Liver Surgery Research Articles

Soluble suppression of tumourigenicity 2 as a predictor of postoperative hepatic failure.

Posthepatectomy liver failure remains a potentially life-threatening complication after hepatectomy. Soluble suppression of tumourigenicity 2 is an injury-related biomarker. The aim of the study was to assess soluble suppression of tumourigenicity 2 elevation after hepatectomy and whether it can predict posthepatectomy liver failure. This was a single-centre retrospective study including all patients who underwent a liver resection between 2015 and 2019. Plasma concentrations of soluble suppression of tumourigenicity 2 were measured before surgery and at postoperative days 1, 2, 5 and 7. Posthepatectomy liver failure was defined according to the International Study Group of Liver Surgery and the morbidity rate was graded according to the Clavien-Dindo classification. A total of 173 patients were included (75 underwent major and 98 minor resection); plasma levels of soluble suppression of tumourigenicity 2 increased from 43.42 (range 18.69-119.96) pg/ml to 2622.23 (range 1354.18-4178.27) pg/ml on postoperative day 1 (P < 0.001). Postoperative day 1 soluble suppression of tumourigenicity 2 concentration accurately predicted posthepatectomy liver failure ≥ grade B (area under curve = 0.916, P < 0.001) and its outstanding performance was not affected by underlying disease, liver pathological status and extent of resection. The cut-off value, sensitivity, specificity, positive predictive value and negative predictive value of postoperative day 1 soluble suppression of tumourigenicity 2 in predicting posthepatectomy liver failure ≥ grade B were 3700, 92%, 85%, 64% and 97% respectively. Soluble suppression of tumourigenicity 2high patients more frequently experienced posthepatectomy liver failure ≥ grade B (64.3% (n = 36) versus 2.6% (n = 3)) and Clavien-Dindo IIIa higher morbidity rate (23.2% (n = 13) versus 5.1% (n = 6)) compared with soluble suppression of tumourigenicity 2low patients. Soluble suppression of tumourigenicity 2 may be a reliable predictor of posthepatectomy liver failure ≥ grade B as early as postoperative day 1 for patients undergoing liver resection. Its role in controlling hepatic injury/regeneration needs further investigation. Registration number: ChiCTR-OOC-15007210 (www.chictr.org.cn/).

Enhancing surgical planning for abdominal tumors in children through advanced 3D visualization techniques: a systematic review of future prospects.

Preoperative three-dimensional (3D) reconstruction using sectional imaging is increasingly used in challenging pediatric cases to aid in surgical planning. Many case series have described various teams' experiences, discussing feasibility and realism, while emphasizing the technological potential for children. Nonetheless, general knowledge on this topic remains limited compared to the broader research landscape. The aim of this review was to explore the current devices and new opportunities provided by preoperative Computed Tomography (CT) scans or Magnetic Resonance Imaging (MRI). A systematic review was conducted to screen pediatric cases of abdominal and pelvic tumors with preoperative 3D reconstruction published between 2000 and 2023. Surgical planning was facilitated through virtual reconstruction or 3D printing. Virtual reconstruction of complex tumors enables precise delineation of solid masses, formulation of dissection plans, and suggests dedicated vessel ligation, optimizing tissue preservation. Vascular mapping is particularly relevant for liver surgery, large neuroblastoma with imaging-defined risk factors (IDRFs), and tumors encasing major vessels, such as complex median retroperitoneal malignant masses. 3D printing can facilitate specific tissue preservation, now accessible with minimally invasive procedures like partial nephrectomy. The latest advancements enable neural plexus reconstruction to guide surgical nerve sparing, for example, hypogastric nerve modelling, typically adjacent to large pelvic tumors. New insights will soon incorporate nerve plexus images into anatomical segmentation reconstructions, facilitated by non-irradiating imaging modalities like MRI. Although not yet published in pediatric surgical procedures, the next anticipated advancement is augmented reality, enhancing real-time intraoperative guidance: the surgeon will use a robotic console overlaying functional and anatomical data onto a magnified surgical field, enhancing robotic precision in confined spaces.

