Search Results (143)

Background/Objectives: ¹⁸F-PSMA-1007 is one of the more widely used radioligands in prostate cancer imaging with PET/CT. Its major advantage lies in the low urinary tracer activity due to primarily hepatobiliary clearance, but unexpectedly high tracer accumulation in the bladder can occur, potentially hindering assessment of lesions near the prostate bed. This study assesses the impact of furosemide on ¹⁸F-PSMA-1007 tracer accumulation in the bladder. Methods: In this single-center, retrospective, intra-individual comparative analysis, 18 patients undergoing two consecutive ¹⁸F-PSMA-1007 PET/CT scans for biochemical relapse (BCR) or persistence (BCP)—one with and one without prior furosemide administration—were included. Images were acquired 60 min post-injection of 250 MBq of tracer activity. Standardized Uptake Values (SUVmax, SUVpeak, SUVmean) were measured in the bladder and in tissues with physiological uptake by three readers. Differences were analyzed using Wilcoxon signed-rank tests. The inter-reader agreement was assessed using intraclass correlation coefficient. Results: Furosemide significantly decreased bladder SUVmax, SUVpeak, and SUVmean (all p < 0.001). Mean bladder SUVmax decreased from 13.20 ± 10.40 to 3.92 ± 3.47, SUVpeak from 10.94 ± 8.02 to 3.47 ± 3.13, and SUVmean from 8.74 ± 6.66 to 2.81 ± 2.56, representing a large effect size (r ≈ 0.55). Physiological tracer uptake in most organs was not significantly influenced by furosemide (all p > 0.05). Conclusions: Despite the predominantly hepatobiliary clearance of ¹⁸F-PSMA-1007, furosemide-induced forced diuresis leads to a significant reduction in tracer activity in the bladder, which in clinical practice could help in early detection of tumor recurrence. Full article

The 26th annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Saskatoon, Saskatchewan, on 17–18 October 2024. The WCGCCC is an interactive multidisciplinary conference that was attended by healthcare professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with hepatocellular and biliary tract cancers. Specialists from the fields of medical and radiation oncology, interventional radiology, pathology and laboratory medicine, and general and hepatobiliary surgery participated in presentations and discussions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of hepatocellular and biliary tract cancers. Full article

Hepatobiliary diseases, which include disorders of the liver, gallbladder, and bile ducts, remain a major global health concern. A significant proportion of deaths worldwide are attributed to hepatic diseases, accounting for 4% of the total global mortality in 2023. Among benign hepatobiliary diseases, metabolic dysfunction-associated steatotic liver disease is the most prevalent liver pathology, with a concerning rise in incidence, while it is recognized as the leading cause of liver transplantation in the United States. However, there is a notable rise over time in cases of autoimmune hepatobiliary disorders, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Meanwhile, hepatocellular carcinoma still remains the most frequently diagnosed hepatobiliary malignancy, constituting the third leading cause of malignancy-related mortality globally. Meanwhile, cholangiocarcinoma and gallbladder cancer are the second and third most common hepatobiliary malignancies, respectively, both exhibiting highly aggressive malignant behavior. Despite the notable advances in biomarkers and the development of therapeutic tools, early diagnosis and monitoring are considered pivotal for the management of the aforementioned pathologies. The development of new non-invasive biomarkers that can effectively identify, monitor these pathologies, and guide their management is considered a necessity. Extracellular vesicles (EVs) constitute nanoparticles with several embedded cargoes, with a significant role in intercellular communication, which are considered promising biomarkers in several diseases, including viral, metabolic, autoimmune, and malignant diseases. In this review, we will shed light on the role of EVs as novel frontiers in hepatobiliary diseases. Full article

