A Hidden Cause of Hypertransaminasemia: Liver Toxicity Caused by Chelidonium Majus L. : Report of Two Cases of Herb-Induced Liver Injury and Literature Review.

BACKGROUND: In instances where individuals manifest elevated transaminase levels without a clearly discernible cause, a comprehensive patient history proves invaluable in unveiling latent triggers. In this report, we present 2 cases of herb-induced liver injury (HILI) characterized by severe hypertransaminasemia attributed to the consumption of Chelidonium majus L . (also known as greater celandine [GC]), an agent considered an alternative therapeutic remedy. AREAS OF UNCERTAINTY: Exploring the occurrence and range of clinical manifestations in HILI linked to Chelidonium majus L ., while also investigating the potential triggers and predisposing factors for hepatotoxic reactions post Chelidonium majus L. usage, remains challenging due to the absence of definitive laboratory tests to identify the causative agent. DATA SOURCES: Two case reports were detailed, and a systematic literature review using PubMed was conducted including published literature till March 2023. Moreover, a manual search of reference lists of pertinent articles was performed to identify any additional relevant missed publications. RESULTS: In the first case, a 64-year-old woman presented with jaundice, revealing a 1-month history of using GC capsules to manage gallstones. Diagnostic assessment identified HILI, gallstones, and choledocolithiasis, with transaminase levels exceeding 1000 IU/L. After discontinuing GC and receiving intravenous therapy with amino acids and phospholipids, the patient's condition significantly improved. Subsequently, she underwent endoscopic common bile duct stone removal and cholecystectomy. In the second case, a 66-year-old woman presented with elevated liver function test results discovered incidentally during musculoskeletal pain evaluation. Upon further questioning, the patient disclosed regular consumption of GC tea for "health promotion." Following intravenous therapy using amino acids and phospholipids, her transaminase levels returned to normal. The literature review identified 38 cases of HILI associated with GC preparations, primarily in adult women aged 27-77 years, with a predominant reporting location in Germany. Various forms of GC were used, with treatment durations ranging from 1 week to a year. Discontinuation of GC generally led to recovery in these cases. CONCLUSION: Chelidonium majus L ., a potent herb often used in alternative medicine, has significant hepatotoxic potential, requiring physicians to be vigilant in cases of unexplained liver injury.

Label-free electrochemical aptasensor for the detection of HepG2 hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common liver malignancy and is characterized by increasing incidence and high mortality rates. Current methods for the screening and diagnosis of HCC exhibit inherent limitations, highlighting the ever-growing need for the development of new methods for the early diagnosis of HCC. The aim of this work was to develop a novel electrochemical aptasensor for the detection of HepG2 cells, a type of circulating tumor cells that can be used as biomarkers for the early detection of HCC. A carbon screen-printed electrode was functionalized with a composite suspension containing graphene oxide, chitosan, and polyaniline nanoparticles to increase the electrode surface and provide anchoring sites for the HepG2 cell-specific aptamer. The aptamer was immobilized on the surface of the functionalized electrode using multipulse amperometry, an innovative technique that significantly reduces the time required for aptamer immobilization. The innovative platform was successfully employed for the first time for the amplification-free detection of HepG2 cells in a linear range from 10 to 200,000 cells/mL, with a limit of detection of 10 cells/mL. The platform demonstrated high selectivity and stability and was successfully used for the detection of HepG2 cells in spiked human serum samples with excellent recoveries.

Metabolic Signatures: Pioneering the Frontier of Rectal Cancer Diagnosis and Response to Neoadjuvant Treatment with Biomarkers-A Systematic Review.

