Topic Review
ICI-Based Combination Therapy for HCC
Advanced, unresectable hepatocellular carcinoma has a dismal outcome. Multiple immune checkpoint inhibitors (ICIs) targeting the programmed-cell death 1 pathway (PD-1/L1) have been approved for the treatment of advanced HCC. However, outcomes remain undesirable and unpredictable on a patient-to-patient basis. The combination of anti-PD-1/L1 with alternative agents, chiefly cytotoxic T-lymphocyte antigen-4 (CTLA-4) ICIs or agents targeting other oncogenic pathways such as the vascular endothelial growth factor (VEGF) pathway and the c-MET pathway, has, in addition to the benefit of directly targeting alterative oncogenic pathways, in vitro evidence of synergism through altering the genomic and function signatures of T cells and expression of immune checkpoints. Several trials have been completed or are underway evaluating such combinations. Finally, studies utilizing transcriptomics and organoids are underway to establish biomarkers to predict ICI response. 
  • 682
  • 06 May 2021
Topic Review
ICIs for HCC treatment
Immunotherapies are promising approaches for treating hepatocellular carcinomas (HCCs) refractory to conventional therapies. However, a recent clinical trial of immune checkpoint inhibitors (ICIs) revealed that anti-tumor responses to ICIs are not satisfactory in HCC cases. Therefore, it is critical to identify molecular markers to predict outcome and develop novel combination therapies that enhance the efficacy of ICIs. Recently, several attempts have been made to classify HCC based on genome, epigenome, and transcriptome analyses. These molecular classifications are characterized by unique clinical and histological features of HCC, as well immune phenotype. For example, HCCs exhibiting gene expression patterns with proliferation signals and stem cell markers are associated with the enrichment of immune infiltrates in tumors, suggesting immune-proficient characteristics for this type of HCC. However, the presence of activating mutations in β-catenin represents a lack of immune infiltrates and refractoriness to ICIs. Although the precise mechanism that links the immunological phenotype with molecular features remains controversial, it is conceivable that alterations of oncogenic cellular signaling in cancer may lead to the expression of immune-regulatory molecules and result in the acquisition of specific immunological microenvironments for each case of HCC. Therefore, these molecular and immune characteristics should be considered for the management of HCC using immunotherapy.
  • 708
  • 02 Nov 2020
Topic Review
Ileal Pouch–Anal Anastomosis and Pouchitis
Inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, are life-long disorders characterized by the chronic relapsing inflammation of the gastrointestinal tract with the intermittent need for escalation treatment and, eventually, even surgery. The total proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the surgical intervention of choice in subjects affected by ulcerative colitis (UC). Although IPAA provides satisfactory functional outcomes, it can be susceptible to some complications, including pouchitis as the most common.
  • 348
  • 18 Jul 2022
Topic Review
Image-Guided Locoregional Therapies (LRTs)
Image-guided locoregional therapies (LRTs) are a crucial asset in the treatment of hepatocellular carcinoma (HCC), which has proven to be characterized by an impaired antitumor immune status. LRTs not only directly destroy tumor cells but also have an immunomodulating role, altering the tumor microenvironment with potential systemic effects. 
  • 408
  • 15 Dec 2021
Topic Review
Imaging in Gastric Cancer
Gastric cancer represents one of the most common oncological causes of death worldwide. In order to treat patients in the best possible way, the staging of gastric cancer should be accurate. In this regard, endoscopy ultrasound (EUS) has been considered the reference standard for tumor (T) and nodal (N) statuses. However, thanks to technological improvements, computed tomography (CT) has gained an important role, not only in the assessment of distant metastases (M status) but also in T and N staging.
  • 387
  • 20 Apr 2023
Topic Review
Imaging in Portal Vein Thrombosis
The term portal vein thrombosis (PVT) refers to the complete or partial obstruction of blood flow in the portal vein, due to the presence of a thrombus in the vasal lumen. The underlying etiology of PVT remains unclear in up to 50% of children and adults. PVT, either primary or secondary to an underlying chronic liver disease, is the most common cause of prehepatic portal hypertension. On the one hand, primary PVT can be idiopathic, iatrogenic (neonatal umbilical vein catheterization), or related to an altered coagulation status. On the other hand, the progression of most chronic liver diseases leads to fibrosis, which increases sinusoid resistance and determines an abnormal elevation of portal venous pressure. The spontaneous development of a collateral circulation to divert the flow to the systemic circulation is the first observed anomaly, which itself contributes to PVT. 
  • 590
  • 11 Nov 2022
Topic Review
Immune Cells in Gastric Cancer
Despite the fact that the incidence of gastric cancer has declined over the last decade, it is still the world’s leading cause of cancer-related death. The diagnosis of early gastric cancer is difficult, as symptoms of this cancer only manifest at a late stage of cancer progression. Thus, the prognosis of gastric cancer is poor, and the current treatment for improving patients’ outcomes involves the application of surgery and chemotherapy. Immunotherapy is one of the most recent therapies for gastric cancer, whereby the immune system of the host is programmed to combat cancer cells, and the therapy differs based upon the patient’s immune system. However, an understanding of the role of immune cells, namely the cell-mediated immune response and the humoral immune response, is pertinent for applications of immunotherapy. The roles of immune cells in the prognosis of gastric cancer have yielded conflicting results.
  • 428
  • 23 Aug 2022
Topic Review
Immune Checkpoint Inhibitor-Related Pancreatitis
The indications for immune checkpoint inhibitors (ICIs) have expanded to include carcinomas of various organs. ICIs include drugs that target programmed cell death-1 (PD-1), programmed cell death ligand 1 (PDL-1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). The indications for these drugs have been expanded to include many types of cancer, as efficacies have been reported for malignant melanoma and lung, kidney, head and neck, stomach, liver, ovarian, and pancreatic cancers .
  • 990
  • 05 May 2022
Topic Review
Immune Classification of Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is a common and aggressive cancer with a high mortality rate. The incidence of HCC is increasing worldwide, and the lack of effective screening programs often results in delayed diagnosis, making it a challenging disease to manage. Immunotherapy has emerged as a promising treatment option for different kinds of cancers, with the potential to stimulate the immune system to target cancer cells. However, the current immunotherapeutic approaches for HCC have shown limited efficacy. Since HCC arises within a complex tumour microenvironment (TME) characterized by the presence of various immune and stromal cell types, the understanding of this interaction is crucial for the identification of effective therapy.
  • 275
  • 31 Jul 2023
Topic Review
Immune-Focused Pathophysiology of Hepatocellular Carcinoma
The emerging field of immuno-oncology has brought exciting developments in the treatment of hepatocellular carcinoma (HCC). It has also raised urgent questions about the role of immunotherapy in the setting of liver transplantation, both before and after transplant. A growing body of evidence points to the safety and efficacy of immunotherapeutic agents as potential adjuncts for successful down-staging of advanced HCCs to allow successful transplant in carefully selected patients. For patients with recurrent HCC post-transplant, immunotherapy has a limited, yet growing role.
  • 356
  • 17 Feb 2023
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