Background: The advent of newer pharmacological agents, particularly proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors, in combination with conventional lipid-lowering treatments, has allowed for the significant lowering of low-density lipoprotein cholesterol (LDL-C). However, it is unclear if very low LDL-C levels achieved with the use of PCSK-9 inhibitors are associated with increased adverse events that may outweigh potential benefits. Methods: A systematic search of PubMed, Medline, and Cochrane databases was conducted from their inception to 21 February 2025, for randomized controlled trials (RCTs) reporting clinical outcomes with intensive lipid-lowering treatment with PCSK-9 inhibitors leading to very low (<40 mg/dL) LDL-C levels vs. a control group with higher LDL-C levels. The outcomes of interest included the incidence of major adverse cardiovascular events (MACEs), neurocognitive disorders, diabetes mellitus, muscle disorders, any adverse events, events leading to drug discontinuation, cataract, hepatobiliary disorders, and cancer. Random effects meta-analysis models were used to calculate the pooled incidence and odds ratio (OR) with 95% confidence intervals (Cis). Results: A total of six RCTs with 52,951 patients (11,209 very low LDL-C, and 41,742 control) met the inclusion criteria. Compared with patients in the control arm, very low LDL-C was associated with a reduction in MACEs (OR = 0.76, 95% CI: 0.64, 0.89; p < 0.01; I² = 44.8%). The incidence of most safety outcomes including neurocognitive disorders, diabetes mellitus, muscle disorders, any adverse events, events leading to drug discontinuation, cataract, hepatobiliary disorders, and cancer were comparable between the very low LDL-C and control groups. Conclusions: Very low LDL-C values following intensive lipid-lowering with PCSK-9 inhibitors are associated with a major reduction in cardiovascular events without any significant increase in serious side effects. Full article

Background: Photodynamic therapy (PDT) utilizing nano-based photosensitizers (PSs) offers promising cancer treatment potential but requires rigorous safety evaluation. Conjugated polymer nanoparticles (CPNs) doped with porphyrins, such as platinum porphyrin–doped poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT), exhibit enhanced photodynamic efficiency but lack comprehensive preclinical toxicity data. This study aimed to evaluate the biocompatibility, biodistribution, and acute/subacute toxicity of these CPNs to establish their safety profile for clinical translation. Methods: CPNs were synthesized via nanoprecipitation using amphiphilic stabilizers (PSMA or PS-PEG-COOH) and characterized for colloidal stability in parenteral solutions. Hemolysis assays were used to assess blood compatibility. Single-dose (0.3 and 1 mg/kg, intravenous) and repeated-dose (0.1–1 mg/kg, intraperitoneal, every 48 h for 28 days) toxicity studies were conducted in BALB/c mice. Hematological, biochemical, histopathological, and biodistribution analyses (via ICP-MS) were performed to evaluate systemic and organ-specific effects. Results: CPNs demonstrated excellent colloidal stability in 5% dextrose, with minimal aggregation. No hemolytic activity was observed at concentrations up to 50 mg/L. Single and repeated administrations revealed no significant changes in body/organ weights, hematological parameters (except transient fibrinogen elevation), or liver/kidney function markers (ALT, AST, BUN, Cr). Histopathology showed preserved tissue architecture in major organs, with mild hepatocyte vacuolation at 30 days. Biodistribution indicated hepatic/splenic accumulation and rapid blood clearance, suggesting hepatobiliary elimination. Conclusions: Platinum porphyrin–doped F8BT CPNs exhibited minimal acute and subacute toxicity, favorable biocompatibility, and no systemic adverse effects in murine models. These findings support their potential as safe PS candidates for PDT. However, chronic toxicity studies are warranted to address long-term organ accumulation and metabolic impacts. This preclinical evaluation provides a critical foundation for advancing CPNs toward clinical applications in oncology. Full article

Transplant oncology integrates a wide variety of fields, such as surgery, oncology, and transplant medicine, intending to increase the range of studies and treatments for hepatobiliary cancers and other liver-related malignant lesions. Liver transplantation (LT) has proven to be an effective treatment for hepatocellular carcinoma. While the Milan criteria are still the gold standard, several new, more inclusive criteria have been proposed, and hepatocellular carcinoma has become a major indication for liver transplantation. The continuous evolution of diagnostic technologies supported this with higher image quality and more accurate staging. This review describes the current applications of transplant oncology in hepatocellular carcinoma, cholangiocarcinoma, neuroendocrine tumors, and liver metastatic disease from colorectal cancer and discusses the path that led to the development of transplant oncology as an organized approach to managing gastrointestinal malignancies through transplantation. More importantly, the significance of a multidisciplinary approach and criteria in the selection of suitable candidates are discussed. In addition, newer aspects of transplant oncology, such as immunotherapy, circulating tumor DNA (ctDNA), novel surgical techniques, and the utilization of artificial intelligence, are presented. Finally, the opportunities and challenges involved in the field’s future, as well as the evolution of the criteria used over the years and insightful thoughts for the future of the criteria, are discussed. Full article