Colorectal cancer (CRC) is one of the most aggressive, heterogenous, and fatal types of human cancer for which screening, and more effective therapeutic drugs are urgently needed. Early-stage detection and treatment greatly improve the 5-year survival rate. In the era of targeted therapies for all types of cancer, a complete metabolomic profile is mandatory before neoadjuvant therapy to assign the correct drugs and check the response to the treatment given. The aim of this study is to discover specific metabolic biomarkers or a sequence of metabolomic indicators that possess precise diagnostic capabilities in predicting the efficacy of neoadjuvant therapy. After searching the keywords, a total of 108 articles were identified during a timeframe of 10 years (2013-2023). Within this set, one article was excluded due to the use of non-English language. Six scientific papers were qualified for this investigation after eliminating all duplicates, publications not referring to the subject matter, open access restriction papers, and those not applicable to humans. Biomolecular analysis found a correlation between metabolomic analysis of colorectal cancer samples and poor progression-free survival rates. Biomarkers are instrumental in predicting a patient's response to specific treatments, guiding the selection of targeted therapies, and indicating resistance to certain drugs.

PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for patients with intrahepatic cholangiocarcinoma.

Cholangiocarcinoma, the second most common liver malignancy, after hepatocarcinoma is highly aggressive and usually diagnosed in advanced cases. In the era of personalized medicine, targeted therapy protocols are limited for cholangiocarcinoma and the only potential curative treatment, surgical resection, is seldom applicable.This retrospective study included all cases with pathology-confirmed intrahepatic cholangiocarcinoma admitted in a tertiary healthcare facility during a 10-year timeframe. Clinical information, laboratory values, imaging studies, and survival data were retrieved, and PD-L1 immunostaining was performed on representative pathology slides, for each case. From the total of 136 included cases (49 surgical resections and 87 liver biopsies), 38.97% showed PD-L1 positivity on tumoral cells, 34.8% on tumor infiltrating immune cells, 10.11% on epithelial cells within the peritumoral area and 15.95% on immune cells from the peritumoral area. Overall survival was significantly higher in the first two scenarios. However, after adjusting for age, tumor number, tumor size, and tumor differentiation in a multivariate analysis, only PD-L1 positivity on tumor infiltrating immune cells remained a favorable prognostic for survival. High immune cell counts also correlated with increased overall survival.Our study demonstrated that PD-1/PD-L1 checkpoint pathway in the microenvironment of intrahepatic cholangiocarcinoma bears prognostic significance. PD-L1 expression on immune cells, in both resection and biopsy specimens, might be a strong independent predictor for a favorable outcome.

Residents Can Do It! A Training Program in Laparoscopic Liver Surgery for General Surgery Residents.

INTRODUCTION: Laparoscopic liver resections (LLRs) constitute an area of surgery that has been kept away from residents in their hands-on training. The aim of our study is to assess the feasibility and the value of a didactic "step-by-step" program for LLR performed by residents using the swine training model. METHODS: From May 2018 to November 2019, three hands-on workshops were held. The protocol involved the performance of cholecystectomy, liver mobilization, minor and major hepatectomies. The participants' performance results in terms of operative time, blood loss, conversion, trainers' intervention, and intraoperative mortality, were recorded. The first workshop was comprised of 30 residents who previously participated in laparoscopic surgery workshops. In the second workshop, after six residents dropped out due to residency completion, the findings for the remaining 24 residents were compared to those for 24 junior-attending surgeons who did not follow the protocol and had not performed LLR previously, and to another 24 residents in a third workshop, who had not taken the training program before but followed the protocol. RESULTS: All residents fully completed the surgical procedures. Trained residents achieved better operative times and less blood loss compared to junior-attending surgeons (p < 0.017), however, the remaining parameters were comparable. When compared to non-trained residents, those who underwent training achieved significantly better results only in operative times (p < 0.001). CONCLUSION: A continuous LLR "step-by-step" training program on swine for residents is feasible and the "step-by-step" protocol is a valuable tool for a proper surgical education.

Integration of Virtual Reality in the Control System of an Innovative Medical Robot for Single-Incision Laparoscopic Surgery.

