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.

Novel Insights into Postoperative Surveillance in Resected Pancreatic Cystic Neoplasms-A Review.

Pancreatic cystic lesions (PCL) are frequently encountered in clinical practice and some are referred to surgery due to their neoplastic risk or malignant transformation. The management of PCL involves complex decision-making, with postoperative surveillance being a key component for long-term outcomes, due to the potential for recurrence and postoperative morbidity. Unfortunately, the follow-up of resected patients is far from being optimal and there is a lack of consensus on recommendations with regard to timing and methods of surveillance. Here, we summarize the current knowledge on the postoperative surveillance of neoplastic pancreatic cysts, focusing on the mechanisms and risk factors for recurrence, the recurrence rates according to the initial indication for surgery, the final result of the surgical specimen and neoplastic risk in the remaining pancreas, as well as the postsurgical morbidity comprising pancreatic exocrine insufficiency, metabolic dysfunction and diabetes after resection, according to the type of surgery performed. We analyze postsurgical recurrence rates and morbidity profiles, as influenced by different surgical techniques, to better delineate at-risk patients, and highlight the need for tailored surveillance strategies adapted to preoperative and operative factors with an impact on outcomes.

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.

Introducing Colorectal Cancer Screening in Romania - Preliminary Results from the Regional Pilot Programs (ROCCAS).

BACKGROUND AND AIMS: Colorectal cancer (CRC) is the third cause of cancer-related death worldwide. Screening programs can reduce CRC mortality rates by up to 60%. In line with the European Union recommendations, Romania started the first four regional pilot screening programs in 2020 (the ROCCAS II projects). This study reports the interim screening performance indicators. METHODS: People aged 50 to 74 years were invited to the screening program. General practitioners (GPs) evaluated CRC risk based on a survey. High-risk or symptomatic individuals were referred directly to colonoscopy. The average risk participants received a fecal immunochemical test (FIT). Positive cases were invited to colonoscopy. Three regions were screened using the OC-SENSOR® (South-Muntenia, Bucharest-Ilfov, South-East) and one region (South-West) used the FOB GOLD®. The data was collected in the ROCCAS screening electronic registry. The following FIT parameters were evaluated: rates of return, invalidity, positivity, and colonoscopy acceptance rate according to age group, gender, region of provenience, and vulnerability status. RESULTS: We included all cases screened between January 1, 2022 and September 30, 2023. In total, 168,958 people received the FIT test within the projects. The global FIT return rate was 90%. Factors associated with a higher return rate were female gender (90.77% vs 88.83%, p<0.0001), vulnerable status (91.23% vs 88.83%; p<0.00001), and rural residence (91.84% vs 88.42%, p<0.00001). The overall positivity rate was 5.75%. It was higher in males (7.64% vs 4.57% in females, p<0.00001) and progressively increased with the age group. The total invalid FIT rate was 5.87%, significantly lower for OC-SENSOR® (2.24%) than for the FOB GOLD® (13.6%). The overall acceptability rate for colonoscopy was 51.3%. CONCLUSIONS: According to our preliminary data, GP's participation in the pilot programs ensured adequate adherence to screening through FIT. The rate for FIT return and positivity were acceptable for both tests, while the invalid rate was much higher in FOB GOLD® compared to the OC-SENSOR®. Moreover, colonoscopy acceptance needs to be improved. Our preliminary analysis revealed the screening performance indicators meet the EU recommendations and fulfill the premises for national-level expansion of the program starting in 2024.

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).

The Role of KRAS Mutation in Colorectal Cancer-Associated Thrombosis.

Venous thromboembolic events (VTE) are common in patients with colorectal cancer (CRC) and represent a significant contributor to morbidity and mortality. Risk stratification is paramount in deciding the initiation of thromboprophylaxis and is calculated using scores that include tumor location, laboratory values, patient clinical characteristics, and tumor burden. Commonly used risk scores do not include the presence of molecular aberrations as a variable. This retrospective study aims to confirm the link between KRAS-activating mutations and the development of VTE in CRC. A total of 166 patients were included in this study. They were split into two cohorts based on KRAS mutational status. We evaluated the frequency and mean time to VTE development stratified by the presence of KRAS mutations. Patients with mutant KRAS had an odds ratio (OR) of 2.758 for VTE compared to KRAS wild-type patients, with an increased risk of thrombosis being maintained in KRAS mutant patients even after adjusting for other known VTE risk factors. Taking into account the results of this study, KRAS mutation represents an independent risk factor for VTE.

Safety, Efficacy and Persistence of Advanced Therapies in Inflammatory Bowel Disease: Results from ORIGINS. A Retrospective Observational Study.

