Silencing OGFOD1 ameliorates hepatic ischemia-reperfusion injury through abrogating oxidative stress and apoptosis via downregulating SPARC.

Minimally invasive techniques for resection of centrally located tumors near the region of hepatic duct bifurcation poses technical concerns to many hepatobiliary surgeons. Excessive bleeding, inadvertent injury to the hilar plate with subsequent bile leak and abdominal sepsis, and involvement of the middle hepatic vein (MHV) often deter surgeons from using a minimally invasive technique in this circumstance. An emerging robotic method with advantages over conventional laparoscopy offers greater technical feasibility for peri-/juxtahilar dissections and MHV ligation/reconstruction. Although robotic portal vein resection and reconstruction has been established and widely reported in the literature, especially in pancreaticoduodenectomy or Klatskin tumor resection,1-5 technical descriptions of hepatic vein reconstruction remain limited. Herein, we describe our technique for robotic partial central hepatectomy for juxtahilar tumor, highlighting steps of MHV tangential reconstruction to avoid congestion of the associated hepatic parenchyma drained by the MHV trunk. A 57-year-old woman presented with a single 5 cm segment V hypermetabolic mass, concerning for metastatic breast cancer without evidence of extrahepatic disease. She had a multifocal invasive adenocarcinoma requiring partial mastectomy and antiestrogen treatment 11 years before her current presentation. Magnetic resonance imaging showed a 5 cm liver mass almost in contact with the hepatic duct bifurcation dorsally and laterally displacing the middle portion of the MHV. Robotic partial central hepatectomy under intermittent Pringle maneuver was undertaken using a meticulous crush-clamp technique to avoid injury to the hilar plate, and tangential reconstruction of the MHV using a curved vascular bulldog clamp was completed without intraoperative complications. The robotic operation was completely uneventful, with minimal blood loss, and the patient had an uneventful recovery followed by hospital discharge on postoperative day 3. A final pathology report was consistent with metastatic breast cancer with negative resection margins. At 16 months after the robotic liver resection, the patient remains without evidence of disease recurrence. Although robotic approaches to resection and reconstructive techniques for the portal vein and inferior vena cava have been discussed, very little is known about resection and reconstructive techniques for the major hepatic vein during robotic hepatic resection. Preservation of the major hepatic vein, such as MHV, is important to avoid parenchymal venous congestion of the corresponding liver sector, which in theory can compromise overall liver function in patients with marginal future liver remnant volume or hepatic functional reserve secondary to underlying liver disease. In the case presented here, the right anterior sector (segment 5/8) is dominant, with 37% portion volume, so adequate parenchymal venous drainage via MHV was clinically important and necessary. Adequate inflow, outflow, and biliary drainage are three widely known key factors that determine postoperative hepatic recovery and parenchymal regeneration. Another observation on the preoperative imaging was that a segment IV bile duct was focally dilated because of mechanical local tumor compression/involvement onto the segmental bile duct, which was directly located dorsal to this mass. Beyond this localized radiological finding, no clinical symptoms were observed. The tumor did not invade the roof of the hilar plate, so R-0 resection margins were easily obtained. A hepatic vein reconstruction technique such as shown in this video can be similarly applied for other major hepatic veins such as the right and left hepatic veins. We anticipate that this robotic technique for reconstructing major hepatic veins will become significantly more relevant in cases of upper segmental tumor resection, as reported by Procopio et al.6 As such, tumor resection using a robotic approach can be maximally optimized. Application of a robotic technique is safe and feasible for juxtahilar tumors requiring precise dissection and reconstruction of the major hepatic vein trunk. We believe that the robotic surgical system allows for challenging hepatic tumor resections in difficult locations and hepatic vascular preservation using reconstructive techniques.

ASO Author Reflections: A Surgical Video of an Ex Vivo Liver Resection with Autotransplantation in a Case with Extensive Inferior Vena Cava Leiomyosarcoma Extending to the Right Atrium with Atrial Septal Involvement and Complete Occlusion of All Major Hepatic Veins.