Short-term and long-term results after minimally invasive liver resection for solitary small hepatocellular carcinoma : Analysis of 714 patients from the Italian group of minimally invasive liver surgery (IGoMILS) register

Short-term and long-term results after minimally invasive liver resection for solitary small hepatocellular carcinoma : Analysis of 714 patients from the Italian group of minimally invasive liver surgery (IGoMILS) register

Risk factors for delayed extubation after pediatric perineal anaplasty in patients less than 1 year of age: a retrospective study

BackgroundAnorectal malformation is a common congenital problem occurring in 1 in 5,000 births and has a spectrum of anatomical presentations, requiring individualized surgical treatments for normal growth. Delayed extubation or reintubation may result in a longer intensive care unit (ICU) stay and hospital stay, increased mortality, prolonged duration of mechanical ventilation, increased tracheostomy rate, and higher hospital costs. Extensive studies have focused on the role of risk factors in early extubation during major infant surgery such as Cardiac surgery, neurosurgery, and liver surgery. However, no study has mentioned the influencing factors of delayed extubation in neonates and infants undergoing angioplasty surgery.Materials and MethodsWe performed a retrospective study of neonates and infants who underwent anorectal malformation surgery between June 2018 and June 2022. The principal goal of this study was to observe the incidence of delayed extubation in pediatric anorectal malformation surgery. The secondary goals were to identify the factors associated with delayed extubation in these infants.ResultsWe collected data describing 123 patients who had anorectal malformations from 2019 to 2022. It shows that 74(60.2%) in the normal intubation group and 49(39.8%) in the longer extubation. In the final model, anesthesia methods were independently associated with delayed extubation (P < 0.05).ConclusionWe found that the anesthesia method was independently associated with early extubation in neonates and infants who accepted pediatric anorectal malformation surgery.

Validation of the IWATE Criteria in Robotic-Assisted Liver Resections.

Background/Objectives: The IWATE criteria are well-established as a helpful tool to preoperatively estimate the difficulty and perioperative outcome of laparoscopic liver resections. We evaluated the relationship between the IWATE criteria and the perioperative outcomes in robotic-assisted liver resections (RARLs). Methods: We retrospectively analyzed the data of 58 patients who underwent robotic-assisted liver surgery at our center between July 2019 and April 2023. The operative difficulty of every patient was graded according to the IWATE criteria and compared to the perioperative outcome. Results: The median operation time was 236.5 min (range 37-671 min), and the median length of stay was 6 days (range 3-37 min). The majority had no complications (65.5%; n = 38), 18 (31.0%) patients suffered from mild complications (CD ≤ 3A) and 2 patients (3.4%) suffered from relevant complications (CD ≥ 3B). We observed no deaths within 30 postoperative days. The surgery time, postoperative ICU stay and perioperative blood transfusions increased significantly with a higher difficulty level (p = < 0.001; p < 0.001; p = 0.016). The length of stay, conversion to open surgery (n = 2) and complication rate were not significantly linked to the resulting IWATE group. Conclusions: The IWATE criteria can be implemented in robotic-assisted liver surgery and can be helpful in preoperatively estimating the difficulty of robotic liver resections. Whether there is a "robotic effect" in minimally invasive liver resections has to be further clarified. The IWATE criteria can help to develop curricula for robotic training.

Augmented reality improving intraoperative navigation in minimally invasive liver surgery: an interplay between 3D reconstruction and indocyanine green.

Technology have helped surgeons to increase MILS feasibility, so that currently liver surgery evolution is strongly based on technological advances and the same trend is expected even further soon. Aim of the present technical report is to provide insights regarding the possible interplay between 3D reconstructions based on augmented reality and intraoperative navigation by indocyanine green fluorescence. Augmented reality methods based on reconstructions created through artificial intelligence interact synergistically. The better the understanding of the anatomy and characteristics of the lesion, the more accurate the preoperative planning may be scheduled. On the other hand, the better the intraoperative navigation, the more reproducible the preoperative planning becomes.

