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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. [ABSTRACT FROM AUTHOR]

Solid-organ malignancies represent a significant disease burden and remain one of the leading causes of death globally. In the past few decades, the rapid evolution of imaging modalities has shifted the paradigm towards image-based precision medicine, especially in the care of patients with solid-organ malignancies. Metabolic tumor volume (MTV) is one such semi-quantitative parameter obtained from positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose (FDG) that has been shown to have significant implications in the clinical oncology setting. Across various solid tumor malignancies, including lung cancer, head and neck cancer, breast cancer, esophageal cancer, and colorectal cancer, the current literature has demonstrated an association between MTV and various clinical outcomes. MTV may be used in conjunction with several existing and established clinical parameters to help inform risk stratification and treatment strategies and predict outcomes in cancer. Optimizing such volumetric parameters is paramount for advancing efforts to advance cancer care for our patients. While such advancements are made, it is important to investigate and address the limitations of MTV, including variability in terms of measurement methods, a lack of standardized cut-off values, and the impact of inherent tumor heterogeneity. Despite these limitations, which can precipitate challenges in standardization, MTV as a prognostic factor has great potential and opens an avenue for the future integration of technology into an image-based precision medicine model of care for cancer patients. This article serves as a narrative review and explores the utility and limitations of PET-MTV in various settings of solid-organ malignancy. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver transplantation (LT) is a key treatment for liver cancers by reducing tumor burden and improving liver function. While LT offers significant improvement in survival, cancer recurrence rates remain high. Ischemia-reperfusion injury (IRI) caused by mitochondria dysfunction drives tumor recurrence by creating a favorable pro-inflammatory microenvironment. Therefore, strategies that decrease IRI may also decrease cancer recurrence following LT. Machine perfusion techniques are increasingly used in routine clinical practice of LT with improved post-transplant outcomes. Normothermic (NMP) and hypothermic oxygenated machine perfusion (HOPE) provide oxygen to ischemic tissues, and impact IRI and potential cancer recurrence through different mechanisms. This article discussed the link between IRI-associated inflammation and tumor recurrence after LT and examined the role of machine perfusion as a strategy to mitigate the risk of cancer recurrence. Upfront NMP ("ischemia free organ transplantation") and end-ischemic HOPE were shown to reduce hepatocellular carcinoma recurrence in retrospective studies. Liver transplantation (LT) is a key treatment for primary and secondary liver cancers, reducing tumor burden with concurrent improvement of liver function. While significant improvement in survival is noted with LT, cancer recurrence rates remain high. Mitochondrial dysfunction caused by ischemia-reperfusion injury (IRI) is known to drive tumor recurrence by creating a favorable microenvironment rich in pro-inflammatory and angiogenic factors. Therefore, strategies that decrease reperfusion injury and mitochondrial dysfunction may also decrease cancer recurrence following LT. Machine perfusion techniques are increasingly used in routine clinical practice of LT with improved post-transplant outcomes and increased use of marginal grafts. Normothermic (NMP) and hypothermic oxygenated machine perfusion (HOPE) provide oxygen to ischemic tissues, and impact IRI and potential cancer recurrence through different mechanisms. This article discussed the link between IRI-associated inflammation and tumor recurrence after LT. The current literature was screened for the role of machine perfusion as a strategy to mitigate the risk of cancer recurrence. Upfront NMP ("ischemia free organ transplantation") and end-ischemic HOPE were shown to reduce hepatocellular carcinoma recurrence in retrospective studies. Three prospective randomized controlled trials are ongoing in Europe to provide robust evidence on the impact of HOPE on cancer recurrence in LT. [ABSTRACT FROM AUTHOR]