Background: Hepatobiliary liver cancers (HBLCs) represent the sixth most common neoplasm in the world. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) constitute the main HBLC types, with alarming epidemiological projections. Methods: In recent decades, alterations in gut microbiota, with mutual implications on the gut–liver axis and gut–biliary axis permeability status, have been massively investigated and proposed as HBLC pathogenetic deus ex machina. Results: In the HCC setting, elevated intestinal levels of Escherichia coli and other Gram-negative bacteria have been demonstrated, resulting in a close association with increased lipopolysaccharide (LPS) serum levels and, consequently, chronic systemic inflammation. In contrast, the intestinal microbiota of HCC individuals feature reduced levels of Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. In the CC setting, evidence has revealed an increased expression of Lactobacillus spp., with enhanced levels of Actynomices spp. and Alloscardovia spp. Besides impaired strains/species representation, gut-derived metabolites, including bile acids (BAs), short-chain fatty acids (SCFAs), and oxidative-stress-derived products, configure a network severely impacting the progression of HBLC. Conclusions: In the era of Precision Medicine, the clarification of microbiota composition and functioning in HCC and CC settings can contribute to the identification of individual signatures, potentially providing novel diagnostic markers, therapeutic approaches, and prognostic/predictive tools. Full article

Background/Objectives: Indocyanine green (ICG) fluorescence imaging is widely utilized for visualizing hepatic tumors, hepatic segmentation, and biliary anatomy, improving the safety and curability of cancer surgery. However, its application for perfusion assessment in hepatobiliary and pancreatic (HBP) surgery has been less explored. Methods: This study evaluated outcomes of patients undergoing HBP surgery with vascular reconstruction from April 2022 to August 2024. During surgery, ICG (1.25–5 mg/body) was administered intravenously to assess the need and quality of vascular reconstruction via fluorescence imaging. Results: Among 30 patients undergoing hepatectomies and/or pancreatectomies, ICG fluorescence imaging was used in 16 cases (53%) to evaluate organ and vascular perfusion. In two hepatectomy cases with consideration of reconstruction of the middle hepatic veins, sufficient fluorescence intensities in drainage areas led to the avoidance of middle hepatic vein reconstruction. In 14 cases requiring vascular reconstruction, fluorescence imaging visualized smooth blood flow through anastomotic sites in 11 cases, while insufficient signals were observed in 3 cases. Despite this, re-do anastomoses were not indicated because the fluorescence signals in the targeted organs were adequate. Postoperative contrast-enhanced computed tomography confirmed satisfactory blood perfusion in all cases. Conclusions: Real-time blood flow assessment using ICG fluorescence imaging provides valuable information for intraoperative decision-making in HBP surgeries that require vascular reconstruction of major vessels, such as hepatic arteries, veins, and the portal system. Full article

Intrahepatic abscess is an exceedingly rare complication of locoregional therapy for patients with liver cancer. However, in patients who underwent prior hepatobiliary intervention, the incidence of liver abscess increases significantly, causing morbidity and even mortality in such patients. Here, we will review the relative risk of developing a liver abscess after intraarterial and ablative locoregional therapies in patients with liver cancer depending on whether they underwent any kind of prior hepatobiliary procedures that resulted in violation of the Ampulla of Vater. As a result, patients deemed at high risk of developing a liver abscess were treated prophylactically, with the combination of bowel preparation and antibiotics nearly eliminating the occurrence of a liver abscess after locoregional therapy. Therefore, given the significant risk of developing a liver abscess in patients with prior hepatobiliary procedures, management consisting of prophylactic bowel preparation with antibiotic coverage followed by antibiotics post-locoregional therapy is recommended. Full article