In recent years, there has been an expansion in the development of simulators that use virtual reality (VR) as a learning tool. In surgery where robots are used, VR serves as a revolutionary technology to help medical doctors train in using these robotic systems and accumulate knowledge without risk. This article presents a study in which VR is used to create a simulator designed for robotically assisted single-uniport surgery. The control of the surgical robotic system is achieved using voice commands for laparoscopic camera positioning and via a user interface developed using the Visual Studio program that connects a wristband equipped with sensors attached to the user's hand for the manipulation of the active instruments. The software consists of the user interface and the VR application via the TCP/IP communication protocol. To study the evolution of the performance of this virtual system, 15 people were involved in the experimental evaluation of the VR simulator built for the robotic surgical system, having to complete a medically relevant task. The experimental data validated the initial solution, which will be further developed.

The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver pathology worldwide. Meanwhile, liver cancer represents the sixth most common malignancy, with hepatocellular carcinoma (HCC) as the primary, most prevalent subtype. Due to the rising incidence of metabolic disorders, NAFLD has become one of the main contributing factors to HCC development. However, although NAFLD might account for about a fourth of HCC cases, there is currently a significant gap in HCC surveillance protocols regarding noncirrhotic NAFLD patients, so the majority of NAFLD-related HCC cases were diagnosed in late stages when survival chances are minimal. However, in the past decade, the focus in cancer genomics has shifted towards the noncoding part of the genome, especially on the microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which have proved to be involved in the regulation of several malignant processes. This review aims to summarize the current knowledge regarding some of the main dysregulated, noncoding RNAs (ncRNAs) and their implications for NAFLD and HCC development. A central focus of the review is on miRNA and lncRNAs that can influence the progression of NAFLD towards HCC and how they can be used as potential screening tools and future therapeutic targets.

Contrast-enhanced harmonic versus standard endoscopic ultrasound-guided fine-needle aspiration in solid pancreatic lesions: a single-center prospective randomized trial.

BACKGROUND: Contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) can visualize necrotic areas and vessels inside lesions. CH-EUS findings combined with EUS-guided fine-needle aspiration (EUS-FNA) improves diagnosis in pancreatic solid masses. CH-EUS can also guide EUS-FNA (CH-EUS-FNA), potentially improving the diagnostic rate of EUS-FNA, but such superiority has not been proved in prospective studies. We aimed to assess whether CH-EUS-FNA is superior to standard EUS-FNA for specific diagnosis of solid pancreatic masses and what factors affect the diagnostic rate. METHODS: This randomized controlled study in one tertiary medical academic center included patients with suspected pancreatic solid masses on transabdominal ultrasound or computed tomography (CT) scan. Two passes with a 22-G standard FNA needle were done using EUS-FNA and CH-EUS-FNA in random order, and the visible core obtained was sent for histological analysis. Final diagnosis was based on EUS-FNA or surgical specimen results and on 12-month follow-up by imaging. RESULTS: 148 patients were evaluated. EUS-FNA and CH-EUS-FNA showed diagnostic sensitivities of 85.5 % and 87.6 %, respectively (not significantly different) and the combined sensitivity of the two passes was 93.8 %. The false-negative rate was not significantly different when hypoenhanced or hyperenhanced lesions were compared with the EUS-FNA results. No differences were seen for the results related to location, size, tumor stage, chronic pancreatitis features, or presence of biliary plastic stent. CONCLUSIONS: The diagnostic rates for samples obtained using 22-G needles with standard EUS-FNA and CH-EUS-FNA were not statistically significantly different.

Ileocecal Obstruction Due to B-cell Non-Hodgkin Lymphoma.