Background: Open offers (OOs) in liver transplantation (LT) result from bypassing the traditional allocation system. Little is known about the trends of OOs or the differences in donor/recipient characteristics compared to traditionally placed organs. We aim to quantify modern practices regarding OOs and understand NMP's impact, focusing on social determinants of health (SDH), cost, and graft‐associated risk. Methods: LTs from 1/1/2018 to 12/31/2023 at a single center were included. NMP was implemented on 10/1/2022. The CDC (centers for disease control)‐validated social vulnerability index (SVI) and donor risk index (DRI) were calculated. Comprehensive complications index (CCI), Clavien‐Dindo grades, patient and graft survival, and costs of transplantation were included. Results: 1162 LTs were performed; 193 (16.8%) from OOs. OOs were more common in the post‐NMP era (26.5% vs. 13.3%, p < 0.001). Pre‐NMP, patients receiving OOs had longer waitlist times (118 vs. 69 days, p < 0.001), lower MELDs (17 vs. 25 points, p < 0.001), and riskier grafts (DRI = 1.8 vs. 1.6, p = 0.004) compared to standard offers. Post‐NMP, recipients receiving OOs demonstrated no difference in waitlist time (27 vs. 20 days, p = 0.21) or graft risk (DRI = 2.03 vs. 2.23, p = 0.17). OO recipient MELD remained lower (16 vs. 22, p < 0.001). OO recipients were more socially vulnerable (SVI), pre‐NMP (0.41 vs. 0.36, p = 0.004), but less vulnerable after NMP (0.23 vs. 0.36, p = 0.019). Despite increased graft risk, pre‐NMP OO‐LTs were less expensive in the 90‐day global period ($154 939 vs. $178 970, p = 0.002) and the 180‐days pre‐/post‐LT ($208 807 vs. $228 091, p = 0.021). Cost trends remained similar with NMP. Conclusion: OOs are increasingly utilized and may be appealing due to demonstrated cost reductions even with NMP. Although most OO‐related metrics in our center remain similar before and after machine perfusion, programs should take caution that increasing use does not worsen organ access for socially vulnerable populations. [ABSTRACT FROM AUTHOR]

Objective: To quantify the rate of progression in surveilled cysts and assess what factors should indicate delayed resection. Background: Side-branch intraductal papillary mucinous neoplasms (SB-IPMNs) are increasingly discovered, making it challenging to identify which patients require resection, thus avoiding inappropriate treatment. Most incidental lesions are surveyed, yet the consequences of that decision remain uncertain. Methods: A prospectively maintained database of pancreatic cystic neoplasms was queried for patients with SB-IPMN. Patients with ≥ 2 imaging studies >6 months apart were included. Clinically relevant progression (CR-progression) was defined by symptoms, worrisome/high-risk stigmata, or invasive cancer (IC). Growth ≥ 5 mm in 2 years is considered CR-progression; size ≥3 cm alone is not. Results: Between 1997 and 2023, 1337 patients were diagnosed with SB-IPMN. Thirty-seven (2.7%) underwent up-front surgery; 1000 (75.0%) had >6 months of surveillance. The rate of CR-progression was 15.3% (n = 153) based on size increase (n = 63, 6.3%), mainduct involvement (n = 48, 4.8%), symptoms (n = 8, 5.0%), or other criteria (n = 34, 3.4%). At a median follow-up of 6.6 years (interquartile range: 3.0-10.26), 17 patients (1.7%) developed IC. Those with CR-progression developed IC in 11.1% (n = 17) and highgrade dysplasia (HGD) in 6.5% (n = 10). Nearly half of the cancers were not contiguous with the surveyed SB-IPMN. Size ≥3 cm was not associated with HGD/IC (P = 0.232). HGD/IC was least common in CR-progression determined by size growth (6.3%) versus main-duct involvement (24%) or other (43%, P < 0.001) Patients with CR-progression demonstrated improved survival (overall survival) with resection on time-to-event (P < 0.001) and multivariate Cox regression (hazard ratio = 0.205, 0.096-0.439, P < 0.001) analyses. Overall survival was not improved with resection in all patients (P = 0.244). Conclusions: CR-progression for SB-IPMNs is uncommon, with the development of cancer anywhere in the pancreas being rare. Initial size should not drive resection. Long-term and consistent nonoperative surveillance is warranted, with surgery currently reserved for CR-progression, knowing that the majority of these still harbor low-grade pathology. [ABSTRACT FROM AUTHOR]

Simple Summary: This review article explores the potential of CAR T cell therapy in treating cholangiocarcinoma (CCA), a highly aggressive and difficult-to-treat cancer of the bile ducts. With conventional therapies offering limited success, this article highlights the innovative approach of using immune cell therapy, particularly CAR T cells, to improve outcomes for CCA patients. The review discusses the tumor microenvironment's role in disease progression and the challenges of implementing CAR T cell therapy in solid tumors. By summarizing current research, clinical trials, and the evolving landscape of precision medicine, this article aims to provide a comprehensive understanding of the future prospects for immunotherapy in CCA, emphasizing the need for continued advancements in this promising field. 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. [ABSTRACT FROM AUTHOR]