Major Hepatic Surgery Research Articles

Pharmaceutical Interventions for the Management of Hemorrhagic Shock in Hepatic Surgery: An Experimental Swine Model Outcome.

Introduction During abdominal trauma or major hepatic surgery, the liver can be subjected to hypoxic conditions due to hemorrhage, leading to various degrees of ischemic injury to hepatocytes. Hemorrhagic shock, a critical and life-threatening condition, often complicates hepatic surgery due to massive blood loss, resulting in inadequate tissue perfusion and oxygenation. The challenge in managing hemorrhagic shock in hepatic surgery is heightened by the liver's unique blood supply and its crucial role in coagulation. Effective treatment requires a multifaceted approach, including surgical intervention, blood transfusions, and pharmaceutical therapy to stabilize hemodynamics and promote coagulation. Additionally, reperfusion of the liver after resuscitation can cause severe injury through inflammatory and oxidative pathways, potentially leading to multiple organ dysfunction. This study examines the effectiveness of combining standard fluid therapy with antioxidants (bucillamine and valproic acid) in mitigating oxidative stress and reducing hepatocyte damage in the context of hemorrhagic shock. Method Thirty male swine were randomly divided into four groups as follows: Group A (n=6/control group), Group B (n=8), Group C (n=8), and Group D (n=8). A resection of the left liver lobe was performed, followed by the controlled loss of a specific volume of blood until the mean arterial pressure dropped to between 30 and 40 mmHg. The animals were maintained in this state of hypovolemic shock for 50 minutes, followed by IV administration of fluids. Additionally, pharmaceutical agents were administered to Groups B (bucillamine), C (valproic acid), and D (combination of bucillamine and valproic acid). The experiment lasted six hours in total. Results The study showed that animals treated with pharmaceutical agents like bucillamine and valproic acid and their combination demonstrated significantly reduced serum levels of protein carbonyls (PCs) and thiobarbituric acid reactive substances (TBARS) compared to the control group. Furthermore, histological evaluation of liver tissues revealed that treated animals showed reduced histopathological signs of injury, suggesting that the pharmaceutical agents not only lowered biochemical markers of oxidative stress but also provided a protective effect against liver damage in the context of hemorrhagic shock. Conclusion These findings suggest that incorporating antioxidant therapy into resuscitation protocols may offer substantial benefits in mitigating hepatic damage associated with hemorrhagic shock. This approach could potentially improve outcomes in clinical settings where oxidative stress plays a critical role in injury progression by better understanding the pathophysiology of this complex and dynamic process.

Restrictive versus Decision Support Guided Fluid Therapy during Major Hepatic Resection Surgery: A Randomized Controlled Trial.

Fluid therapy during major hepatic resection aims at minimizing fluids during the dissection phase to reduce central venous pressure, retrograde liver blood flow, and venous bleeding. This strategy, however, may lead to hyperlactatemia. The Acumen assisted fluid management system uses novel decision support software, the algorithm of which helps clinicians optimize fluid therapy. The study tested the hypothesis that using this decision support system could decrease arterial lactate at the end of major hepatic resection when compared to a more restrictive fluid strategy. This two-arm, prospective, randomized controlled, assessor- and patient-blinded superiority study included consecutive patients undergoing major liver surgery equipped with an arterial catheter linked to an uncalibrated stroke volume monitor. In the decision support group, fluid therapy was guided throughout the entire procedure using the assisted fluid management software. In the restrictive fluid group, clinicians were recommended to restrict fluid infusion to 1 to 2 ml · kg-1 · h-1 until the completion of hepatectomy. They then administered fluids based on advanced hemodynamic variables. Noradrenaline was titrated in all patients to maintain a mean arterial pressure greater than 65 mmHg. The primary outcome was arterial lactate level upon completion of surgery (i.e., skin closure). A total of 90 patients were enrolled over a 7-month period. The primary outcome was lower in the decision support group than in the restrictive group (median [quartile 1 to quartile 3], 2.5 [1.9 to 3.7] mmol · l-1vs. 4.6 [3.1 to 5.4] mmol · l-1; median difference, -2.1; 95% CI, -2.7 to -1.2; P < 0.001). Among secondary exploratory outcomes, there was no difference in blood loss (median [quartile 1 to quartile 3], 450 [300 to 600] ml vs. 500 [300 to 800] ml; P = 0.727), although central venous pressure was higher in the decision support group (mean ± SD of 7.7 ± 2.0 mmHg vs. 6.6 ± 1.1 mmHg; P < 0.002). Patients managed using a clinical decision support system to guide fluid administration during major hepatic resection had a lower arterial lactate concentration at the end of surgery when compared to a more restrictive fluid strategy. Future trials are necessary to make conclusive recommendations that will change clinical practice.

Comprehensive analysis of cuproptosis-related genes involved in immune infiltration and their use in the diagnosis of hepatic ischemia‒reperfusion injury: an experimental Study.