Abstract PO5-06-13: Impact of Therapy on Sites of Metastases in Triple Negative Breast Cancer

Abstract Background: Metastatic triple negative breast cancer (TNBC) is a diverse disease with the propensity to spread to visceral organs and the central nervous system (CNS). While systemic chemotherapy is commonly used, there is a growing utilization of immune checkpoint inhibitors (ICI) and antibody drug conjugates (ADC). However, few studies have examined the impact of specific therapies on individual metastatic sites, limiting clinical guidance for solitary metastases. Objective: This study aimed to evaluate the efficacy of various systemic therapies in TNBC patients with lung, liver, and CNS metastases. Methods: We analyzed data from the Dallas Metastatic Breast Cancer Study, a retrospective cohort study that includes all patients with metastatic breast cancer treated at a single academic medical center and identified 52 TNBC patients with visceral and CNS metastases diagnosed between 2009 and 2021. We correlated the site of metastasis with and treatment response, which was assessed based on imaging findings using RECIST 1.1 criteria. Results and Discussion: The median age at diagnosis of visceral metastatic disease was 52 years. Of the patients, 60% presented with de novo metastatic disease, while 40% experienced disease recurrence. The most prevalent metastatic sites were the lung (n=28), CNS (n=28), and liver (n=9). Among patients with detectable circulating tumor DNA, the most prevalent gene mutations in lung metastases were TP53 (36%), PTEN (13%), and PIK3R1 (10%). In liver metastases, TP53 (53%) and BRCA1 (15%) mutations were the most frequently observed. Similarly, in CNS metastases, TP53 (40%) and BRCA1 (13%) mutations were again most frequently detected. The notable frequency of TP53 mutations indicates the necessity for further investigations to explore potential differences in treatment approaches for patients with these mutations. The median overall survival (OS) was 14.43 months ±15.53, with the longest survival observed in patients with lung metastases (15 months), followed by liver metastases (6 months) and CNS metastases (5 months). Patients with involvement of a single visceral or CNS site had a mean OS of 15.80±18.19 months, whereas those with two sites of involvement had a mean OS of 13.08±10.18 months. Patients with metastases in all three sites had a mean OS of 8.33±8.50 months. Treatment modalities varied among patients. For liver metastases, chemotherapy (n=6), ICI (n=2), ADC (n=1), radiation therapy (n=2), and surgery (n=1) were administered. Lung metastases were treated with chemotherapy (n=26), ICI (n=4), ADC (n=5), radiation therapy (n=4), and surgery (n=1). CNS metastases were managed with chemotherapy (n=14), ICI (n=2), ADC (n=1), radiation therapy (n=21), and surgery (n=4). Systemic therapy for liver metastases resulted in stable disease (75%) and progressive disease (25%). In lung metastases, it led to stable disease (56%), partial response (23%), complete response (13%), and progressive disease (8%). CNS metastases treated with systemic therapy demonstrated stable disease (86%) and progressive disease (14%). The most commonly used systemic therapy was paclitaxel. Immunotherapy achieved a partial response (60%), stable disease (20%), and progressive disease (20%) in metastatic lesions. Treatment with ADCs resulted in stable disease (43%), partial response (29%), and progressive disease (29%). Compared to lung metastases, liver and CNS metastases exhibited lower response rates and overall survival. CNS metastases were less likely to receive systemic therapies, indicating a need for improvement. These findings highlight the importance of personalized treatment strategies tailored to individual metastatic sites in TNBC. Citation Format: Hannah Chang, Pallavi Dev, Luise Froessl, Shao-Po Huang, Christine Hodgdon, Julia Maues, Isaac Chan. Impact of Therapy on Sites of Metastases in Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-13.

