New Relevant Evidence in Cholangiocarcinoma Biology and Characterization.

Among solid tumors, cholangiocarcinoma (CCA) emerges as one of the most difficult to eradicate. The silent and asymptomatic nature of this tumor, particularly in its early stages, as well as the high heterogeneity at genomic, epigenetic, and molecular levels delay the diagnosis, significantly compromising the efficacy of current therapeutic options and thus contributing to a dismal prognosis. Extensive research has been conducted on the molecular pathobiology of CCA, and recent advances have been made in the classification and characterization of new molecular targets.

CT-radiomics and pathological tumor response to systemic therapy: A predictive analysis for colorectal liver metastases. Development and internal validation of a clinical-radiomic model.

Introduction: The standard treatment of colorectal liver metastases (CRLM) is surgery with perioperative chemotherapy. A tumor response to systemic therapy confirmed at pathology examination is the strongest predictor of survival, but it cannot be adequately predicted in the preoperative setting. This bi-institutional retrospective study investigates whether CT-based radiomics of CRLM and peritumoral tissue provides a reliable non-invasive estimation of the pathological tumor response to chemotherapy.

Ganglioside GD2 Contributes to a Stem-Like Phenotype in Intrahepatic Cholangiocarcinoma.

Background & Aims: GD2, a member of the ganglioside (GS) family (sialic acid-containing glycosphingolipids), is a potential biomarker of cancer stem cells (CSC) in several tumours. However, the possible role of GD2 and its biosynthetic enzyme, GD3 synthase (GD3S), in intrahepatic cholangiocarcinoma (iCCA) has not been explored.

Methods: The stem-like subset of two iCCA cell lines was enriched by sphere culture (SPH) and compared to monolayer parental cells (MON).

Hepatocellular Carcinoma Immune Microenvironment Analysis: A Comprehensive Assessment with Computational and Classical Pathology.

Purpose: The spatial variability and clinical relevance of the tumor immune microenvironment (TIME) are still poorly understood for hepatocellular carcinoma (HCC). In this study, we aim to develop a deep learning (DL)-based image analysis model for the spatial analysis of immune cell biomarkers and microscopically evaluate the distribution of immune infiltration.

Experimental Design: Ninety-two HCC surgical liver resections and 51 matched needle biopsies were histologically classified according to their immunophenotypes: inflamed, immune-excluded, and immune-desert.

Link between persistent, unexplained gamma-glutamyltransferase elevation and porto-sinusoidal vascular disorder.

Background & Aims: Porto-sinusoidal vascular disorder (PSVD) is a group of vascular disorders characterized by lesions involving portal venules and sinusoids, irrespective of the presence of portal hypertension. Liver biopsy is essential for diagnosis. In a single-center study, we demonstrated high rates of PSVD in patients with persistently elevated gamma-glutamyltransferase (GGT).

Challenge of concomitant thymoma resection and myocardial revascularization: A Case Report.

Myocardial revascularization in patients presenting with an anterior mediastinal mass poses considerable challenges. In this report, we outline two cases involving patients with anterior mediastinal masses who underwent surgical resection alongside concurrent myocardial revascularization. One patient underwent coronary artery bypass graft surgery, while the other was treated by percutaneous coronary intervention with drug-eluting stent placement.

CT-based radiogenomics of intrahepatic cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive disease with increasing incidence and its genetic alterations could be the target of systemic therapies.

Aims: To elucidate if radiomics extracted from computed tomography (CT) may non-invasively predict ICC genetic alterations.

Methods: All consecutive patients with a diagnosis of a mass-forming ICC (01/2016-06/2022) were considered.

The tumor microenvironment of VETC+ hepatocellular carcinoma is enriched of immunosuppressive TAMs spatially close to endothelial cells.

Background And Aim: VETC (vessel that encapsulate tumor cluster) is a peculiar vascular phenotype observed in hepatocellular carcinoma (HCC), associated with distant metastases and poor outcome. VETC has been linked to the Tie2/Ang2 axis and is characterized by lymphocytes poor (cold) tumor microenvironment (TME). In this setting the role of Tumor Associated Macrophages (TAMs) has never been explored.

Autoimmunity in thymic epithelial tumors: a not yet clarified pathologic paradigm associated with several unmet clinical needs.

Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against "self". In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma.

Asymptomatic giant ascending aortic aneurysm: a challenging surgical strategy for a silent bicuspid aortopathy.

We report the case of an incidental finding of a huge aneurysm of the ascending aorta with a congenital bicuspid aortic valve type 0-lateral. This severe condition was totally unknown to the patient, who was asymptomatic for cardiovascular disease. The aneurysmal mass involved the entire mediastinum, altering the normal anatomical relations, so the operative strategy was modified intraoperatively, tailoring the surgical technique to the anatomical conditions found.

Filamin A is involved in human intrahepatic cholangiocarcinoma aggressiveness and progression.