We report a rare case of non-Hodgkin lymphoma presented as an ileocecal mass. The patient was a 77-year-old man with history of symptoms of partial bowel obstruction, intermittent right iliac fossa pain, loss of weight, vomiting and fatigue. Clinical signs included moderate abdominal tenderness with a palpable mass in the right iliac fossa at the physical examination. Colonoscopy revealed an intussusception of the right colon causing a complete stenosis. The patient developed complete bowel obstruction during hospitalization that required emergent surgical intervention. Intraoperatively an ileocecal mass was found measuring 10-12 cm in diameter, causing complete stenosis at its level and bowel dilatation proximally. Multiple nodules were found in the liver and the parietal peritoneum as well. An ileotransverso-anastomosis was performed and biopsies of the nodules were taken. Pathological evaluation revealed a diffuse large B cell non-Hodgkin'™s lymphoma of the ileocecum and the parietal peritoneum.

HER2 Overexpression in Periampullary Tumors According to Anatomical and Histological Classification-A Systematic Review.

Pancreatic cancer is one of the most aggressive, heterogeneous, and fatal types of human cancer; therefore, more effective therapeutic drugs are urgently needed. Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been identified as a cornerstone in this pathology. The aim of this review is to identify HER2 membrane overexpression in relation to pancreatic cancer pathways that can be used in order to develop a targeted therapy. After searching the keywords, 174 articles were found during a time span of 10 years, between 2013 and 2023, but only twelve scientific papers were qualified for this investigation. The new era of biomolecular research found a significant relationship between HER2 overexpression and pancreatic cancer cells in 25-30% of cases. The variables are dependent on tumor-derived cells, with differences in receptor overexpression between PDAC (pancreatic ductal adenocarcinoma), BTC (biliary tract cancer), ampullary carcinoma, and PNETs (pancreatic neuroendocrine tumors). HER2 overexpression is frequently encountered in human pancreatic carcinoma cell lines, and the ERBB family is one of the targets in the near future of therapy, with good results in phase I, II, and III studies evaluating downregulation and tumor downstaging, respectively.

Evaluation of miR-148a-3p and miR-106a-5p as Biomarkers for Prostate Cancer: Pilot Study.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that may function as tumor suppressors or oncogenes. Alteration of their expression levels has been linked to a range of human malignancies, including cancer. The objective of this investigation is to assess the relative expression levels of certain miRNAs to distinguish between prostate cancer (PCa) from benign prostatic hyperplasia (BPH). Blood plasma was collected from 66 patients diagnosed with BPH and 58 patients with PCa. Real-time PCR technology was used to evaluate the relative expression among the two groups for miR-106a-5p and miR-148a-3p. The significant downregulation of both miRNAs in plasma from PCa versus BPH patients suggests their potential utility as diagnostic biomarkers for distinguishing between these conditions. The concurrent utilization of these two miRNAs slightly enhanced the sensitivity for discrimination among the two analyzed groups, as shown in ROC curve analysis. Further validation of these miRNAs in larger patient cohorts and across different stages of PCa may strengthen their candidacy as clinically relevant biomarkers for diagnosis and prognosis.

Gelatin-Based Liver Phantoms for Training Purposes: A Cookbook Approach.

Background: Patients with liver pathology benefit from image-guided interventions. Training for interventional procedures is recommended to be performed on liver phantoms until a basic proficiency is reached. In the last 40 years, several attempts have been made to develop materials to mimic the imaging characteristics of the human liver in order to create liver phantoms. There is still a lack of accessible, reproducible and cost-effective soft liver phantoms for image-guided procedure training. Methods: Starting from a CT-scan DICOM file, we created a 3D-printed liver mold using InVesalius (Centro de Tecnologia da informação Renato Archer CTI, InVesalius 3 open-source software, Campinas, Brazil) for segmentation, Autodesk Fusion 360 with Netfabb (Autodesk software company, Fusion 360 2.0.19426 with Autodesk Netfabb Premium 2023.0 64-Bit Edition, San Francisco, CA, USA) for 3D modeling and Stratasys Fortus 380 mc 3D printer (Stratasys 3D printing company, Fortus 380 mc 3D printer, Minneapolis, MN, USA). Using the 3D-printed mold, we created 14 gelatin-based liver phantoms with 14 different recipes, using water, cast sugar and dehydrated gelatin, 32% fat bovine milk cream with intravenous lipid solution and technical alcohol in different amounts. We tested all these phantoms as well as ex vivo pig liver and human normal, fatty and cirrhotic liver by measuring the elasticity, shear wave speed, ultrasound attenuation, CT-scan density, MRI signal intensity and fracture force. We assessed the results of the testing performed, as well as the optical appearance on ultrasound, CT and MRI, in order to find the best recipe for gelatin-based phantoms for image-guided procedure training. Results: After the assessment of all phantom recipes, we selected as the best recipe for transparent phantoms one with 14 g of gelatin/100 mL water and for opaque phantom, the recipes with 25% cream. Conclusions: These liver gelatin-based phantom recipes are an inexpensive, reproducible and accessible alternative for training in image-guided and diagnostic procedures and will meet most requirements for valuable training.