Background/Objectives: Over the past four years, ⁶⁸Ga-fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) has been established at a tertiary cancer care facility in Jordan. This retrospective study aims to explore tracer uptake metrics across various epithelial neoplasms, identify diagnostic pitfalls associated with ⁶⁸Ga-FAPI PET/CT, and evaluate the influence of ⁶⁸Ga-FAPI PET/CT staging results on changes in therapeutic intent compared to gold standard molecular imaging modalities. Methods: A total of 48 patients with biopsy-confirmed solid tumors underwent 77 ⁶⁸Ga-FAPI PET/CT examinations for molecular imaging assessment, encompassing neoplasms originating from the gastrointestinal tract, head and neck, hepatobiliary system, pancreas, breast, and lung. Results: Notably, pancreaticobiliary tumors exhibited the highest tracer uptake, with mean maximum standardized uptake values (SUVmax) and tumor-to-background ratios (TBR) surpassing 10. A comparative sub-analysis of ⁶⁸Ga-FAPI PET metrics in 20 treatment-naïve patients revealed a significant correlation between ⁶⁸Ga-FAPI uptake metrics and tumor grade (Spearman’s rho 0.83; p = 0.00001). Importantly, the results from ⁶⁸Ga-FAPI PET/CT influenced treatment decisions in 35.5% of the cases, primarily resulting in an escalation of management plans. A total of 220 diagnostic challenges were identified across 88.3% of the scans, predominantly within the musculoskeletal system, attributed to degenerative changes (99 observations). Conclusions: This comprehensive analysis highlights the potential significance of ⁶⁸Ga-FAPI PET/CT in oncological imaging and treatment strategy, while also emphasizing the necessity for meticulous interpretation to mitigate diagnostic challenges. Full article

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 subfamily is particularly interesting because of its unique protein structure and role in endocrine function. The abnormal expression of FGFs in different cancer types (breast, colorectal, hepatobiliary, bronchogenic, and others) is examined and correlated with patient prognosis. The classification of FGF ligands based on their mode of action, whether autocrine, paracrine, endocrine, or intracrine, is illustrated, and an analysis of the binding specificity of FGFs to FGFRs is also provided. Moreover, the latest advances in cancer therapeutic strategies involving small molecules, ligand traps, and monoclonal antibody-based FGF inhibitors are presented. Lastly, we discuss how the dysregulation of FGF and FGFR expression affects FGF signaling and its role in cancer development. Full article

Background: Immuno-oncology has transformed cancer treatment, with immune checkpoint inhibitors (ICIs) like pembrolizumab playing a key role. While highly effective, these therapies can also cause immune-related adverse events. This study examines the incidence and characteristics of hepatobiliary adverse events (AEs) linked to pembrolizumab, using data from the FDA Adverse Event Reporting System (FAERS). Objective: To investigate the rates of hepatobiliary AEs linked to pembrolizumab, providing insights into the risks of liver and biliary system damage in patients prescribed pembrolizumab. Methods: This study utilized the FAERS database via OpenVigil 2.1. Adverse events (AEs) related to pembrolizumab were identified and compared to those associated with other drugs. Reporting odds ratios (RORs) were calculated to assess the likelihood of hepatobiliary AEs in pembrolizumab-treated patients. Results: In total, 594 hepatic AEs and 181 biliary AEs were identified. Significant hepatic AEs included elevated ALT (ROR 3.00, 95% CI: 2.685–3.351), hepatotoxicity (ROR 6.436, 95% CI: 5.72–7.242), and hepatic cytolysis (ROR 15.721, 95% CI: 13.854–17.84). Immune-mediated hepatitis exhibited the highest ROR of 346.716 (95% CI: 303.568–395.997). For biliary AEs, cholangitis (ROR 19.597, 95% CI: 16.852–22.791) and sclerosing cholangitis (ROR 24.735, 95% CI: 19.888–30.763) were the most prominent. Conclusions: Pembrolizumab is associated with a significant risk of hepatobiliary adverse events, particularly immune-mediated hepatitis and cholangitis. The elevated RORs for these conditions highlight the importance of close monitoring and managing liver and biliary functions in patients undergoing pembrolizumab checkpoint blockade. These findings emphasize the need for personalized treatment strategies to mitigate risks and optimize outcomes in cancer immunotherapy, especially for those with preexisting hepatobiliary conditions. Full article

