, survival, migration and invasion via various mechanisms including activating the PI3K/Akt/mTOR signaling pathway as well as altering Golgi morphology and vesicular trafficking. GOLGA family proteins such as GOLGA1 (golgin-97) and GOLGA7 (golgin-84) have also been implicated in gastroenterological cancers. GOLGA1 plays an essential role in protein trafficking within the Golgi apparatus and has been associated with poor patient survival rates and increased invasiveness; GOLGA7 maintains Golgi structure while having been shown to affect protein glycosylation processes. GOLPH3 and GOLGA proteins play a pivotal role in gastroenterological cancer, helping researchers unlock molecular mechanisms and identify therapeutic targets. Their dysregulation affects various cellular processes including signal transduction, vesicular trafficking and protein glycosylation, all contributing to tumor aggressiveness and progression.

Association of Vitamin D Deficiency and Insufficiency with Pathology in Hospitalized Patients.

Vitamin D deficiency is one of the most common medical conditions, with approximately one billion people having low vitamin D levels. Vitamin D is associated with a pleiotropic effect (immunomodulatory, anti-inflammatory and antiviral), which can be essential for a better immune response. The aim of this research was to evaluate the prevalence of vitamin D deficiency/insufficiency in hospitalized patients focusing on demographic parameters as well as assessing the possibility of its associations with different comorbidities. Of 11,182 Romanian patients evaluated in the study over 2 years, 28.83% had vitamin D deficiency, 32.11% insufficiency and 39.05% had optimal vitamin D levels. The vitamin D deficiency was associated with cardiovascular disorders, malignancies, dysmetabolic disorders and SARS-CoV2 infection, older age and the male sex. Vitamin D deficiency was prevalent and showed pathology association, while insufficiency of vitamin D (20-30 ng/mL) had lower statistical relevance and represents a grey zone in vitamin D status. Guidelines and recommendations are necessary for homogeneity of the monitoring and management of inadequately vitamin D status in the risk categories.

Acute Esophageal Necrosis in Acute Pancreatitis-Report of a Case and Endoscopic and Clinical Perspective.

Esophageal stroke, also known as acute esophageal necrosis or Gurvits syndrome, is an entity that has gained more and more recognition in the last two decades. It is also named "black esophagus" because of striking black discoloration of the esophageal mucosa, with an abrupt transition to normal mucosa at the gastroesophageal junction. Its most common clinical presentation is represented by upper gastrointestinal bleeding and esophagogastroduodenoscopy is the main diagnostic tool. Among the etiopathogenetic and multiple predisposing factors described are hypovolemia, shock state, ischemia, congestive heart failure, acute renal failure, infections, trauma, and diabetes mellitus. Current management of this condition consists of treating the underlying pathology, nil per os, and antacid administration in uncomplicated cases. Although most of the cases have favorable prognosis, complications such as pneumomediastinum or esophageal stricture may occur and fatal cases are a consequence of underlying comorbidities.

Clinical characteristics and outcomes in carbohydrate antigen 19-9 negative pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of death from cancer worldwide. Tumor markers like carbohydrate antigen 19-9 (CA 19-9) have been proven valuable as a diagnostic tool and a predictor for tumor staging and response to therapy. AIM: To delineate the phenotype of normal CA 19-9 PDAC according to clinical features, disease staging and prognosis as compared with high CA 19-9 PDAC cases. METHODS: We performed a retrospective single-center analysis of all PDAC cases admitted in our Gastroenterology department over a period of 30 mo that were diagnosed by endoscopic ultrasound-guided tissue acquisition. Patients were divided into two groups according to CA 19-9 levels over a threshold of 37 U/mL. We performed a comparison between the two groups with regard to demographic and clinical data, biomarkers, tumor staging and 6-mo survival. RESULTS: Altogether 111 patients were recruited with 29 having documented normal CA 19-9 (< 37 U/mL). In the CA 19-9 negative group of patients, 20.68% had elevated levels of both CEA and CA 125, 13.79% for CA 125 only whilst 17.24% for CEA only. The two groups had similar demographic characteristics. Abdominal pain was more frequently reported in positive vs negative CA 19-9 PDAC cases (76.83% vs 55.17%), while smoking was slightly more prevalent in the latter group (28.04% vs 31.03%). Tumors over 2 cm were more frequently seen in the positive CA 19-9 group, reflecting a higher proportion of locally advanced and metastatic neoplasia (87.7% vs 79.3%). Six-month survival was higher for the negative CA 19-9 group (58.62% vs 47.56%). CONCLUSION: Elevated CA 19-9 at diagnosis seems to be associated with a more pronounced symptomatology, high tumor burden and poor prognosis compared to negative CA 19-9 PDAC cases. CEA and CA 125 can be adjunctive useful markers for PDAC, especially in CA 19-9 negative cases.