Background & Aims: Intrahepatic cholangiocarcinoma (iCCA) is a primary liver tumour, characterized by poor prognosis and lack of effective therapy. The cytoskeleton protein Filamin A (FLNA) is involved in cancer progression and metastasis, including primary liver cancer. FLNA is cleaved by calpain, producing a 90 kDa fragment (FLNA ) that can translocate to the nucleus and inhibit gene transcription.

Artificial intelligence-based pathology as a biomarker of sensitivity to atezolizumab-bevacizumab in patients with hepatocellular carcinoma: a multicentre retrospective study.

Background: Clinical benefits of atezolizumab plus bevacizumab (atezolizumab-bevacizumab) are observed only in a subset of patients with hepatocellular carcinoma and the development of biomarkers is needed to improve therapeutic strategies. The atezolizumab-bevacizumab response signature (ABRS), assessed by molecular biology profiling techniques, has been shown to be associated with progression-free survival after treatment initiation. The primary objective of our study was to develop an artificial intelligence (AI) model able to estimate ABRS expression directly from histological slides, and to evaluate if model predictions were associated with progression-free survival.

Preoperative systemic inflammatory markers as prognostic factors in differentiated thyroid cancer: a systematic review and meta-analysis.

Background: Inflammation has been associated with tumor development and circulating inflammatory biomarkers have been proposed as possible predictors of recurrence of several solid tumors. However, the role of inflammation markers in differentiated thyroid carcinoma (DTC) is still uncertain.

Objective: This meta-analysis aimed to assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in patients with DTC.

Exploring a novel composite method using non-contrast EUS enhanced microvascular imaging and cyst fluid analysis to differentiate pancreatic cystic lesions.

Background And Aims: Differentiating pancreatic cystic lesions (PCLs) remains a diagnostic challenge. The use of high-definition imaging modalities which detect tumor microvasculature have been described in solid lesions. We aim to evaluate the usefulness of cystic microvasculature when used in combination with cyst fluid biochemistry to differentiate PCLs.

Tumor-infiltrating lymphocytes and tumor-associated macrophages as potential predictors of lymph node metastases in major salivary gland cancers.

Purpose: The purpose of this study is to define if tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) could represent potential predictors of lymph node metastases (LNM) in salivary gland cancers (SGC).

Methods: A selected number of immunohistochemical markers related to TILs (CD3, CD4, CD68, and FOXP3) and TAMs (CD68 and CD163) were investigated on major salivary gland cancers. TIL and TAM densities were measured on digital images using the open-source QuPath both in the tumor interior (TI) and invasive margin (IM).

The complementary role of PSMA expression and [F]FDG PET/CT in predicting thyroid cancer outcome: from black and white to shades of gray, in the era of precision oncology.

Background: The value of Prostate Specific Membrane Antigen (PSMA) in thyroid carcinoma (TC) is still unknown. We aimed to test the potential complementary role of PSMA expression and 2-[F]fluoro-2-deoxy-D-glucose ([F]FDG) uptake on PET/CT as biomarkers for TC outcome prediction.

Materials And Methods: From a retrospective cohort of TC patients we selected those fulfilling the following inclusion/exclusion criteria: thyroidectomy in our Institution, available primary tumor tissue PSMA immunostaining, [F]FDG PET/CT and follow-up data.

Macrophage morphology and distribution are strong predictors of prognosis in resected colorectal liver metastases: results from an external retrospective observational study.

Introduction: Tumor-associated macrophages (TAMs) are key components of a tumoral microenvironment and have been shown to impact prognosis in different cancers. Previously reported data showed that TAM morphology correlates with prognosis in colorectal liver metastases (CLMs) after hepatectomy, with smaller TAMs (S-TAMs) conferring a more favorable prognosis than larger ones (L-TAMs). This study aims to externally validate this finding.

Combined Inhibition of Smoothened and the DNA Damage Checkpoint WEE1 Exerts Antitumor Activity in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is characterized by resistance to chemotherapy and a poor prognosis. Therefore, treatments that can effectively suppress tumor growth are urgently needed. Aberrant activation of hedgehog (HH) signaling has been implicated in several cancers, including those of the hepatobiliary tract.

Prognostic Impact of Tumor Immune Microenvironment and Its Predictive Role in Salivary Gland Cancer.

Background: Recently, many studies have investigated the role of tumor immune microenvironment (TIME) in carcinogenesis, highlighting its relation to both tumor regression and progression. In particular, the "inflammatory system", made of innate and adaptive immune cells, interacts with cancer cells and their surrounding stroma. In this setting, the aim of this review is to summarize the current literature regarding the TIME of major salivary gland carcinomas (MSGCs), with particular attention on the characteristics and prognostic role of tumor infiltrating lymphocytes (TILs), the mechanisms that lead to TILs exhaustion and the important additional immune infiltrating factors that help SGC progression or remission.