Objective: To compare and analyze the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs) as adjuvant therapy after surgery for hepatocellular carcinoma (HCC) with microvascular invasion (MVI). Methods: Patients with HCC accompanied with MVI who underwent R0 liver resection at the First Medical Center of the PLA General Hospital between January 2016 and December 2024 were retrospectively enrolled. The clinicopathological data, surgical details, and follow-up data were recorded. Adverse events after medication were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Recurrence-free survival (RFS) and overall survival (OS) curves were plotted using the Kaplan-Meier method and compared with the Log-rank test. The Cox proportional hazards regression model was used to analyze factors influencing recurrence. Results: The study included 39 patients in the adjuvant therapy group and 41 patients in the follow-up observation group. There were no significant differences in baseline characteristics between the two groups (all P>0.05). The follow-up time [M(Q1, Q3)] was 21.8 (10.9, 50.7) months. The RFS rates at 6, 12, 24, and 36 months in the adjuvant therapy group were 92.3%, 76.0%, 71.2%, and 51.8%, respectively, all higher than those in the follow-up observation group (75.1%, 56.3%, 44.3%, and 16.9%). The median RFS in the adjuvant therapy group was 46.7 months (95%CI:15.19-78.22), significantly better than the 19.33 months (95%CI: 3.22-35.44) in the follow-up observation group (P=0.004). The median OS was not reached in either group(P=0.480). Multivariate Cox analysis showed that postoperative adjuvant therapy (HR=0.46, 95%CI: 0.24-0.89, P=0.020) and liver cirrhosis (HR=2.22, 95%CI: 1.00-4.92, P=0.050) were influencing factors for RFS. In terms of safety, 43.59% (17/39) of patients in the adjuvant therapy group experienced grade 1-4 adverse events, and 15.38% (6/39) experienced grade 3 or higher adverse events, primarily manifested as abnormal liver and kidney function, rash, etc. No treatment-related deaths occurred, and the safety profile was manageable. Conclusion: For patients with HCC accompanied by MVI, postoperative adjuvant therapy with immunotherapy combined with targeted therapy significantly prolongs recurrence-free survival, reduces the risk of recurrence, and demonstrates a manageable safety profile.

Early postoperative edema and ascites after liver resection are common; however, the endocrine drivers of water retention are not fully defined. Arginine vasopressin (AVP) promotes antidiuresis via V2-mediated aquaporin trafficking, whereas the renin-angiotensin-aldosterone system primarily modulates sodium handling. Differences in postoperative trajectories and their relationship to early fluid retention have not been clarified in patients undergoing liver resection. To examine postoperative changes in plasma AVP and plasma aldosterone concentration (PAC) after liver resection, and association with fluid retention. We conducted a prospective cohort study of adults undergoing elective liver resection at a tertiary center. Blood samples were collected preoperatively, immediately post-resection, and on postoperative days (POD) 1, 2, 3, and 5. The primary objective was characterizing postoperative dynamics of AVP and PAC. Secondary objectives evaluated their temporal alignment with early fluid retention (body weight, urine output during POD 1-3) and compared hormonal profiles between major and minor resections. Analyses used trajectory and time-based comparisons by resection extent. AVP increased sharply immediately after resection and remained above the preoperative baseline through POD 3, showing the most pronounced and sustained elevation after major liver resection. In contrast, PAC showed a transient postoperative increase that returned to near-baseline levels by POD 2. The period of elevated AVP closely matched the time frame during which early postoperative fluid retention was most evident, as indicated by greater short-term weight gain and reduced urine output. These patterns were consistent across sensitivity analyses and showed similar directional trends in subgroup comparisons based on resection extent. AVP remains elevated longer than aldosterone and coincides with early fluid retention, particularly after major resection. Vasopressin-driven antidiuresis may be important in postoperative water retention.