Prognostic Indicators of Overall Survival in Hepatocellular Carcinoma Patients Undergoing Liver Resection.

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and the third contributor to malignancy-related deaths worldwide. The hepatic venous pressure gradient (HVPG), transient elastography-liver stiffness measurement (TE-LSM), and the association between TBS (tumor burden score), alpha-fetoprotein levels, and the Child-Pugh classification (TAC score) can serve as valuable prognostic indicators for these patients. Therefore, the main objective of our research was to analyze the prognostic value of the HVPG, TE-LSM, TBS, and TAC scores. An observational and survival study was conducted on 144 subjects. Our findings indicated that HVPG greater than 10 mmHg, AFP surpassing 400 ng/mL, an advanced C-P class, and low TAC score are independent predictors of overall survival. During the multivariate analysis, AFP serum levels and C-P class proved statistically significant. The present study revealed significant differences in overall survival between the two groups divided upon HVPG values and settled by the cutoff of 10 mmHg (p = 0.02). Moreover, by dividing the cohort into three groups based on the TAC score (very low, low, and moderate), statistically significant differences in overall survival were observed across the groups (p = 0.004).

The Staging of Newly Diagnosed Hepatocellular Carcinoma in Romania. A National Multicentric Study.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a significant public health issue, with an increasing incidence and prevalence and a high incidence-to-mortality ratio. The prognosis of HCC depends on two competing factors, tumor burden and underlying liver disease severity, encompassed in the Barcelona Clinic Liver Cancer (BCLC) classification. To assess HCC staging and the way staging affects eligibility for treatment at the time of the first diagnosis in Romania in the setting of opportunistic diagnosis, in the absence of a national HCC screening policy. METHODS: Data regarding HCC staging, underlying liver disease, and eligibility for treatment at the time of diagnosis was analyzed using a prospectively maintained multicentric database, which included patients from the five largest tertiary care hepatology units in the country between June 2016 and February 2020. RESULTS: A consecutive series of 477 patients was included. The distribution within BCLC classes was as follows: very early (0) 7.1%, early (A) 34.3%, intermediate (B) 19.4%, advanced (C) 14.2%, terminal (D) 24.7%. At the time of the diagnosis, 198 (41.5%) were eligible for a curative intent treatment, while 359 (75.2%) were eligible for a disease-modifying therapy. 228 patients (47.8%) had decompensated liver disease at the time of diagnosis, the most common decompensating event being ascites (78.1%). CONCLUSIONS: A large proportion of HCC cases are diagnosed at the time of a decompensating event, severely restricting the therapeutic potential. Proactive diagnostic strategies should be implemented to improve the rate of actionable diagnosis.

Emergency liver resection for non-traumatic lesions. A systematic review.