Hepatic ischemia reperfusion injury (HIRI) is a common injury not only during liver transplantation but also during major hepatic surgery. HIRI causes severe complications and affects the prognosis and survival of patients. Cuproptosis, a newly identified form of cell death, plays an important role in a variety of illnesses. However, its role in HIRI remains unknown. The GSE151648 dataset was mined from the Gene Expression Omnibus (GEO) database, and differences were analyzed for intersections. Based on the differentially expressed genes (DEGs), functional annotation, differentially expressed cuproptosis-related genes (DE-CRGs) identification and lasso logistic regression were conducted. Correlation analysis of DE-CRGs and immune infiltration was further conducted, and DE-CRGs were applied to construct an HIRI diagnostic model. The hierarchical clustering method was used to classify the specimens of HIRI, and functional annotation was conducted to verify the accuracy of these DE-CRGs in predicting HIRI progression. The GSE14951 microarray dataset and GSE171539 single-cell sequencing dataset were chosen as validation datasets. At the same time, the significance of DE-CRGs was verified using a mouse model of HIRI with cuproptosis inhibitors and inducers. Finally, a network of transcription-factor-DE-CRGs and miRNA-DE-CRGs was constructed to reveal the regulation mechanisms. And potential drugs for DE-CRGs were predicted using Drug Gene Interaction Database (DGIdb). Overall, 2390 DEGs and 19 DE-CRGs were identified. Through machine learning algorithms, 8 featured DE-CRGs (GNL3, ALAS1, TSC22D2, KLF5, GTF2B, DNTTIP2, SLFN11 and HNRNPU) were screened, and 2 cuproptosis-related subclusters were defined. Based on the 8 DE-CRGs obtained from the HIRI model (AUC=0.97), the nomogram model demonstrated accuracy in predicting HIRI. Eight DE-CRGs were highly expressed in HIRI samples and were negatively related to immune cell infiltration. A higher level of immune infiltration and expression of CRG group B was found in the HIRI population. Differences in cell death and immune regulation were found between the 2 groups. The diagnostic value of the 8 DE-CRGs was confirmed in the validation of two datasets. The identification of 7 DE-CRGs (SLFN11 excluded) by HIRI animal model experiments was also confirmed. Using hTFtarget, miRWalk and DGIDB database, we predicted that 17 transcription factors, 192 miRNAs and 10 drugs might interact with the DE-CRGs. This study shows that cuproptosis may occur in HIRI and is correlated with immune infiltration. Additionally, a cuproptosis-related predictive model was constructed for studying the causes of HIRI and developing targeted treatment options for HIRI.

Dose adjusted prophylactic lovenox dosing in hepatic surgery

Background: Recommended prophylactic doses of enoxaparin are often associated with sub-prophylactic anti-Factor Xa (anti-Xa) levels. This study examines the safety and efficacy of using anti-Xa levels to achieve prophylactic enoxaparin levels in patients who underwent major hepatic surgery.

Concurrent major hepatic resection with primary colorectal cancer increases risk of organ space infections.

Patients with colorectal cancer frequently present with liver metastases requiring either concurrent colon and liver resection or staged resection for curative therapy. The goal of this study is to determine if synchronous resection increases risk of perioperative adverse outcomes such as surgical site infections (SSIs). We conducted a cross-sectional retrospective analysis of the targeted hepatectomy NSQIP database from 2015 to 2019. The primary outcome was surgical site infections stratified into superficial, deep, organ space, and wound dehiscence. We performed univariate followed by a multivariate logistic regression to determine if there were higher odds of SSIs in patients undergoing hepatic resection concurrently with primary colorectal resection. Additionally, we performed stratified analyses by size of hepatic resections (partial, total left, total right, and trisegmentectomy). Of the 7,445 patients included in the study, 431(5.8%) underwent synchronous resection and 7,014 metachronous resection. On average, synchronous resections prolonged surgery by 62min. There was no difference in superficial and deep SSIs between the groups; however, there was a significant difference in organ space SSIs. Patients undergoing synchronous resection had 1.51 times the odds of developing an organ space SSI (OR 1.51, 95%CI 1.10, 2.17, p = 0.04) compared to patients with metachronous resection on multivariate analysis. Patients undergoing a total right hepatectomy concurrently with a colorectal resection had 2.30 times the odds of developing an organ space SSI (OR 2.30, 95%CI 1.20, 6.86, p = 0.010). Prior studies demonstrated that synchronous resections are safe in properly selected patients with no difference in long-term outcomes. Few studies have explored immediate perioperative outcomes between the two approaches. After controlling for confounders, we demonstrate that synchronous resection with major hepatic surgery increases the risk of organ space SSIs. Future studies should elucidate the precise source of organ space SSIs in order to decrease the risk of this adverse outcome.