Background. In unresectable hepatoblastoma (HB), particularly “pre-treatment extent of tumor” (PRETEXT) IV tumors or those with positive annotation factors, standard management consists of intensive chemotherapy followed by surgical resection or orthotopic liver transplantation (OLT). Radiotherapy has traditionally been avoided because of the liver’s radiosensitivity and the risk of radiation-induced liver disease. Proton beam therapy (PBT), owing to its dosimetric advantage and ability to spare uninvolved liver parenchyma, may represent a potential local control strategy in selected pediatric patients for whom curative surgery or OLT is not feasible. Case Presentation. We describe five pediatric patients with advanced hepatoblastoma treated with proton beam therapy at our institution between February 2022 and January 2024. The cohort included three girls and two boys, with a median age of 3.0 years (interquartile range [IQR], 1.6–4.0) and a median alpha-fetoprotein level of 435,453 ng/mL (IQR: 7,668–1,276,681) at diagnosis. All patients were initially considered inoperable because of extensive hepatic involvement, inadequate future liver remnant, or multifocal disease, and OLT was not feasible owing to donor limitations or medical comorbidities. All received neoadjuvant chemotherapy using SIOPEL-based regimens, achieving partial tumor response. Tumors ranged from 5 to 12 cm and involved central hepatic segments, the portal region, or both lobes. PBT was delivered at a total dose of 50 GyE in 10–25 fractions as definitive or consolidative therapy, followed by surgical resection in three patients. Two patients additionally received targeted therapy and immunotherapy. At last follow-up, four patients were alive with no evidence of disease, while one patient died from tumor progression. Conclusions. These cases suggest that proton beam therapy may serve as a feasible liver-sparing local treatment option for selected pediatric patients with unresectable or residual hepatoblastoma when surgery or OLT is not possible. While limited by availability and cost, PBT may facilitate multimodal therapy and preserve future treatment options.

The definition of textbook outcome (TO) for liver surgery in patients with intrahepatic cholangiocarcinoma (ICC) varies depending on the data and TO model utilized in the study. This study aimed to clarify the separate estimation of TO in relation to its negative predictors, using two validated TO models for ICC surgery. We assessed the rates of achieving TO and failure of TO for both models in liver resection. Independent predictors of non-TO were identified through logistic regression and validated using AUC estimation. TO was achieved in a similar proportion of patients across both models: 40% and 43%. The TO models did not differ in preoperative data affecting TO achievement. Independent predictors of non-TO for both models included tumor size > 10 cm,, open surgical approach, and biliary resection. TO achievement significantly differed among sub-groups that were homogeneous concerning the opposing values of the independent predictors, regardless of the TO model. The ratio of the frequency of negative predictors in the TO and non-TO groups, referred to as the TO coefficient, determines the likelihood of achieving TO given the presence of that predictor. Predictors were ranked by their negative impact on TO achievement, from the highest risk of TO failure (tumor size > 10 cm) to the lowest risk (open approach). Independent predictors of non-TO may improve the transparency of TO assessment and reduce biases related to unaccounted negative prognostic factors. The impact of these independent predictors on TO realization can be estimated and ranked using TO coefficient calculations.

Robotic liver resection for primary and metastatic hepatobiliary cancer. A decade single-center experience on perioperative and overall survival outcomes.

Meta-analysis: robot-assisted vs. laparoscopic liver resection for early stage HCC

Transforming liver cancer care: long-term outcomes of robotic liver resection for hepatocellular cancer.