AIM: Primary liver tumors have an incidence of 20% regarding benign tumors respectively 5.7% of the overall incident cases of cancer. In any major hepatic injury, the surgical treatment has two main goals: hemostasis and excision of the affected liver segments. We aimed to systematic review the non-traumatic emergency liver resections, in order to raise concern about a rather rare, but difficult to treat hepatic pathology, which implies divergent therapeutical approach, and emergency liver surgery remains the first or backup option. METHODS: A literature survey was performed guided by the words "liver resections", "major liver resections", "emergency liver resection". "hepatocellular carcinoma" using four databases: Pubmed, Scopus, Web of Science and Embase. All titles referred in English, published from 2000 until 2021, were checked for eligibility. RESULTS: Six publications were considered relevant for major liver resections in emergency, from a total of 331 articles that were reviewed. Large hepatocellular carcinomas and adenomas were the most common types of tumors found at risk for spontaneous rupture. The patients with hemodynamic instability, reduced liver function and large tumors had lower long-term survival and disease-free survival. Major hepatectomy was indicated as a viable solution for prolonging survival rate, whenever the patient's general status permits it per primam. CONCLUSIONS: Emergency major liver resection for tumoral causes prolongs survival even if the cause is usually malignant. The tumor can be resected with negative resection margins, respecting the correct oncological requirements, both per primam or staged approach according to each case specifically. KEY WORDS: Adenoma, Emergency, Hemorrhage, Hepatocellular Carcinoma, Liver Resection, Liver Tumors.

Safety Issues in the Development of an Innovative Medical Parallel Robot Used in Renal Single-Incision Laparoscopic Surgery.

Robotic-assisted single-incision laparoscopic surgery (SILS) is becoming an increasingly widespread field worldwide due to the benefits it brings to both the patient and the surgeon. The goal of this study is to develop a secure robotic solution for SILS, focusing specifically on urology, by identifying and addressing various safety concerns from an early design stage. Starting with the medical tasks and protocols, the technical specifications of the robotic system as well as potential; hazards have been identified. By employing competitive engineering design methods such as Analytic Hierarchy Process (AHP), Risk assessment, and Failure Mode and Effects Analysis (FMEA), a safe design solution is proposed. A set of experiments is conducted to validate the proposed concept, and the results strongly support the development of the experimental model. The Finite Element Analysis (FEA) method is applied to validate the mechanical architecture within a set of simulations, demonstrating the compliance of the robotic system with the proposed technical specifications and its capability to safely perform SILS procedures.

Overlap syndrome of autoimmune hepatitis and primary biliary cholangitis complicated with atypical hepatocellular carcinoma: a case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary tumor of the liver. The majority of HCCs are associated most frequently with chronic B or C viral hepatitis, alcohol intake or aflatoxin exposure. Cirrhosis is a strong risk factor associated with HCC. The causes of liver cirrhosis are chronic viral hepatitis, alcohol intake, metabolic diseases (NAFLD), hemocromathosis, alfa 1 antitrypsisn deficiency. All aetiologic forms of cirrhosis are at risk to be complicated by HCC development, but the risk is higher for patients diagnosed with chronic viral hepatitis. Comparing to the above-mentioned causes, PBC and AIH are less associated with the risk of HCC development. A 71-year old Caucasian female previously diagnosed with overlap syndrome (AIH type 1 and PBC-ANA, SMA and AMA antibodies positive), liver cirrhosis, a nodule in the VI/VIIth hepatic segment, systemic sclerosis sine scleroderma, Hashimoto's thyroiditis, antiphospholipid syndrome, gastric antral vascular ectasia (GAVE) (with 2 previous sessions of argon plasma coagulation), cholecystectomy, arterial hypertension and nephro-angiosclerosis presented to the 2nd Department of Internal Medicine in Cluj-Napoca for a follow-up. The patient was following treatment with UDCA (Ursodeoxycholic acid), azathioprine, Plaquenil, calcium channel blockers, angiotensin-converting-enzyme inhibitor, calcium and vitamin D supplementation. The abdominal ultrasound showed a subcapsular hypoechoic nodule with a diameter of 29 mm (at the moment of the diagnosis the diameter was 9/10 mm) in the VI/VIIth hepatic segment. The contrast-enhanced ultrasound (CEUS) characterised the nodule as specific for hepatocellular carcinoma (LI-RADS 5). On MRI with gadoxetate disodium the nodule was hypovascular, non-specific, being classified as LI-RADS 3. An atypical resection of the VIIth hepatic segment was performed and the histohistological examination and imunohistochemistry (Hep Par-a positive, Glypican3 positive, CD34 positive) revealed a moderately differentiated hepatocellular carcinoma (G2), pT2 N0 M0 L0 V1 R0. CONCLUSION: Autoimmune hepatitis, PBC and the overlap syndrome are less associated with the development of liver cirrhosis and HCC than other chronic liver diseases, especially if other risk factors are not associated. This case highlights the importance of a proper surveillance of cirrhotic patients every 6 months including abdominal ultrasound and AFP levels is crucial for an early diagnosis of a HCC.