Quercetin, a natural flavonoid, protects against hepatic ischemia–reperfusion injury via inhibiting Caspase-8/ASC dependent macrophage pyroptosis

IntroductionHepatic ischemia–reperfusion injury (IRI) is an inevitable adverse event following liver surgery, leading to liver damage and potential organ failure. Despite advancements, effective interventions for hepatic IRI remain elusive, posing a significant clinical challenge. The innate immune response significantly contributes to the pathogenesis of hepatic IRI by promoting an inflammatory cytotoxic cycle. We have reported that blocking GSDMD-induced pyroptosis in innate immunity cells protected hepatic IRI from inflammatory injury. However, the search for effective pyroptosis inhibitors continues. ObjectivesThis study aims to evaluate whether quercetin, a natural flavonoid, can inhibit GSDMD-induced pyroptosis and mitigate hepatic IRI. MethodsWe established the hepatic IRI murine model and cellular pyroptosis model to evaluate the efficacy of quercetin. ResultsQuercetin effectively alleviated hepatic IRI-induced tissue necrosis and inflammation. We found that during hepatic IRI, the cleavage of GSDMD occurred in hepatic macrophages, but not in other non-parenchymal cells. Quercetin inhibited the cleavage of GSDMD in macrophages. Moreover, we found that quercetin blocked the ASC assembly to inhibit the formation of NLRP3 inflammasomes and AIM2 inflammasomes, suppressing macrophage pyroptosis. Co-immunoprecipitation experiments confirmed that quercetin inhibited the interaction between ASC and Caspase-8, which is the mechanism of ASC complex and inflammasome formation. Overexpression of Caspase-8 abolished the anti-pyroptosis effect of quercetin in NLRP3 and AIM2 inflammasome signaling. Furthermore, we found that the hepatoprotective activity of quercetin was reduced in myelocytic GSDMD-deficient mice. ConclusionOur findings suggest that quercetin has beneficial effects on hepatic IRI. Quercetin could attenuate hepatic IRI and target inhibition of macrophage pyroptosis via blocking Caspase-8/ASC interaction. We recommend that quercetin might serve as a targeted approach for the prevention and personalized treatment of hepatic IRI in perioperative patients.

EGFR-mediated crosstalk between vascular endothelial cells and hepatocytes promotes Piezo1-dependent liver regeneration

Hepatocyte proliferation is essential for recovering liver function after injury. In liver surgery, the mechanical stimulation induced by hemodynamic changes triggers vascular endothelial cells (VECs) to secrete large amounts of cytokines that enhance hepatocyte proliferation and play a pivotal role in liver regeneration. Piezo1, a critical mechanosensory ion channel, can detect and convert mechanical forces into chemical signals, importing external stimuli into cells and triggering downstream biological effects. However, the precise role of Piezo1 in VECs, especially in terms of mediating liver regeneration, remains unclear. Here, we report on a potential mechanism by which early changes in hepatic portal hemodynamics activate Piezo1 in VECs to promote hepatocyte proliferation during the process of liver regeneration induced by portal vein ligation in rats. In this liver regeneration model, hepatocyte proliferation is mainly distributed in zone 1 and zone 2 of liver lobules at 24–48 h after surgery, while only a small number of Ki67-positive hepatocytes were observed in zone 3. Activation of Piezo1 promotes increased secretion of epiregulin and amphiregulin from VECs via the PKC/ERK1/2 axis, further activating epidermal growth factor receptor (EGFR) and ERK1/2 signals in hepatocytes and promoting proliferation. In addition, cytokines secreted by Piezo1-activated VECs can induce hepatocytes to undergo epithelial–mesenchymal transition. In the liver lobules, the expression of EGFR in hepatocytes of zone 1 and zone 2 is significantly higher than that in zone 3. The EGFR inhibitor gefitinib inhibits liver regeneration by suppressing the proliferation of hepatocytes in the middle zone. Thus, activation of Piezo1 in VECs promotes hepatocyte proliferation, suggesting mechanical stimulation regulates hepatocyte proliferation in zone 1 and zone 2 during portal vein ligation-induced liver regeneration. These data provide a theoretical basis for the regulation of liver regeneration through chemical signals mediated by mechanical stimulation.

