Unveiling novel serum biomarkers in intrahepatic cholangiocarcinoma: a pilot proteomic exploration.

Recent advancements in proteomics have shown promise in identifying biomarkers for various cancers. Our study is the first to compare the serum proteomes of intrahepatic cholangiocarcinoma (iCCA) with cirrhosis (CIR), primary sclerosing cholangitis (PSC), and hepatocellular carcinoma (HCC), aiming to identify a proteomic signature that can effectively distinguish among these conditions. Utilizing high-throughput mass spectrometry on serum samples, we identified 845 proteins, of which 646 were suitable for further analysis. Unique clustering patterns were observed among the five groups, with significant proteomic differences. Our key findings include: S100 calcium-binding protein A9 (S100A9) and haptoglobin (HP) were more abundant in iCCA, while intercellular adhesion molecule 2 (ICAM2) was higher in HCC. Serum amyloid A1 (SAA1) and A4 (SAA4) emerged as potential biomarkers, with SAA1 significantly different in the iCCA vs healthy controls (HC) comparison, and SAA4 in the HCC vs HC comparison. Elevated levels of vascular cell adhesion molecule 1 (VCAM-1) in HCC suggested its potential as a differentiation and diagnostic marker. Angiopoietin-1 receptor (TEK) also showed discriminatory and diagnostic potential in HCC. ELISA validation corroborated mass spectrometry findings. Our study underscores the potential of proteomic profiling in distinguishing iCCA from other liver conditions and highlights the need for further validation to establish robust diagnostic biomarkers.

Long-term results of multimodal treatment of the prostate using the Thulium Laser.

Background and aims: To evaluate a novel multimodal treatment (TLP) that integrates the use of a thulium laser, bipolar transurethral resection of the prostate (TURP), and "button-type" bipolar plasma vaporization for the endoscopic treatment of benign prostatic hyperplasia (BPH). Methods: From March 2018 to December 2021, we prospectively evaluated 220 patients with symptomatic BPH who underwent TLP. Patients were assessed based on the International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), and postvoid residual urine (PVR). Perioperative and postoperative follow-up data were analyzed. Results: The mean age at surgery was 66.74 years (SD 8.21). The median prostate size was 80 (IQR 70 - 110). The median operative time was 45 (IQR 35 - 55) minutes and the hospital stay was 2 (IQR 1 - 2) days. Patients were discharged with the urinary catheter in place, which was removed approximately 7 days after surgery when the histopathological result was discussed with the patient. Postoperatively, IPSS, QoL, Qmax and PVR showed a significant improvement starting at 3 months and continued through the postoperative follow-up visits (6-12-24-36-48-60 months). Urethral stricture and bladder neck contracture occurred in 1 (0.45%) and 2 (0.91%) patients, respectively. Recurrence of BPH occurred in 2 patients (0.91%) who underwent a second procedure. Conclusions: In conclusion, we report that the multimodal surgical treatment of BPH consisting of combining Thulium laser vaporization, bipolar TURP and plasma vaporization (TLP) represents an efficient and durable therapeutic method for BPH patients with low a complication rate at 5-year follow-up.

Multimodal Approach Combining Thulium Laser Vaporization, Bipolar Transurethral Resection of the Prostate, and Bipolar Plasma Vaporization versus Bipolar Transurethral Resection of the Prostate: A Matched-Pair Analysis.

Background/Objectives: The aim of our study is to compare the perioperative and functional outcomes of a multimodal approach combining thulium laser vaporization, bipolar TURP, and bipolar plasma vaporization (TLP) with bipolar TURP in a matched-pair analysis. Methods: A nonrandomized, observational, retrospective, and matched-pair analysis was performed on two homogeneous groups of 60 patients who underwent TLP versus bipolar TURP at our center between March 2018 and December 2021. The American Society of Anesthesiologists (ASA) score and prostate volume (PV) were the main parameters used to match patients between the two groups. Follow-up was evaluated at 3, 6, 12, and 24 months after surgery. Results: There was a shorter operative time in favor of TLP (42 versus 45 min, p = 0.402). Median hemoglobin drop (-0.3 versus -0.6, p < 0.001) and median sodium drop (-0.3 versus -0.7, p < 0.001) after surgery were statistically significantly lower in TLP compared to bipolar TURP. The International Prostate Symptom Score (IPSS) and Quality of Life (QoL) scores were significantly lower, and the maximum urinary flow rate was higher in the TLP group. The median PSA decrease 2 years after surgery was 73.92% in the TLP group versus 76.17% in the bipolar TURP group (p = 0.578). The complication rate was lower in the TLP group (20% versus 21.67%, p = 1). Conclusions: The results show that both procedures are equally effective and safe in the treatment of symptomatic BPH with some advantages regarding the TLP technique.