Surgical resection of liver and lung metastases in breast cancer is increasingly considered a viable option for select patients with oligometastatic disease. Historically regarded as palliative, surgery is now supported by retrospective data suggesting potential survival benefits, particularly in patients with hormone receptor-positive or HER2-positive tumors, long disease-free intervals, and limited metastatic burden. This narrative review summarizes recent evidence on the surgical management of breast cancer metastases to the liver and lung, with a focus on patient selection, perioperative outcomes, and long-term survival. Liver metastasectomy has shown 5-year overall survival rates of up to 60% in well-selected patients, while pulmonary metastasectomy is associated with comparable outcomes when resection is complete and nodal involvement is absent. Minimally invasive techniques and non-surgical approaches, such as microwave ablation and stereotactic radiotherapy, expand treatment options for patients unfit for surgery. The review also explores emerging tools influencing surgical decision-making, including circulating tumor DNA for minimal residual disease detection, transcriptomic profiling to predict organotropism, and artificial intelligence (AI)-driven platforms that assist with surgical planning and multidisciplinary case evaluation. While prospective validation remains limited, these technologies may help redefine surgical candidacy through biologically informed algorithms. Ultimately, the integration of surgery within a multimodal, personalized treatment strategy-guided by systemic control, tumor biology, and evolving digital tools-represents an evolving and biologically informed direction for rigorously selected patients with visceral breast cancer metastases.

Limitations of adult post-hepatectomy liver failure criteria in pediatric liver tumor surgery: A single-center retrospective study.

Procedure-dependent impact of non-dialysis chronic kidney disease on outcomes after liver resection for hepatocellular carcinoma.

The impact of perioperative chemotherapy, including neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC), given for resectable colorectal liver metastasis (CLM) remains unclear. This study evaluates the optimal strategy for managing high-risk CLM. The subjects of this retrospective study were patients who underwent liver resection for initially resectable CLM between 2006 and 2021. High-risk status was defined by four or more metastases, a tumor size ≥ 5cm, or the presence of resectable extrahepatic disease. Among 363 eligible patients, 293 received NAC and 70 underwent upfront surgery. Propensity score matching (PSM) created balanced groups of 70 each. Among the patients who received NAC, seven did not undergo resection because they had disease progression. Intention-to-treat analysis revealed significantly longer median progression-free survival (PFS) (1.1 vs. 0.6years, p < 0.001) and overall survival (OS) (5.2 vs. 4.3years, p = 0.044) in the NAC group. Matched analysis confirmed superior PFS (1.2 vs. 0.6years, p = 0.004) and a favorable OS trend (5.4 vs. 4.3years, p = 0.164). Completion of the perioperative sequence of NAC, surgery, and AC was associated with the most favorable outcomes. Achieving a sequential strategy of NAC, surgery, and AC may improve the long-term survival of patients with high-risk CLM, supporting its potential as a standard treatment strategy.

The World Health Organization (WHO) 2019 classification of hepatocellular carcinoma (HCC) introduces new histological subtypes aiding morphomolecular classification. We aimed to reclassify and restage archival HCC following central pathology review and evaluate the frequency of new subtypes in a large European HCC cohort. All histological material of 100 curative liver resection specimens for HCC from 100 patients (80 male, median age 72, IQR: 61.5-76.5years, BCLC stage 0-C) operated from 2001 to 2018 was centrally reviewed. All cases were reclassified according to WHO 2019 and restaged according to TNM 2017 system. Thirty-five HCCs (35%) were classified into new subtypes: 15 macrotrabecular-massive (15%), 7 steatohepatitic (7%), 4 scirrhous (4%), 3 fibrolamellar (3%), 2 chromophobe (2%), 2 lymphocyte-rich (2%), 1 clear cell (1%), and 1 neutrophil-rich (1%). Histological grade changed in 45% HCCs (p < 0.001). TNM stage was modified from 1 to 2 in 22/100 HCCs (p < 0.001). The main histological pattern was solid (52%), pseudoglandular (17%), trabecular (16%), and macrotrabecular (15%). Microvascular invasion was detected in 64% HCCs. The non-neoplastic liver parenchyma showed steatosis (40%), steatohepatitis (19%), and/or chronic inflammation (71%). Fibrosis was staged as F0 35%, F1 17%, F2 13%, F3 11%, or F4 24%. Central histopathology review according to WHO 2019 and TNM 2017 modified histological grading in approximately half and staging in one quarter of resected HCCs, respectively, with clinical implications. One-third of HCCs were reclassified into new histological subtypes, some with known molecular background, prognostic and/or predictive impact, important for patient management.