Effects of Omega-3 Polyunsaturated Fatty Acids, Docosahexaenoic Acid and Eicosapentaenoic Acid, on Post-Surgical Complications in Surgical Trauma Patients: Mechanisms, Nutrition, and Challenges.

This paper aims to provide an in-depth review of the specific outcomes associated with omega-3 polyunsaturated fatty acids (PUFAs), focusing on their purported effects on post-surgical complications in trauma patients. A comprehensive investigation of omega-3 polyunsaturated fatty acids was conducted until February 2023 using the PubMed database. Surgical trauma is characterized by a disruption in immune response post surgery, known to induce systemic inflammation. Omega-3 PUFAs are believed to offer potential improvements in multiple post-surgical complications because of their anti-inflammatory and antioxidant properties. Inconsistent findings have emerged in the context of cardiac surgeries, with the route of administration playing a mediating role in these outcomes. The effects of omega-3 PUFAs on post-operative atrial fibrillation have exhibited variability across various studies. Omega-3 PUFAs have demonstrated positive effects in liver surgery outcomes and in patients with acute respiratory distress syndrome. Omega-3 is suggested to offer potential benefits, particularly in the perioperative care of patients undergoing traumatic procedures. Incorporating omega-3 in such cases is hypothesized to contribute to a reduction in certain surgical outcomes, such as hospitalization duration and length of stay in the intensive care unit. Therefore, comprehensive assessments of adverse effects can aid in identifying the presence of subtle or inconspicuous side effects associated with omega-3.

Machine learning in liver surgery: Benefits and pitfalls

The application of machine learning (ML) algorithms in various fields of hepatology is an issue of interest. However, we must be cautious with the results. In this letter, based on a published ML prediction model for acute kidney injury after liver surgery, we discuss some limitations of ML models and how they may be addressed in the future. Although the future faces significant challenges, it also holds a great potential.

Giant liver cyst associated with cholelithiasis: literature review and state of art

Liver lesions subject to laparoscopic resection are one of the frontiers conquered in surgery today. Even when dealing with surgery, which is often complex, the increase in demand from patients has increased, bringing more and more learning and dexterity to surgery teams with the increasing development of technology. To analytically evaluate the method, based on the most recent publications in the literature, with possible indications and reporting a recently successfully operated case, highlighting the safety, results and fundamental technical aspects. The relevant works from the last 15 years were identified and analyzed in the LILACS and PUBMED databases until August 2023, using the descriptors “ liver resection ”, “ laparoscopic surgery ” and “ liver surgery ”. We don't We found prospective and double-blind studies in the databases, with available data coming from case series, case-control studies and some multicenter studies and meta-analyses. Laparoscopic hepatectomy is a safe surgery and is very standardized in execution, even for major liver resections, with a low morbidity and mortality rate. As an oncological surgical method, it is gaining more and more space without compromising oncological radicality and with advantages for patients. with specific liver diseases. Benign lesions are the best indicated and performed, especially adenoma and cystic lesions, which in the hands of experienced teams have very good results and videolaparoscopic surgery can be considered today as standard treatment.

Impact of blood salvage therapy during oncologic liver surgeries on allogenic transfusion events, survival, and recurrence, an ambidirectional cohort study.