Background: Previously, we reported elevated levels of fucosylated α₁-acid glycoprotein (fAGP) in plasma samples from patients with diverse types of cancers. Accordingly, fAGP was assumed to be a potential biomarker for the early detection of cancers. Methods: The fAGP level was retrospectively measured in preoperative plasma samples from 213 patients with either hepatic, biliary tract, or pancreatic cancer and was analyzed together with levels of six existing tumor markers determined as reference standards. Results: When the cutoff value was set at 25.45 U/μg, elevated levels of fAGP were significantly observed in cancer patients. The sensitivity, specificity, and accuracy for the detection of malignancy in these diseases were determined to be 70.79, 51.72, and 68.12, respectively. In contrast, all the tumor markers exhibited low sensitivity and accuracy, even though they commonly had extremely high (≥80%) specificity. Further, a significant number of patients in both early and advanced clinical stages were found to be false negative in these tumor makers but were found to be positive in the fAGP level. A dramatic improvement in the diagnosis by tumor markers in such patients with all clinical stages was found by the determination of the fAGP level. This indicated that fAGP could serve to correct false-negative diagnosis with tumor markers. Conclusions: It is believed that fAGP could be a relevant, unique, and highly sensitive biomarker for early diagnosis of hepatobiliary and pancreatic cancers. Full article

Background: Advances in cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have improved outcomes for selected patients with peritoneal surface malignancies (PSMs). Methods: This retrospective study analyzed 743 PSM patients treated at Fondazione Policlinico Universitario Agostino Gemelli from January 2016 to February 2024. The primary aim was to assess median overall survival (mOS), median disease-free survival (mDFS), and median progression-free survival (mPFS) stratified by tumor origin. Secondary outcomes examined the role of diagnostic laparoscopy in the management of PSMs and intra- and postoperative complications’ rates. Results: A total of 1113 procedures were performed: 389 CRS, 370 PIPAC, and 354 diagnostic laparoscopies. Colorectal cancer was the predominant indication for CRS (52.4%), with a mOS of 52 months and mDFS of 22 months. Patients affected by gastric cancer undergoing CRS had a mOS of 18 months and a mDFS of 13 months, while PIPAC yielded a mOS of 9 months and a mPFS of 4 months. Among patients with pseudomyxoma peritonei undergoing CRS, the 5-year DFS rate was 64.1%, and OS rate was 89%. Patients affected by mesothelioma and treated with CRS exhibited a median OS of 43 months and a DFS of 26 months. Pancreatic and hepatobiliary cancers were treated with PIPAC, with a respective mOS of 12 and 8 months. Postoperative complications occurred in 12.6% of CRS, 3.2% of PIPAC, and 1.7% of diagnostic laparoscopies. High peritoneal cancer index (PCI), gastric resection, and blood loss over 500 mL were identified as risk factors for major complications in a multivariate analysis. Conclusions: Developing a highly experienced multidisciplinary team is crucial for delivering tailored treatment strategies which aim to achieve optimal oncological outcomes while preserving patients’ quality of life. Full article

Primary sclerosing cholangitis (PSC) and Primary biliary cholangitis (PBC) are chronic inflammatory biliary diseases characterized by progressive damage of the bile ducts, resulting in hepatobiliary fibrosis and cirrhosis. Currently, specific biomarkers that allow to distinguish between PSC and PBC do not exist. In this study, we examined the salivary proteome by carrying out a comprehensive and non-invasive screening aimed at highlighting possible quali-quantitative protein deregulations that could be the starting point for the identification of effective biomarkers in future. Saliva samples collected from 6 PBC patients were analyzed using a liquid chromatography–tandem mass spectrometry technique, and the results were compared with those previously obtained in the PSC group. We identified 40 proteins as significantly deregulated in PSC patients compared to the PBC group. The Gene Ontology and pathway analyses highlighted that several proteins (e.g., small integral membrane protein 22, cofilin-1, macrophage-capping protein, plastin-2, and biliverdin reductase A) were linked to innate immune responses and actin cytoskeleton remodeling, which is a critical event in liver fibrosis and cancer progression. These findings provide new foundations for a deeper understanding of the pathophysiology of PSC and demonstrate that saliva is a suitable biological sample for obtaining proteomic fingerprints useful in the search for biomarkers capable of discriminating between the two cholestatic diseases. Full article