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Impact of direct-acting antivirals on the recurrence of hepatocellular carcinoma in chronic hepatitis C
No full textChronic hepatitis C virus (HCV) infection is estimated to affect 56.8 million individuals globally and is a major and independent risk factor for the development of hepatocellular carcinoma (HCC). After the introduction of safe and potent direct-acting antivirals (DAAs), capable of curing HCV infection also in patients with advanced liver disease at high risk of HCC, the beneficial effect on a de novo HCC development after viral clearance has been established. However, studies addressing the relationship between DAA-induced eradication and risk of HCC recurrence (i.e., reappearance of HCC treated before starting antivirals) have produced contradictory data, suggesting either an increase or a decrease of HCC recurrence rate, while some report no effect of these treatments. Thus, there seems to be an unclear benefit of viral clearance in patients with a history of HCC curative treatment, where the recurrence rate remains worryingly high. This short review aims to summarize current evidence on the impact of DAAs on HCC recurrence rates, the pathogenic mechanisms and characteristics of HCC recurrence after DAA treatment, the predictors of tumor recurrence, and the impact of DAAs on overall survival
Alteration in immune function in patients with fatty liver disease
No full textNonalcoholic fatty liver disease (NAFLD) is a disease spectrum that spans simple steatosis, fibrosis, and ultimately cirrhosis, and is a leading cause of chronic liver disease globally. The severe variant of NAFLD, non-alcoholic steatohepatitis (NASH), is characterized by triglyceride accumulation within hepatocytes and the subsequent inflammatory pathway activation, ultimately progressing to cirrhosis in 10%-20% of patients. NASH is a known major risk factor for the development of hepatocellular carcinoma (HCC), and there is emerging data demonstrating the impact of NASH on immune subsets and the tumor microenvironment that may influence therapeutic response. This review describes the various ways in which the immune system is altered in patients with NASH. The innate immune system in NASH shows alterations in dendritic and Kupffer cells, impaired cytotoxicity of Natural Killer cells, and an accumulation of neutrophils. Additionally, there is emerging evidence emphasizing the role of the adaptive immune system in the development and progression of NASH, seen in the alteration of B-cells, T-cells, and NKT Cells. Due to the complex interplay of the immune system in NAFLD/NASH and its progression to HCC, many current treatments focus on targeting immune cells for HCC therapy. Recently, immune checkpoint inhibitors such as atezolizumab and bevacizumab have been approved as first-line therapy for unresectable HCC. Although an emerging field of research, further studies and clinical trials are needed to understand the complex interface of NASH, HCC and the immune response
Taking on the elephant in the room-postoperative atrial fibrillation: a clinical program management perspective
No full textPostoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery, yet there is no consistent cardiothoracic professional society-based definition of new-onset POAF, nor a broadly accepted consensus on how to prevent or treat it. Importantly, there is an ever-growing body of evidence that new-onset POAF is associated with worse patient outcomes. Given the lack of evidence-based guidelines, detection and treatment of POAF, in addition to understanding how POAF is related to these worse outcomes, represents an unaddressed quality of care concern. In the United States, the annual cardiac surgical POAF patient costs are estimated at ~141.2 billion for all hospital-related care; thus, the administrative challenges uniquely posed by POAF have been exposed for the first time. Mapping future tactics, this Vessel Plus special atrial fibrillation publication, swings the pendulum from impromptu observations towards action. A new strategic framework is proposed to begin the tedious but necessary task of taking on this elephant in the room. With ideal collaboration between clinical providers, health care systems, professional societies and insurers, a five-step approach is proposed to overcome these POAF patient care challenges
Technology's role in the emergence of collaborative, multidisciplinary foregut societies
No full textRobot-assisted flexible ureterorenoscopy: state of the art in 2022
No full textDue to the technical improvements in endoscopes and armamentarium, flexible ureterorenoscopy (fURS) has increased in the management of nephrolithiasis over the last decade. fURS is a challenging procedure and therefore limited in some regions. To overcome these challenges, a master-slave robotic system might help dominate fURS. As with other robotic systems, the ergonomic deficits of fURS play an important role in the development of a new robot. All ureterorenoscopy (URS) robots thus far consist of a surgeon’s console and the manipulator of a flexible ureterorenoscope. Handling and maneuverability of the different systems vary, but the master-salve system is common to all robots. Optimal ergonomics and comparable surgical results to conventional flexible URS demonstrate the successful use of some of these robots. In this narrative review, we provide an update on the robot-assisted flexible ureterorenoscopy, the different systems, and the final role and future perspective of robotic fURS
Robotic radical prostatectomy in post HIFU salvage setting: tertiary center experience and review of the current literature