The use of autologous blood transfusions in oncologic surgeries is somewhat controversial due to the potential risk of disease dissemination through the salvage process. On the other hand, autologous blood transfusion can prevent the potential negative effects of allogenic blood transfusions and reduce use of valuable resources. This study included 106 adult patients who underwent oncologic liver surgery at our institution between December 2015 and June 2019. The patients were divided into two groups: the Cell Saver® group (operated between January 2018 and June 2019) and the control group (operated between December 2015 and December 2017). The Cell Saver® device was present in the operating room for the Cell Saver® group, and blood was re-transfused if a certain amount of blood loss occurred. Data analysis focused on outcomes such as blood transfusion requirements, overall survival, recurrence-free survival, hemoglobin levels, hospital stay, and complications. Patient records provided relevant information on demographics, surgery details, pathology, and outcomes for both groups. Autologous blood transfusion was found to reduce the amount of blood units needed (4.0 units (control group) versus 0.4 units (Cell Saver® group) P=0.029. Kaplan-Meier curves showed no difference for both overall survival 471.6 days (Cell Saver® group) versus 468.3 days (control group) (P=0.219) and 488.9 days (Cell Saver® group) versus 487.2 days (control group) (P=0.993) and disease-free survival (P=0.553) and (P=0.735) for primary hepatic tumours and hepatic metastasis respectively between the Cell Saver® and control groups. Overall survival regardless of the type of tumour was similar to the control group (485.4d vs. 481.9d) (P=0.503). Survival was significantly lower for minor hepatectomies (516.0d vs. 517.4d) (P=0.050) in the Cell Saver® group, major hepatectomies showed no difference in overall survival (470.2d vs. 466.4d) (P=0.868). No impact on disease recurrence was found between patients who received autologous blood transfusions versus those who did not. The use of Cell Saver® should not be avoided in oncologic surgeries of the liver. Use of Cell Saver® for major hepatectomies might be more beneficial as OS was significantly lower for the Cell Saver® group for patients who underwent minor hepactomies. Further research is needed to explain this conflicting result. Nonetheless, the use of Cell Saver® in autologous blood transfusions can reduce the use of valuable resources and the risks associated with allogenic blood transfusions.

Robotic Left Hepatectomy with En Bloc Biliary Resection and Roux-en-Y Hepaticojejunostomy: A Technique of Portal Venous Tangential Vascular Reconstruction.

Robotic technology is increasingly utilized in perihilar cholangiocarcinoma treatments, requiring expertise in minimally invasive liver surgeries and biliary reconstructions. These resections often involve vascular and multiple sectoral bile duct reconstructions. Minimally invasive vascular repairs are now emerging with promising outcomes, potentially altering criteria for selecting minimally invasive hepatobiliary tumor resections. In this multimedia article, we describe our technique of robotic portal venous tangential primary reconstruction with right sectoral bile duct unification ductoplasty for the treatment of perihilar cholangiocarcinoma using the robotic approach. The robotic technique was chosen in this operation with preoperative anticipation of needing vascular resection and reconstruction due to left portal vein tumor involvement. Additionally, a Roux-en-Y hepaticojejunostomy to the right anterior and posterior sectoral duct was planned for biliary reconstruction. Proximal and distal vascular control of the portal vein bifurcation was obtained by placing vascular bulldog clamps across the main and right portal veins. Once an R0 vascular margin was obtained on the left portal vein, portal bifurcation was tangentially repaired. Perfusion to the liver was then restored, and left hemihepatectomy with enbloc extrahepatic biliary resection was carried out, followed by Roux-en-Y hepaticojejunostomy reconstruction to the right anterior and posterior sectoral bile ducts, as a single anastomosis. The operation was uneventful without vascular or biliary complications. Robotic unification ductoplasty circumvented the need for multiple anastomoses. The robotic approach for left-sided perihilar cholangiocarcinoma resections, requiring precise biliovascular management, is safe, feasible, and efficient. This method demonstrates the potential of robotic techniques as an alternative to traditional open surgery.

From morbidity reduction to cost-effectiveness: Enhanced recovery after surgery (ERAS) society recommendations in minimal invasive liver surgery