BACKGROUND AND AIMS: Real-world assessments of efficacy and safety of advanced therapies used for inflammatory bowel disease (IBD) patients are limited. We aimed to report safety, efficacy and treatment persistence of new molecules (infliximab, adalimumab, vedolizumab, tofacitinib, ustekinumab) in a retrospective multicentric national Romanian analysis. METHODS: We conducted a nationwide, retrospective observational multicentric study. Data were collected retrospectively from electronic and paper files. Patients who started on one of the five investigated molecules during December 2019-December 2021 were included. The main outcome measures were clinical remission, endoscopic healing, persistence on treatment and safety data. RESULTS: A total of 678 adult patients from 24 Romanian IBD centers with a diagnosis of ulcerative colitis or Crohn's disease were included. Participants had previously failure to one (268, 39.5%), two (108, 15%) or more treatment lines and only 38% (259) were biologic naïve. In the 24 months study period, most patients were started on vedolizumab (192, 28%), followed by adalimumab, infliximab, ustekinumab and tofacitinib. In biologic-naïve patients, most physicians (72%) preferred anti-TNF treatment as first line biologic (93 patients started on infliximab, 92 on adalimumab), followed by vedolizumab, ustekinumab and tofacitinib. During follow-up, 71% (470, p=0.05) of patients achieved clinical remission and 36% (134, p=0.03) achieved mucosal healing. The 6 months milestone for persistence was reached in 78% (530) of cases. Almost half of patients (47%, 316 patients) persisted on their current treatment for over 12 months. Overall, an adverse reaction was reported for 67 (10.4%) patients, with no lethal events. CONCLUSIONS: Population of biologic-experienced IBD patients in Romania is increasing and is becoming more difficult to achieve long-term disease control. Discontinuation rates for advanced therapies are high.

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.

Computer-Based Diagnosis of Celiac Disease by Quantitative Processing of Duodenal Endoscopy Images.

Celiac disease (CD) is a lifelong chronic autoimmune systemic disease that primarily affects the small bowel of genetically susceptible individuals. The diagnostics of adult CD currently rely on specific serology and the histological assessment of duodenal mucosa on samples taken by upper digestive endoscopy. Because of several pitfalls associated with duodenal biopsy sampling and histopathology, and considering the pediatric no-biopsy diagnostic criteria, a biopsy-avoiding strategy has been proposed for adult CD diagnosis also. Several endoscopic changes have been reported in the duodenum of CD patients, as markers of villous atrophy (VA), with good correlation with serology. In this setting, an opportunity lies in the automated detection of these endoscopic markers, during routine endoscopy examinations, as potential case-finding of unsuspected CD. We collected duodenal endoscopy images from 18 CD newly diagnosed CD patients and 16 non-CD controls and applied machine learning (ML) and deep learning (DL) algorithms on image patches for the detection of VA. Using histology as standard, high diagnostic accuracy was seen for all algorithms tested, with the layered convolutional neural network (CNN) having the best performance, with 99.67% sensitivity and 98.07% positive predictive value. In this pilot study, we provide an accurate algorithm for automated detection of mucosal changes associated with VA in CD patients, compared to normally appearing non-atrophic mucosa in non-CD controls, using histology as a reference.

Serum anti-tissue transglutaminase IgA and prediction of duodenal villous atrophy in adults with suspected coeliac disease without IgA deficiency (Bi.A.CeD): a multicentre, prospective cohort study.