Distinct Morphological and Molecular Profiles of NAFLD and NAFLD-associated HCC Revealed by Immunohistochemistry and MicroRNA Analysis.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a common hepatic condition that can progress to hepatocellular carcinoma (HCC) in non-cirrhotic livers. To better understand the development of NAFLD-associated HCC, we performed an integrated morphological and molecular analysis to identify new insights that can improve the follow-up of NAFLD patients. METHODS: Our study included a cohort of 14 NAFLD-associated HCC and 41 NAFLD patients. We analyzed clinical parameters, a four-microRNA (miRNA) panel (miR-21-5p, miR-34a-5p, miR-130a-3p, and miR-155-3p) panel and their relationship with p53 and ß-catenin expression. RESULTS: In the study cohort, the NAFLD-associated HCC patients were predominantly male, older, had significantly altered hepatic function, and a higher incidence of hypertension, type 2 diabetes, and dyslipidemia. Morphologically, the NAFLD-HCC group had substantially higher steatosis, ballooning, and fibrosis grades than the NAFLD group. The ß-catenin expression was higher in both adjacent non-tumoral liver tissue (ANT) from NAFLD-associated HCC patients and in HCC tissue com-pared with NAFLD samples. The 4 miRNAs panel showed a dysregulated expression profile between NAFLD, ANT and HCC samples. CONCLUSIONS: This study provides important insights regarding the molecular mechanisms underlying HCC progression in NAFLD patients, allowing for the development of better screening strategies for the early detection of NAFLD-associated HCC.

The Influence of Intravenous Lidocaine Infusion on Postoperative Outcome and Neutrophil-to-Lymphocyte Ratio in Colorectal Cancer Patients. A Pilot Study.

BACKGROUND AND AIMS: In the last years increasing scientific evidence drew attention on the potential effects of anesthetic drugs on postoperative outcome in cancer patients. Local anesthetics, especially lidocaine, have been intensively studied in relation with postoperative outcome in colorectal cancer patients. Our study objectives were to investigate the effects of perioperative intravenous lidocaine infusion on neutrophil-to-lymphocyte ratio and short-term postoperative outcome. Additionally, we also looked at 1 year outcome after intended radical colorectal cancer surgery. METHODS: 150 patients scheduled for colorectal cancer surgery were randomized to receive sevoflurane anaesthesia with or without 48 hours lidocaine infusion. RESULTS: 73 patients were included in the group A (sevoflurane) and 77 in the group B (sevoflurane with lidocaine). Lidocaine infusion did not modify neutrophil-to-lymphocyte ratio at 24 hours after surgery (p=0.58). Patients receiving intravenous lidocaine had significantly lower morphine consumption (p=0.04), faster mobilization time (p=0.001) and fewer days spent in the hospital (p=0.04). Moreover, at 1 year follow- up, patients in group B had a significant decreased rate of recurrences (p=0.03). There was no significant difference in 1 year survival (p=0.22). CONCLUSIONS: In our study, intravenous lidocaine infusion hastened the postoperative recovery of patients in terms of mobilization, hospital discharge and opioid consumption and reduced 1 year recurrence rate. Further studies on larger groups of patients are needed.