A critical analysis of surgical outcomes indicators in hepato-pancreato-biliary surgery: From crude mortality to composite outcomes.

Background: Indicators of surgical outcomes are designed to objectively evaluate surgical performance, enabling comparisons among surgeons and institutions. In recent years, there has been a surge in complex indicators of perioperative short-term and long-term outcomes. The aim of this narrative review is to provide an overview and a critical analysis of surgical outcomes indicators, with a special emphasis on hepato-pancreato-biliary (HPB) surgery.

Unveiling the prognostic role of blood inflammatory indexes in a retrospective cohort of patients undergoing liver resection for intrahepatic cholangiocarcinoma.

Background: Systemic inflammation is relevant in intrahepatic cholangiocarcinoma (iCCA), but controversial results exist on the prognostic role of inflammatory indexes and their correlation with tumor microenvironment. The authors aimed to explore the biological and prognostic values of these indexes.

Materials And Methods: A retrospective cohort study involving iCCA patients who underwent hepatic resection between 2010 and 2021 was conducted.

Cellular Senescence in Liver Cancer: How Dying Cells Become "Zombie" Enemies.

Liver cancer represents the fourth leading cause of cancer-associated death worldwide. The heterogeneity of its tumor microenvironment (TME) is a major contributing factor of metastasis, relapse, and drug resistance. Regrettably, late diagnosis makes most liver cancer patients ineligible for surgery, and the frequent failure of non-surgical therapeutic options orientates clinical research to the investigation of new drugs.

Clinical and Molecular Characteristics of Gonadotroph Pituitary Tumors According to the WHO Classification.

Since 2017, hormone-negative pituitary neuroendocrine tumors expressing the steroidogenic factor SF1 have been recognized as gonadotroph tumors (GnPT) but have been poorly studied. To further characterize their bio-clinical spectrum, 54 GnPT defined by immunostaining for FSH and/or LH (group 1, n = 41) or SF1 only (group 2, n = 13) were compared and studied for SF1, βFSH, βLH, CCNA2, CCNB1, CCND1, caspase 3, D2R, and AIP gene expression by qRT-PCR. Immunohistochemistry for AIP and/or D2R was performed in representative cases.

Cholangiocarcinoma-on-a-chip: A human 3D platform for personalised medicine.

Background & Aims: Cholangiocarcinoma (CCA) is a primary liver tumour characterised by a poor prognosis and limited therapeutic options. Available 3D human CCA models fail to faithfully recapitulate the tumour niche. We aimed to develop an innovative patient-specific CCA-on-chip platform.

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.

Cancer-on-chip: a 3D model for the study of the tumor microenvironment.

The approval of anticancer therapeutic strategies is still slowed down by the lack of models able to faithfully reproduce in vivo cancer physiology. On one hand, the conventional in vitro models fail to recapitulate the organ and tissue structures, the fluid flows, and the mechanical stimuli characterizing the human body compartments. On the other hand, in vivo animal models cannot reproduce the typical human tumor microenvironment, essential to study cancer behavior and progression.

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.

Surgical Strategies for Recurrent Hepatocellular Carcinoma after Resection: A Review of Current Evidence.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and both liver resection and liver transplantation are considered potentially curative options. However, high recurrence rates affect the prognosis depending both on the primary HCC pathology characteristics or on the type and time of the relapse. While great attention has been usually posted on treatment algorithms for the first HCC, treatment algorithms for recurrent HCC (rHCC) are lacking.

Relationship between Epithelial-to-Mesenchymal Transition and Tumor-Associated Macrophages in Colorectal Liver Metastases.

The liver is the most common metastatic site in colorectal cancer (CRC) patients. Indeed, 25-30% of the cases develop colorectal liver metastasis (CLM), showing an extremely poor 5-year survival rate and resistance to conventional anticancer therapies. Tumor-associated macrophages (TAMs) provide a nurturing microenvironment for CRC metastasis, promoting epithelial-to-mesenchymal transition (EMT) through the TGF-β signaling pathway, thus driving tumor cells to acquire mesenchymal properties that allow them to migrate from the primary tumor and invade the new metastatic site.

Experimental liver models: From cell culture techniques to microfluidic organs-on-chip.

The liver is one of the most studied organs of the human body owing to its central role in xenobiotic and drug metabolism. In recent decades, extensive research has aimed at developing in vitro liver models able to mimic liver functions to study pathophysiological clues in high-throughput and reproducible environments. Two-dimensional (2D) models have been widely used in screening potential toxic compounds but have failed to accurately reproduce the three-dimensionality (3D) of the liver milieu.

Tumor microenvironment in primary liver tumors: A challenging role of natural killer cells.

In the last years, several studies have been focused on elucidate the role of tumor microenvironment (TME) in cancer development and progression. Within TME, cells from adaptive and innate immune system are one of the main abundant components. The dynamic interactions between immune and cancer cells lead to the activation of complex molecular mechanisms that sustain tumor growth.

Impact of RAS mutations on the immune infiltrate of colorectal liver metastases: A preliminary study.

Kirsten rat sarcoma viral oncogene homolog KRAS proto-oncogene is the most common altered gene in colorectal cancer (CRC). Determining its mutational status, which is associated with worse prognosis and resistance to anti-epidermal growth factor receptor (EGFR) inhibitors, is essential for managing patients with CRC and colon liver metastases (CLM). Emerging studies highlighted the relationship of KRAS-mutated cancers and tumor microenvironment components, mainly with T cells.

Expression of Peroxisome Proliferator-Activated Receptor Alpha (PPARα) in Non-Somatotroph Pituitary Tumours and the Effects of PPARα Agonists on MMQ Cells.

Peroxisome proliferator-activated receptor alpha (PPARα) has been involved in the regulation of somatotroph tumour cells and may be targeted by different drugs, some of them are in current clinical use. The aim of this study was to investigate the expression of PPARα in additional phenotypes of pituitary adenomas (PA), the relationship between PPARα and its potential molecular partner aryl hydrocarbon receptor interacting protein (AIP) in these tumours, and the effects of PPARα agonists on lactotroph cells. Seventy-five human PA - 57 non-functioning (NFPA) and 18 prolactinomas (PRL-PA) - were characterised for PPARα and AIP expression by real time RT-PCR and/or immunohistochemistry (IHC), and the effects of fenofibrate and WY 14 643 on MMQ cells were studied in vitro.