BACKGROUND: Whether coeliac disease in adults can be diagnosed with serology alone remains controversial. We aimed to evaluate the accuracy of serum anti-tissue transglutaminase IgA (tTG-IgA) in the diagnosis of coeliac disease. METHODS: In this multicentre, prospective cohort study, adult participants (aged ≥18 years) with suspected coeliac disease without IgA deficiency who were not on a gluten-free diet and who had a local serum tTG-IgA measurement, were enrolled from Feb 27, 2018, to Dec 24, 2020, by 14 tertiary referral centres (ten from Europe, two from Asia, one from Oceania, and one from South America) to undergo local endoscopic duodenal biopsy. Local serum tTG-IgA was measured with 14 different test brands and concentration expressed as a multiple of each test's upper limit of normal (ULN), and defined as positive when greater than 1 times the ULN. The main study outcome was the reliability of serum tests for the diagnosis of coeliac disease, as defined by duodenal villous atrophy (Marsh type 3 or Corazza-Villanacci grade B). Histology was evaluated by the local pathologist, with discordant cases (positive tTG-IgA without duodenal villous atrophy or negative tTG-IgA with duodenal villous atrophy) re-evaluated by a central pathologist. The reliability of serum tests for the prediction of duodenal villous atrophy was evaluated according to sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) for categorical and continuous data. FINDINGS: We enrolled 436 participants with complete local data on serum tTG-IgA and duodenal histology (296 [68%] women and 140 [32%] men; mean age 40 years [SD 15]). Positive serum tTG-IgA was detected in 363 (83%) participants and negative serum tTG-IgA in 73 (17%). Of the 363 participants with positive serum tTG-IgA, 341 had positive histology (true positives) and 22 had negative histology (false positives) after local review. Of the 73 participants with negative serum tTG-IgA, seven had positive histology (false negatives) and 66 had negative histology (true negatives) after local review. The positive predictive value was 93·9% (95% CI 89·2-98·6), the negative predictive value was 90·4% (85·5-95·3), sensitivity was 98·0% (95·3-100·0), and specificity was 75·0% (66·6-83·4). After central re-evaluation of duodenal histology in 29 discordant cases, there were 348 true positive cases, 15 false positive cases, 66 true negative cases, and seven false negative cases, resulting in a positive predictive value of 95·9% (92·0-99·8), a negative predictive value of 90·4% (85·5-95·3), a sensitivity of 98·0% (95·3-100·0), and a specificity of 81·5% (73·9-89·1). Either using the local or central definition of duodenal histology, the positive predictive value of local serum tTG-IgA increased when the serological threshold was defined at increasing multiples of the ULN (p<0·0001). The AUC for serum tTG-IgA for the prediction of duodenal villous atrophy was 0·87 (95% CI 0·81-0·92) when applying the categorical definition of serum tTG-IgA (positive [>1 × ULN] vs negative [≤1 × ULN]), and 0·93 (0·89-0·96) when applying the numerical definition of serum tTG-IgA (multiples of the ULN). Additional endoscopic findings included peptic gastritis (nine patients), autoimmune atrophic gastritis (three), reflux oesophagitis (31), gastric or duodenal ulcer (three), and Barrett's oesophagus (one). In the 1-year follow-up, a midgut ileum lymphoma was diagnosed in a woman on a gluten-free diet. INTERPRETATION: Our data showed that biopsy could be reasonably avoided in the diagnosis of coeliac disease in adults with reliable suspicion of coeliac disease and high serum tTG-IgA. FUNDING: None.

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.

Metastatic Renal Cell Carcinoma to Pancreas: Case Series and Review of the Literature.

Metastasis to the pancreas represents a small proportion of all pancreatic malignancies. Among primary tumors that metastasize to the pancreas, renal cell carcinoma (RCC) is one of the most common causes of metastatic pancreatic lesions. We herein report a case series of three patients with pancreatic metastasis from RCC. The first is a 54-year-old male with a history of left nephrectomy for RCC, in whom an isthmic pancreatic mass suggestive of a neuroendocrine lesion was found during oncological follow-up. Endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) identified pancreatic metastasis of RCC and the patient was referred for surgery. The second case is a 61-year-old male, hypertensive, diabetic, with left nephrectomy for RCC six years previously, who complained of weight loss and was found with a hyperenhancing mass in the head of the pancreas and a lesion with a similar pattern in the gallbladder. EUS-FNB from the pancreas proved to be a metastatic pancreatic lesion. Cholecystectomy and treatment with tyrosine kinase inhibitors were recommended. The third case is a 68-year-old dialysis patient referred for evaluation of a pancreatic mass, also confirmed by EUS-FNB, who was started on sunitinib treatment. We report a literature summary on epidemiology and clinical features, diagnosis and differential diagnosis and treatment and outcomes in pancreatic metastasis of RCC.

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.

Oral Anticoagulation in Patients with Chronic Liver Disease.

The administration of an anticoagulant in patients with liver disease (nonalcoholic steatohepatitis-NASH, nonalcoholic fatty liver disease-NAFLD, chronic hepatitis, or cirrhosis) who have an indication (atrial fibrillation, venous thrombosis, or pulmonary embolism) is challenging because there is an imbalance between thrombosis and bleeding. There is a need to focus our attention on preventing risk factors because diabetes, obesity, dyslipidemia, smoking, and sedentary behavior are risk factors for both NASH/NAFLD and AF, and these patients require anticoagulant treatment. Patients with advanced liver disease (Child-Pugh C) were excluded from studies, so vitamin K antagonists (VKAs) are still recommended. Currently, VKAs are recommended for other conditions (antiphospholipid syndrome, mitral valve stenosis, and mechanical valve prosthesis). Amongst the patients under chronic anticoagulant treatment, especially for the elderly, bleeding as a result of the improper use of warfarin is one of the important causes of emergency admissions due to adverse reactions. DOACs are considered to be efficient and safe, with apixaban offering superior protection against stroke and a good safety profile as far as major bleeding is concerned compared to warfarin. DOACs are safe in the Child-Pugh A and B classes (except rivaroxaban), and in the Child-Pugh C class are contraindicated. Given that there are certain and reliable data for chronic kidney disease regarding the recommendations, in liver function impairment more randomized studies must be carried out, as the current data are still uncertain. In particular, DOACs have a simple administration, minimal medication interactions, a high safety and effectiveness profile, and now a reversal agent is available (for dabigatran and idarucizumab). Patients are also statistically more compliant and do not require INR monitoring.