PurposeMinimal-invasive liver surgery (MILS) reduces surgical trauma and is associated with fewer postoperative complications. To amplify these benefits, perioperative multimodal concepts like Enhanced Recovery after Surgery (ERAS), can play a crucial role. We aimed to evaluate the cost-effectiveness for MILS in an ERAS program, considering the necessary additional workforce and associated expenses.MethodsA prospective observational study comparing surgical approach in patients within an ERAS program compared to standard care from 2018—2022 at the Charité – Universitätsmedizin Berlin. Cost data were provided by the medical controlling office. ERAS items were applied according to the ERAS society recommendations.Results537 patients underwent liver surgery (46% laparoscopic, 26% robotic assisted, 28% open surgery) and 487 were managed by the ERAS protocol. Implementation of ERAS reduced overall postoperative complications in the MILS group (18% vs. 32%, p = 0.048). Complications greater than Clavien-Dindo grade II incurred the highest costs (€ 31,093) compared to minor (€ 17,510) and no complications (€13,893; p < 0.001). In the event of major complications, profit margins were reduced by a median of € 6,640.ConclusionsEmbracing the ERAS society recommendations in liver surgery leads to a significant reduction of complications. This outcome justifies the higher cost associated with a well-structured ERAS protocol, as it effectively offsets the expenses of complications.

Impact of enhanced recovery program implementation on postoperative outcomes after liver surgery: a monocentric retrospective study.

It is still unclear whether enhanced recovery programs (ERPs) reduce postoperative morbidity after liver surgery. This study investigated the effect on liver surgery outcomes of labeling as a reference center for ERP. Perioperative data from 75 consecutive patients who underwent hepatectomy in our institution after implementation and labeling of our ERP were retrospectively compared to 75 patients managed before ERP. Length of hospital stay, postoperative complications, and adherence to protocol were examined. Patient demographics, comorbidities, and intraoperative data were similar in the two groups. Our ERP resulted in shorter length of stay (3 days [1-6] vs. 4 days [2-7.5], p = 0.03) and fewer postoperative complications (24% vs. 45.3%, p = 0.0067). This reduction in postoperative morbidity can be attributed exclusively to a lower rate of minor complications (Clavien-dindo grade < IIIa), and in particular to a lower rate of postoperative ileus, after labeling. (5.3% vs. 25.3%, p = 0.0019). Other medical and surgical complications were not significantly reduced. Adherence to protocol improved after labeling (17 [16-18] vs. 14 [13-16] items, p < 0.001). The application of a labeled enhanced recovery program for liver surgery was associated with a significant shortening of hospital stay and a halving of postoperative morbidity, mainly ileus.

Robotic versus Laparoscopic Liver Resections for Colorectal Metastases: A Systematic Review and Meta-Analysis.

Colorectal cancer is the third most common cancer worldwide, and the liver is the most common localization of metastatic disease. The incidence of minimally invasive liver surgery is increasing, and robotic surgery (RLR) is believed to overcome some limitations of a laparoscopic approach (LRL). We performed a systematic review and meta-analysis of operative and short-term oncologic outcomes of the laparoscopic versus robotic-assisted liver resection for colorectal liver metastases. An online search of PubMed, Embase, Scopus, and the Cochrane databases was performed. Eight studies involving 3210 patients were considered eligible for the meta-analysis. In the LRL group, a higher conversion to open rate (12.4%) was observed compared to the RLR (6.7%; p = <0.001). 30-day mortality was 0.7% for the LRL group compared to 0.5% for the RLR group (p = 0.76). Mortality in longer periods among LLR and RLR amounted to 18.2% vs. 8.0% for 1-year mortality (p = 0.07), 34.1% vs. 26.7% for 2-year mortality (p = 0.13), and 52.3% vs. 48.3% for 3-year mortality (p = 0.46). The length of hospital stay was 5.6 ± 2.5 vs. 5.8 ± 2.1 days, respectively (p = 0.47). There were no significant differences between the incidence of individual complications in the LRL and RLR groups (p = 0.78). Laparoscopic or robotic approaches for colorectal liver metastases are comparable in terms of safety and effectiveness. There are significant advantages to robotic surgery, although there is still no long-term evidence concerning overall survival, and the number of patients operated on using RLR remains small.