Risk of New-Onset Liver Injuries Due to COVID-19 in Preexisting Hepatic Conditions-Review of the Literature.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted the world and caused the 2019 coronavirus disease (COVID-19) pandemic. The clinical manifestations of the virus can vary from patient to patient, depending on their respective immune system and comorbidities. SARS-CoV-2 can affect patients through two mechanisms: directly by targeting specific receptors or by systemic mechanisms. We reviewed data in the latest literature in order to discuss and determine the risk of new-onset liver injuries due to COVID-19 in preexisting hepatic conditions. The particular expression of angiotensin-converting enzyme 2 (ACE2) receptors is an additional risk factor for patients with liver disease. COVID-19 causes more severe forms in patients with non-alcoholic fatty liver disease (NAFLD), increases the risk of cirrhosis decompensation, and doubles the mortality for these patients. The coinfection SARS-CoV-2-viral hepatitis B or C might have different outcomes depending on the stage of the liver disease. Furthermore, the immunosuppressant treatment administered for COVID-19 might reactivate the hepatic virus. The high affinity of SARS-CoV-2 spike proteins for cholangiocytes results in a particular type of secondary sclerosing cholangitis. The impact of COVID-19 infection on chronic liver disease patients is significant, especially in cirrhosis, influencing the prognosis and outcome of these patients.

An adult case with onset of celiac disease during chronic hepatitis C antiviral treatment.

We present the case of young women who developed celiac disease during the treatment for chronic hepatitis C. Celiac disease is now considered to be an immune disorder that is triggered by an environmental agent in genetically predisposed persons. Many studies have shown that the total prevalence of gluten sensitive-enteropathy has increased over last decades, and advances in serological screening leads to the idea that there are more celiac disease cases that are asymptomatic and undiagnosed. Actually, pegylated interferonum (IFN) in combination with ribavirine provides the most effective treatment for patient with chronic hepatitis C. However, interferon and ribavirin therapy are associated with induction or exacerbation of preexistent autoimmune disorders.

Histological and nonhistological criteria in the evaluation of liver involvement in chronic hepatitis C.

The treatment of chronic viral hepatitis is based mainly on interferon therapy. This therapy has many drawbacks, among which potentially dangerous side-effects. Moreover, the majority of the patients are asymptomatic at the time of diagnosis, and most of them will never develop cirrhosis, liver failure or hepatocellular carcinoma, making the decision to treat a difficult one. Currently, the best method of selection is liver biopsy, considered "the gold standard" for recommending antiviral treatment. The histological aspect can vary in different hepatic areas and the smaller the bioptic fragment, the more probable is the histopathologist's error in correctly defining the hepatitis. There has been made important progress in defining the degree of liver involvement using serological tests, with the purpose of avoiding liver biopsy, but this approach has not yet proven to be superior. At present, the benefits of the pretreatment liver biopsy outbalance the risks. The future developments in the domain of antiviral drugs or nonhistological tests for evaluating the liver injury (circulating cytokines, subtypes of collagen) will show if the liver biopsy could be abandoned.