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.

Links between Metabolic Syndrome and Hypertension: The Relationship with the Current Antidiabetic Drugs.

Hypertension poses a significant burden in the general population, being responsible for increasing cardiovascular morbidity and mortality, leading to adverse outcomes. Moreover, the association of hypertension with dyslipidaemia, obesity, and insulin resistance, also known as metabolic syndrome, further increases the overall cardiovascular risk of an individual. The complex pathophysiological overlap between the components of the metabolic syndrome may in part explain how novel antidiabetic drugs express pleiotropic effects. Taking into consideration that a significant proportion of patients do not achieve target blood pressure values or glucose levels, more efforts need to be undertaken to increase awareness among patients and physicians. Novel drugs, such as incretin-based therapies and renal glucose reuptake inhibitors, show promising results in decreasing cardiovascular events in patients with metabolic syndrome. The effects of sodium-glucose co-transporter-2 inhibitors are expressed at different levels, including renoprotection through glucosuria, natriuresis and decreased intraglomerular pressure, metabolic effects such as enhanced insulin sensitivity, cardiac protection through decreased myocardial oxidative stress and, to a lesser extent, decreased blood pressure values. These pleiotropic effects are also observed after treatment with glucagon-like peptide-1 receptor agonists, positively influencing the cardiovascular outcomes of patients with metabolic syndrome. The initial combination of the two classes may be the best choice in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors because of their complementary mechanisms of action. In addition, the novel mineralocorticoid receptor antagonists show significant cardio-renal benefits, as well as anti-inflammatory and anti-fibrotic effects. Overall, the key to better control of hypertension in patients with metabolic syndrome is to consider targeting multiple pathogenic mechanisms, using a combination of the different therapeutic agents, as well as drastic lifestyle changes. This article will briefly summarize the association of hypertension with metabolic syndrome, as well as take into account the influence of antidiabetic drugs on blood pressure control.

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.

Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects.

Although pancreatic cancer (PC) was considered in the past an orphan cancer type due to its low incidence, it may become in the future one of the leading causes of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of PC, being a highly aggressive malignancy and having a 5-year survival rate of less than 10%. Non-modifiable (family history, age, genetic susceptibility) and modifiable (smoking, alcohol, acute and chronic pancreatitis, diabetes mellitus, intestinal microbiota) risk factors are involved in PC pathogenesis. Chronic inflammation induced by various factors plays crucial roles in PC development from initiation to metastasis. In multiple malignant conditions such as PC, cytokines, chemokines, and growth factors activate the class I phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) (PI3K/AKT/mTOR) signaling pathway, which plays key roles in cell growth, survival, proliferation, metabolism, and motility. Currently, mTOR, AKT, and PI3K inhibitors are used in clinical studies. Moreover, PI3K/mTOR dual inhibitors are being tested in vitro and in vivo with promising results for PC patients. The main aim of this review is to present PC incidence, risk factors, tumor microenvironment development, and PI3K/AKT/mTOR dysregulation and inhibitors used in clinical, in vivo, and in vitro studies.

Pancreatic involvement in celiac disease.

Celiac disease (CD) is well recognized as a systemic, chronic autoimmune disease mainly characterized by gluten-sensitive enteropathy in genetically predisposed individuals but with various extraintestinal features. One of the affected organs in CD is the pancreas, consisting of both endocrine and exocrine alterations. Over the last decades there has been increasing interest in the pancreatic changes in CD, and this has been reflected by a great number of publications looking at this extraintestinal involvement during the course of CD. While pancreatic endocrine changes in CD, focusing on type 1 diabetes mellitus, are well documented in the literature, the relationship with the exocrine pancreas has been less studied. This review summarizes currently available evidence with regard to pancreatic exocrine alterations in CD, focusing on risk of pancreatitis in CD patients, association with autoimmune pancreatitis, prevalence and outcomes of pancreatic exocrine insufficiency in newly diagnosed and gluten-free diet treated CD patients, and the link with cystic fibrosis. In addition, we discuss mechanisms behind the associated pancreatic exocrine impairment in CD and highlight the recommendations for clinical practice.