ICG-Fluorescence Imaging for Margin Assessment During Minimally Invasive Colorectal Liver Metastasis Resection

Unintended tumor-positive resection margins occur frequently during minimally invasive surgery for colorectal liver metastases and potentially negatively influence oncologic outcomes. To assess whether indocyanine green (ICG)-fluorescence-guided surgery is associated with achieving a higher radical resection rate in minimally invasive colorectal liver metastasis surgery and to assess the accuracy of ICG fluorescence for predicting the resection margin status. The MIMIC (Minimally Invasive, Indocyanine-Guided Metastasectomy in Patients With Colorectal Liver Metastases) trial was designed as a prospective single-arm multicenter cohort study in 8 Dutch liver surgery centers. Patients were scheduled to undergo minimally invasive (laparoscopic or robot-assisted) resections of colorectal liver metastases between September 1, 2018, and June 30, 2021. All patients received a single intravenous bolus of 10 mg of ICG 24 hours prior to surgery. During surgery, ICG-fluorescence imaging was used as an adjunct to ultrasonography and regular laparoscopy to guide and assess the resection margin in real time. The ICG-fluorescence imaging was performed during and after liver parenchymal transection to enable real-time assessment of the tumor margin. Absence of ICG fluorescence was favorable both during transection and in the tumor bed directly after resection. The primary outcome measure was the radical (R0) resection rate, defined by the percentage of colorectal liver metastases resected with at least a 1 mm distance between the tumor and resection plane. Secondary outcomes were the accuracy of ICG fluorescence in detecting margin-positive (R1; <1 mm margin) resections and the change in surgical management. In total, 225 patients were enrolled, of whom 201 (116 [57.7%] male; median age, 65 [IQR, 57-72] years) with 316 histologically proven colorectal liver metastases were included in the final analysis. The overall R0 resection rate was 92.4%. Re-resection of ICG-fluorescent tissue in the resection cavity was associated with a 5.0% increase in the R0 percentage (from 87.4% to 92.4%; P < .001). The sensitivity and specificity for real-time resection margin assessment were 60% and 90%, respectively (area under the receiver operating characteristic curve, 0.751; 95% CI, 0.668-0.833), with a positive predictive value of 54% and a negative predictive value of 92%. After training and proctoring of the first procedures, participating centers that were new to the technique had a comparable false-positive rate for predicting R1 resections during the first 10 procedures (odds ratio, 1.36; 95% CI, 0.44-4.24). The ICG-fluorescence imaging was associated with changes in intraoperative surgical management in 56 (27.9%) of the patients. In this multicenter prospective cohort study, ICG-fluorescence imaging was associated with an increased rate of tumor margin-negative resection and changes in surgical management in more than one-quarter of the patients. The absence of ICG fluorescence during liver parenchymal transection predicted an R0 resection with 92% accuracy. These results suggest that use of ICG fluorescence may provide real-time feedback of the tumor margin and a higher rate of complete oncologic resection.

Risk model for morbidity and mortality following liver surgery based on a national Japanese database.

We evaluated the morbidity and mortality associated with liver surgery in Japan and developed a risk model for liver resection using information from a national database. We retrospectively reviewed 73 861 Japanese patients who underwent hepatectomy between 2014 and 2019, using information from the National Clinical Database (NCD) registrations. The primary endpoints were 30 days and in-hospital mortality, and the secondary endpoints were postoperative complications. Logistic regression risk models for postoperative morbidity and mortality after hepatectomy were constructed based on preoperative clinical parameters and types of liver resection, and validated using a bootstrapping method. The 30-day and in-hospital mortality rates were 0.9% and 1.7%, respectively. Trisectionectomy, hepatectomy for gallbladder cancer, hepatectomy for perihilar cholangiocarcinoma, and poor activities of daily living were statistically significant risk factors with high odds ratios for both postoperative morbidity and mortality. Internal validations indicated that the c-indices for 30-day and in-hospital mortality were 0.824 and 0.839, respectively. We developed a risk model for liver resection by using a national surgical database that can predict morbidity and mortality based on preoperative factors.

Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis

BackgroundLiver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family.MethodsThe expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep−/−. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS).ResultsExcessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis.ConclusionsThis study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.