Liver Phantoms Cast in 3D-Printed Mold for Image-Guided Procedures.

INTRODUCTION: Image-guided invasive procedures on the liver require a steep learning curve to acquire the necessary skills. The best and safest way to achieve these skills is through hands-on courses that include simulations and phantoms of different complications, without any risks for patients. There are many liver phantoms on the market made of various materials; however, there are few multimodal liver phantoms, and only two are cast in a 3D-printed mold. METHODS: We created a virtual liver and 3D-printed mold by segmenting a CT scan. The InVesalius and Autodesk Fusion 360 software packages were used for segmentation and 3D modeling. Using this modular mold, we cast and tested silicone- and gelatin-based liver phantoms with tumor and vascular formations inside. We tested the gelatin liver phantoms for several procedures, including ultrasound diagnosis, elastography, fibroscan, ultrasound-guided biopsy, ultrasound-guided drainage, ultrasound-guided radio-frequency ablation, CT scan diagnosis, CT-ultrasound fusion, CT-guided biopsy, and MRI diagnosis. The phantoms were also used in hands-on ultrasound courses at four international congresses. RESULTS: We evaluated the feedback of 33 doctors regarding their experiences in using and learning on liver phantoms to validate our model for training in ultrasound procedures. CONCLUSIONS: We validated our liver phantom solution, demonstrating its positive impact on the education of young doctors who can safely learn new procedures thus improving the outcomes of patients with different liver pathologies.

Intraoperative Ultrasound guided Palliative Radiofrequency Ablation of Unresectable Nonmetastatic Pancreatic Malignancies: A Pilot Observational Study.

BACKGROUND AND AIMS: Radiofrequency ablation of unresectable pancreatic tumors represents a palliative method in selected patients. The lack of standardization of the technique used as well as the non-homogeneous immediate and long-term results from the reports in the literature made us evaluate in a pilot study the application of a standardized technique through a surgical approach, with the evaluation of the immediate and long-term results. METHODS: Ten consecutive patients diagnosed with unresectable nonmetastatic pancreatic adenocarcinoma were referred for radio-frequency ablation by surgical approach. For that, a UniBlate (AngioDinamics®) internal cooled electrode was used, under intraoperative ultrasound guidance. We analysed the morbidity, mortality and survival associated with this procedure. The median follow-up period was 12 months. RESULTS: Intraoperative ultrasound was essential for guiding the procedure. No mortality and no major postoperative complications after intraoperative tumoral ablations were noted. The median survival after the procedure was 7.5 months. CONCLUSIONS: Radiofrequency intraoperative ablation of unresectable pancreatic tumors is a feasible procedure, with low morbidity and mortality if standardized, being noninferior to palliative chemotherapy alone in regards with survival. A larger study is necessary to demonstrate the potential benefits in survival, the role of multidisciplinary selection being also mandatory.

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.

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.

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.

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.

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.

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.

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).

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.

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.

Role of Metabolomics in Pathogenesis and Prompt Diagnosis of Gastric Cancer Metastasis-A Systematic Review.

INTRODUCTION: Gastric cancer is the fourth most frequently diagnosed form of cancer and the third leading cause of cancer-related mortality worldwide. The aim of this review is to identify individual metabolic biomarkers and their association with accurate diagnostic values, which can predict gastric cancer metastasis. MATERIALS AND METHODS: After searching the keywords, 83 articles were found over a period of 13 years. One was eliminated because it was not written in English, and two were published outside the selected period. Seven scientific papers were qualified for this investigation after eliminating duplicates, non-related articles, systematic reviews, and restricted access studies. RESULTS: New metabolic biomarkers with predictive value for gastric cancer metastasis and for elucidating metabolic pathways of the metastatic process have been found. The pathogenic processes can be outlined as follows: pro-oxidant capacity, T-cell inactivation, cell cycle arrest, energy production and mitochondrial enzyme impairment, cell viability and pro-apoptotic effect, enhanced degradation of collagen extracellular matrix, migration, invasion, structural protein synthesis, and tumoral angiogenesis. CONCLUSION: Metabolic biomarkers have been recognized as independent risk factors in the molecular process of gastric cancer metastasis, with good diagnostic and prognostic value.

Perineal Hernia Mesh Repair Using Only the Perineal Approach: How We Do It.

Perineal hernia is a rare complication of rectal surgery. Different types of surgical approach have been described, but none of them have proven their superiority. Although there are many methods of closing the defect, we selected two cases to present from a series of five cases, in which the perineal hernia was successfully resolved surgically using only the perineal approach. The reconstruction of the perineal floor and closure of the defect were performed using a synthetic polypropylene mesh. The significance of this Technical Note article lies in the fact that we describe, step by step, a surgical technique for perineal hernia using just a perineal approach.

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.

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.

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.