Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death and the sixth most diagnosed malignancy worldwide. Serum alpha-fetoprotein (AFP) is the traditional, ubiquitous biomarker for HCC. However, there has been an increasing call for the use of multiple biomarkers to optimize care for these patients. AFP, AFP-L3, and prothrombin induced by vitamin K absence II (DCP) have described clinical utility for HCC, but unfortunately, they also have well established and significant limitations. Circulating tumor DNA (ctDNA), genomic glycosylation, and even totally non-invasive salivary metabolomics and/or micro-RNAS demonstrate great promise for early detection and long-term surveillance, but still require large-scale prospective validation to definitively validate their clinical validity. This review aims to provide an update on clinically available and emerging biomarkers for HCC, focusing on their respective clinical strengths and weaknesses.

Background: Histotripsy is a novel, non-invasive, non-ionizing, and non-thermal ablation technique that disrupts tumors using acoustic cavitation. We report the first use of Histotripsy as bridging therapy prior to liver transplant for hepatocellular carcinoma (HCC) treated with histotripsy. Case presentation: A 59-year-old woman presented with Metabolic-Associated Steatotic Liver Disease (MASLD) cirrhosis (labMELD = 14), hepatic encephalopathy, and a single 2 cm OPTN V lesion in the left lateral segment consistent with HCC. The patient underwent histotripsy treatment of the lesion as bridging therapy before receiving liver transplantation. Histopathology analysis of the explanted liver showed total necrosis of the treated area, with no residual viable tissue tumor. Conclusion: This case demonstrates the potential utility of histotripsy as an effective bridging therapy for patients with combined cirrhosis and hepatocellular carcinoma (HCC) awaiting liver transplantation, with complete tumor necrosis on explant pathology demonstrating its therapeutic efficacy.

Liver malignancies, both primary and metastatic tumors, are a major cause of cancer-related mortality. Colorectal cancer alone results in liver metastases in nearly 50% of patients, with approximately 85% presenting with unresectable disease. Similarly, hepatocellular carcinoma and intrahepatic cholangiocarcinoma frequently present at advanced stages, limiting curative options. Systemic therapies provide modest survival benefits, underscoring the need for alternative treatments. Locoregional approaches, such as thermal ablation and chemoembolization, while effective, have notable limitations, including invasiveness, peri-procedural risks, and the requirement to interrupt systemic treatments. Histotripsy is a novel, non-invasive method that uses focused ultrasound-induced cavitation to enable precise tumor ablation without heat or radiation. Our institution utilizes a multidisciplinary tumor board approach to evaluate patients for histotripsy, particularly in cases involving unresectable disease, complex surgical candidacy, palliative intent related to disease control and symptom management, or as bridging therapy for transplantation. Early results, including preclinical data and the THERESA and #HOPE4LIVER trials, highlight its efficacy in treating liver tumors with minimal complications. This review outlines institutional protocols for histotripsy, covering pre- and post-procedural management, along with ethical considerations of current treatment paradigms. As a patient-centered approach, histotripsy offers a novel treatment option with a favorable safety profile and compatibility with systemic therapies.

Cholangiocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts, with poor prognosis and limited treatment options. Traditional therapies, such as surgery, chemotherapy, and radiation, have shown limited efficacy, especially in advanced cases. Recent advancements in immunotherapy, particularly T cell-based therapies like chimeric antigen receptor T (CAR T) cells, tumor-infiltrating lymphocytes (TILs), and T cell receptor (TCR)-based therapies, have opened new avenues for improving outcomes in CCA. This review provides a comprehensive overview of the current state of T cell therapies for CCA, focusing on CAR T cell therapy. It highlights key challenges, including the complex tumor microenvironment and immune evasion mechanisms, and the progress made in preclinical and clinical trials. The review also discusses ongoing clinical trials targeting specific CCA antigens, such as MUC1, EGFR, and CD133, and the evolving role of precision immunotherapy in enhancing treatment outcomes. Despite significant progress, further research is needed to optimize these therapies for solid tumors like CCA. By summarizing the most recent clinical results and future directions, this review underscores the promising potential of T cell therapies in revolutionizing CCA treatment.

Background: The impact of near-infrared autofluorescence (NIRAF) imaging on postthyroidectomy hypocalcemia is controversial. As patients with Graves' disease are at increased risk, our aim was to compare postoperative parathyroid function in these patients undergoing total thyroidectomy (TT) with or without NIRAF imaging. Methods: This was a retrospective “before and after” study, comparing outcomes of patients who underwent TT without or with NIRAF imaging at a single center. Primary outcome was the incidence of temporary hypocalcemia and secondary outcomes, rates of incidental parathyroidectomy on final specimens and permanent hypocalcemia. Analyses were performed using Mann-Whitney U and chi-Square tests. Continuous data are expressed as median (interquartile range). Results: There were 85 patients in NIRAF and 100 patients in non-NIRAF group. Groups were comparable regarding age, gender, body-mass index, and thyroid weight. Number of parathyroid glands identified intraoperatively was 3 in both groups ( p = 0.47). Intraoperative parathyroid implantation rate was 16.5% in NIRAF and 6% in non-NIRAF group ( p = 0.02). Incidental parathyroidectomy rate on final pathology was 12.9% in NIRAF and 32% in non-NIRAF group ( p = 0.002). The rates of temporary (11.7% vs. 16%) and permanent hypocalcemia (2.4% vs. 2%) were similar between the two groups, respectively ( p = 0.66). Conclusion: To our knowledge, this is the first comparative study investigating the impact of NIRAF on postoperative parathyroid function after thyroidectomy for Graves' disease. The rate of incidental parathyroidectomy on final pathology was lower with use of NIRAF, without an impact on temporary or permanent hypocalcemia rates compared to conventional technique.

Colorectal cancer is a leading cause of cancer-related mortality, with nearly 50% of patients developing liver metastases (CRLM). Unfortunately, 85% of patients present with unresectable disease. Systemic chemotherapy offers limited survival benefits, and thus alternative therapies are urgently needed. Lo-coregional approaches such as thermal ablation and chemoembolization, while effective, have notable limitations, including invasiveness, peri-procedural risks, and required interruption of systemic treatments. Histotripsy is a novel, non-invasive method that uses focused ultrasound-induced cavitation to enable precise tumor ablation without heat or radiation. Our institution utilizes a multidisciplinary tumor board approach to evaluate patients for histotripsy, particularly in cases involving unresectable disease, complex surgical candidacy, palliative intent, or as a bridging therapy for transplantation. Early results, including preclinical data and the THERESA and #HOPE4LIVER trials, highlight its efficacy in treating liver tumors with minimal complications. Herein, we discuss institutional protocols for histotripsy including pre- and post-procedure management, and ethical discussion of current approaches. Histotripsy represents a promising, patient-centered approach for CRLM, especially for patients not eligible for traditional thera-pies, due to its favorable safety profile and compatibility with systemic treatments.