Laparoscopic hemi-hepatectomy using the individual transection method (ITM) for tumors with hilar involvement is technically challenging due to the complex biliary anatomy. Indocyanine green (ICG) fluorescence cholangiography has the potential to improve intraoperative bile duct visualization; however, its clinical value in this setting has not been well established. We retrospectively reviewed 31 patients who underwent laparoscopic hemi-hepatectomy between July 2020 and September 2024. The Glissonean pedicle method (GPM) was used when secondary Glissonean branches were not involved, while the ITM was selected for tumors involving their confluence. ICG fluorescence cholangiography was employed in all cases treated with the ITM. Surgical outcomes and bile duct visualization were assessed using a three-grade Bile Duct Visualization Score (BDVS). Thirteen patients underwent laparoscopic hemi-hepatectomy using the ITM with ICG guidance. The median operative time in the ITM group was longer in comparison to the GPM group (425 vs. 334min, p = 0.026), while the median blood loss was similar between the groups (101 vs. 174mL, p = 0.968). Right hemi-hepatectomy was more frequently performed in the ITM group (n = 8 vs. n = 4), whereas left hemi-hepatectomy was predominant in the GPM group (n = 5 vs. n = 14; p = 0.027). According to the BDVS, 77% of ITM cases were classified as "clearly visible" (score 2). R0 resection was achieved in all cases. One case each of biliary stenosis and postoperative bile fistula was observed in the ITM group, both were managed non-surgically. No 90-day mortality occurred. ICG fluorescence cholangiography enabled reliable visualization of the hilar bile ducts and contributed to safe bile duct management in laparoscopic hemi-hepatectomy requiring application of the ITM. This technique provides useful support when performing laparoscopic liver resections in challenging cases.

Liver tumors in childhood are rare and associated with high treatment demands. Over the past decades substantial progress has been achieved through effective chemotherapies and improved surgical techniques as well as international collaborations. Nevertheless, the challenges for the surgical treatment remain high. In Germany additional specific difficulties arise in this context. To summarize the current evidence on the surgical management of pediatric liver tumors, to analyze the care structures in Germany and to develop perspectives for optimizing treatment. Narrative review of the current evidence, systematic analysis of the surgical results of previous hepatoblastoma studies, and evaluation of German care pathways in order to identify problems and perspectives. The improved prognosis of children with liver tumors (particularly hepatoblastoma) is mainly due to multimodal, risk-adapted treatment concepts and advances in surgical strategies. Because of the rarity of pediatric liver resections, pediatric liver tumor surgery in Germany is positioned at the intersection of pediatric, visceral and transplantation surgery. Surgically, strategies adapted to children are crucial to increase resection rates and avoid postoperative complications. A direct transfer of concepts from adult liver surgery carries substantial risks. In Germany the basic prerequisites are good but care can be further improved through better communication with reference structures, intelligent centralization approaches and investment in surgical training. Pediatric liver tumor surgery is associated with specific challenges due to the rarity and high demands. In Germany, strengthening multidisciplinary structures and communication as well as efficient centralization of treatment planning, can further improve patient safety and outcomes for children with liver tumors.

Patients with colorectal cancer (CRC) and malignant melanoma (MM) are at a significant risk of developing liver metastases. Despite surgical resection and systemic therapies, disease recurrence is common and long-term survival after relapse remains limited. Autologous tumor vaccines represent a promising immunotherapeutic approach by harnessing the immune system's capacity to elicit durable antitumor responses. A previously established melanoma immunotherapy protocol was used, combining low-dose cyclophosphamide with repeated intradermal injections of dinitrophenyl-modified autologous tumor cells admixed with Bacillus Calmette-Guérin as an immune adjuvant. Vaccine-induced delayed-type hypersensitivity (DTH) responses were prospectively monitored as a clinical marker of antitumor immune activation and treatment efficacy. This approach was adapted for use in non-melanoma solid tumors. Two patients with advanced disease - one with metastatic melanoma and one with metastatic CRC - experienced recurrent liver metastases following standard treatments and underwent vaccination using tumor cells derived from resected liver lesions. Initial vaccination failed to prevent disease recurrence in both patients. Treatment was subsequently individualized: a modified vaccine was generated for the patient with melanoma, whereas the patient with CRC was successfully treated with vaccine re-challenge. In both cases, the emergence of a positive DTH response was associated with complete clinical remission and durable disease control, with follow-up exceeding 20 years. Autologous tumor cell vaccines derived from liver metastases may represent a feasible therapeutic strategy capable of achieving durable remission and improved long-term outcomes in selected high-risk patients with metastatic disease.