No full textAim: The purpose of the study was to describe our surgical technique of salvage robot-assisted radical prostatectomy (sRARP) in patients who underwent primary high-intensity focused ultrasound (HIFU) and to report the perioperative, functional, and oncological outcomes during the first year follow up. The secondary aim of the study was to review the current literature evidence on this topic.Methods: We retrospectively extracted, from our prospective RARP database, all the patients who underwent sRARP for biochemical recurrence after primary HIFU. All the surgical interventions were performed by a single surgeon following our total anatomical reconstruction (TAR) technique. Demographics, perioperative, functional, and oncological results were collected up to one year follow-up.Results: Eleven patients underwent post-HIFU sRARP with TAR technique at our institution. All the surgical procedures were uneventful. All the complication recorded were classified as Clavien-Dindo Grade I. Continence rate at 1-, 3-, 6-, and 12-month post intervention was 36.3%, 45.5%, 63.6 %, and 81.1%, respectively. Medium PSA at 12 months follow-up was 0.2 ng/mL (SD 0.01), with no Biochemical Failure (BCF) recorded.Conclusion: sRARP with TAR technique is a safe and feasible procedure in patients with BCF after primary HIFU. No major complications were recorded, with good oncological and functional results after one year follow up
Exosome secretion from hypoxic cancer cells reshapes the tumor microenvironment and mediates drug resistance
No full textHypoxia is a common phenomenon in solid tumors as the poorly organized tumor vasculature cannot fulfill the increasing oxygen demand of rapidly expanding tumors. Under hypoxia, tumor cells reshape their microenvironment to sustain survival, promote metastasis, and develop resistance to therapy. Exosomes are extracellular vesicles secreted by most eukaryotic cells, including tumor cells. They are enriched with a selective collection of nucleic acids and proteins from the originating cells to mediate cell-to-cell communication. Accumulating evidence suggests that exosomes derived from tumor cells play critical roles in modulating the tumor microenvironment (TME). Hypoxia is known to stimulate the secretion of exosomes from tumor cells, thereby promoting intercellular communication of hypoxic tumors with the surrounding stromal tissues. Exosome-mediated signaling pathways under hypoxic conditions have been reported to cause angiogenesis, invasion, metastasis, drug resistance, and immune escape. Recently, the programmed cell death ligand-1 (PD-L1) has been reported to reside as a transmembrane protein in tumor exosomes. Exosomal PD-L1 was shown to suppress T cell effector function in the TME and cause drug resistance to immune checkpoint therapy. This review provides an update about the pivotal role of tumor-derived exosomes in drug resistance to chemotherapy and immunotherapy, particularly under hypoxic conditions. Emerging strategies that target the exosomes in the hypoxic TME to enhance the antitumor efficacy are discussed
An overview of resistance to chemotherapy in osteosarcoma and future perspectives
No full textOsteosarcoma (OS) is the most common type of bone sarcoma. Despite the availability of multimodal treatment with surgery and chemotherapy, the clinical results remain unsatisfactory. The main reason for the poor outcomes in patients with OS is the development of resistance to methotrexate, cisplatin, doxorubicin, and ifosfamide. Molecular and cellular mechanisms associated with resistance to chemotherapy include DNA repair and cell-cycle alterations, enhanced drug efflux, increased detoxification, resistance to apoptosis, autophagy, tumor extracellular matrix, and angiogenesis. This versatility of cells to generate chemoresistance has motivated the use of anti-angiogenic therapy based on tyrosine kinase inhibitors. This approach has shown that other therapies, along with standard chemotherapy, can improve responses to therapy in patients with OS. Moreover, microRNAs may act as predictors of drug resistance in OS. This review provides insight into the molecular and cellular mechanisms involved in the development of resistance during the treatment of OS and discusses promising novel therapies (e.g., afatinib and palbociclib) for overcoming resistance to chemotherapy in OS
Genetic risk and its role in primary prevention of CAD
No full textCoronary artery disease (CAD) is a pandemic disease and the number one cause of death in the world. Predisposition to CAD is about 50% acquired and 50% genetic. CAD prevention has been proven in randomized clinical trials with statin therapy. However, primary prevention is limited by the lack of biomarkers to detect asymptomatic young individuals at risk. Traditional risk factors (TRFs) such as hypertension or Type 2 Diabetes are age-dependent and often not present until the sixth or seventh decade. In contrast, genetic risk determined at conception is potentially a biomarker to detect young individuals at risk for CAD. The first genetic risk variant for CAD (9p21) was discovered in 2007, and subsequently, over 200 risk variants for CAD were discovered. A genetic risk score (GRS) based on the genetic risk variants for CAD was evaluated in over one million individuals. Retrospective analysis of clinical trials assessing the effect of statin therapy showed that individuals with the highest GRS had the highest risk for cardiac events and also the most benefit from lowering cholesterol. In a recent study of 55,685 individuals, those with the highest GRS (20%) had a 91% higher risk for cardiac events. Furthermore, those with high genetic risk on a favorable lifestyle had 46% fewer cardiac events than those with an unfavorable lifestyle. The GRS is superior and independent of TRFs. Incorporation into clinical practice will be a paradigm shift in preventing this pandemic
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