Background and Aim: Adjuvant therapy after curative intent treatment for hepatocellular carcinoma (HCC) is a significant unmet need. The IMbrave050 study demonstrated improved recurrence-free survival (RFS) in patients with high-risk HCC receiving adjuvant atezolizumab and bevacizumab post-curative treatment compared to active surveillance. However, the IMbrave050 cohort was predominantly Asian, largely underwent surgical resection, and had chronic liver disease (CLD) mainly due to hepatitis B features that differ markedly from the Australian setting, where microwave ablation (MWA) is more common and hepatitis B-related CLD is less prevalent. Given these differences, this study aimed to explore the performance of the IMbrave050 risk criteria in an Australian population of patients with early-stage HCC undergoing curative treatment to determine if the criteria identified patients with a high risk of recurrence who may benefit from adjuvant treatment. Method: We performed a retrospective 5-year study of 50 patients with early-stage HCC undergoing MWA with curative intent or liver resection. Patients were stratified into high- and low-risk groups using the IMbrave050 criteria. The primary outcomes were RFS and overall survival (OS) in the high- and low-risk cohorts. Results: For patients who underwent liver resection, the 1-year RFS was 77.8% and 100% in high- and low-risk patients respectively (p = NS). In those who underwent MWA, the 1-year RFS was 89.5% in the high-risk cohort and 73.3% in the low-risk cohort (p = NS). OS at 1-year was 100% in all cohorts (p = NS). Conclusions: In this Western cohort receiving predominantly ablation as curative therapy the current high-risk criteria do not reliably distinguish between those with increased risk of early recurrence and those without. Criteria defining high-risk may need to be refined to better identify patients who may benefit from adjuvant therapy in this setting.

Acute liver injury and cardiovascular disease interact, forming a mutually exacerbating vicious cycle. However, the dynamic influence of hepatic vascular impedance on cardiac function has not been systematically elucidated. To address this gap, a closed-loop hemodynamic model based on lumped parameters was developed, encompassing the heart, liver, and the systemic arterial and venous circulation. This model was used to analyze how alterations in hepatic vascular impedance influence cardiac function and to provide a theoretical foundation for understanding liver-heart comorbidities. Healthy subjects served as the control group, while acute liver injury was simulated by proportionally increasing hepatic microvascular resistance. Changes in cardiovascular hemodynamic parameters were then systematically compared across conditions. As the severity of acute liver injury increases, the peak aortic flow and total cardiac output significantly decrease, with stroke volume reduced by approximately 17%. The left ventricular end-diastolic volume and stroke work are markedly diminished. Effective arterial elastance increases by about 20.7%, and the left ventricular ejection fraction decreases by approximately 4%. Furthermore, the change in hepatic arterial flow is considerably greater than that in portal vein flow. This closed-loop hemodynamic model reveals that acute liver injury leads to a reduction in preload and an increase in afterload, thereby causing abnormalities in both systolic and diastolic cardiac function. Global sensitivity analysis demonstrated that changes in presinusoidal vascular resistance serve as the major contributors to the resulting cardiac dysfunction. These findings provide a theoretical basis for understanding the interplay between liver and heart, and offer a feasible method for pre-assessing cardiovascular risk in patients prior to liver resection or transplantation.