Integrative analyses of genes related to liver ischemia reperfusion injury

BackgroundLiver ischemia reperfusion injury (LIRI) is not only a common injury during liver transplantation and major hepatic surgery, but also one of the primary factors that affect the outcome of postoperative diseases. However, there are still no reliable ways to tackle the problem. Our study aimed to find some characteristic genes associated with immune infiltration that affect LIRI, which can provide some insights for future research in the future. Therefore, it is essential for the treatment of LIRI, the elucidation of the mechanisms of LIRI, and exploring the potential biomarkers. Efficient microarray and bioinformatics analyses can promote the understanding of the molecular mechanisms of disease occurrence and development.MethodData from GSE151648 were downloaded from GEO data sets, and we performed a comprehensive analysis of the differential expression, biological functions and interactions of LIRI-associated genes. Then we performed Gene ontology (GO) analysis and Kyotoencydlopedia of genes and genomes (KEGG) enrichment analysis of DEGs. At last, we performed a protein-protein interaction network to screen out hub genes.ResultsA total of 161 differentially expressed genes (DEGs) were identified. GO analysis results revealed that the changes in the modules were mostly enriched in the neutrophil degranulation, neutrophil activation involved in immune response, and neutrophil mediated immunity. KEGG enrichment analysis of DEGs demonstrated that LIRI mainly involved the cytokine-cytokine receptor interaction. Our data indicated that macrophages and neutrophils are closely related to LIRI. 9 hub genes were screened out in the protein-protein interaction network.ConclusionsIn summary, our data indicated that neutrophil degranulation, neutrophil activation involved in immune response, neutrophil mediated immunity and cytokine-cytokine receptor interaction may play a key role in LIRI, HRH1, LRP2, P2RY6, PKD1L1, SLC8A3 and TNFRSF8, which were identified as potential biomarkers in the occurrence and development of LIRI. However, further studies are needed to validate these findings and explore the molecular mechanism of these biomarkers in LIRI.

Importance of computed tomography muscle quality and continuous versus cut-off-based sarcopenia detection in major hepatic surgery.

BackgroundThe role of the computed tomography (CT)-derived skeletal muscle index (SMI) as a parameter of muscle quantity on the outcome after major liver resection remains contradictory and that of the muscle radiodensity attenuation (MRA) as a parameter of muscle quality has not been sufficiently evaluated. This observational study aimed to investigate the influence of metric SMI and MRA values and cut-off-based CT sarcopenia detection on liver-surgery specific complications measured by the new FABIB (liver failure, ascites, biliary leakage, infection, bleeding) score and survival after hemihepatectomy.MethodsA total of 183 patients with major hepatectomy were retrospectively included. The SMI and MRA were determined from the abdominal muscle area of preoperative CT scans. Patients were classified as sarcopenic by the SMI and MRA cut-off values of Prado et al., Martin et al., and van der Werf et al. Postoperative complications were documented according to the Clavien-Dindo classification and FABIB score. The relation of the continuous, non-categoric SMI and MRA values and of the cut-off-based sarcopenia detection to the postoperative complications and survival was analyzed by multivariable linear, logistic, and Cox proportional hazards regression.ResultsA higher MRA was associated with less severe postoperative complications in the Clavien-Dindo [−0.59 (95% CI: −0.95 to −0.23), P=0.002] and the FABIB score [−0.65 (95% CI: −1.19 to −0.12), P=0.017]. An increase of the SMI did not result in less severe complications in the Clavien-Dindo [0.14 (95% CI: −0.27 to 0.55), P=0.503] or FABIB score [0.17 (95% CI: −0.42 to 0.76), P=0.572]. For patients classified as sarcopenic by the cut-off-based systems no relevant relation to postoperative complications was found. Overall survival was better for a higher MRA [hazard ratio (HR): 0.75 (95% CI: 0.58–0.97), P=0.029], as long-term survival was for a higher SMI [HR: 0.68 (95% CI: 0.47–0.96), P=0.031]. Only below van der Werf’s MRA cut-off the probability of overall and long-term survival was reduced [HR: 2.32 (95% CI: 1.18–4.54), P=0.015; 2.68 (95% CI: 1.25–5.74), P=0.011].ConclusionsThe MRA has a stronger influence on complications in the Clavien-Dindo classification and the liver-surgery specific FABIB score than the SMI. Continuous, non-categoric MRA and SMI values are superior to cut-off-based systems in predicting the outcome after major hepatic surgery.

Ep.Th.654Home Based Pre-Rehabilitation in Hepatic &amp; Pancreatic Oncological Surgery- A Way Forward for Improved Patient Outcome

Abstract Aims To ascertain the impact of ‘’Cost effective home-based pre-rehabilitation’’ on post-operative outcomes in patients undergoing major hepatic and pancreatic oncological surgery. Methods In this non-randomized comparative study (2019-2021), we included 36 patients having pancreatic or hepatic malignancy. In group I, patients were signed up for home-based pre-rehabilitation program and dietary modification. Group II; included patients who did not have rehabilitation. The two groups were compared for post-operative outcomes (post-operative complications, length of ITU and hospital stay) Results Mean age was 69.05±9.68 years in group I and 67.50±8.75 years in group II (p-value 0.61). Open approach was used in 02 (11.0%) patients in group I and in 09 (50%) patients in group II (p-value 0.01). More patients in group II needed admission in intensive care unit (ICU); 18 (100%) versus 11 (61.1%) in group II (p-value 0.0003). The group I had shorter length of hospital stay as compared to Group II (p-value 0.0001). There was no significant difference in post-operative complications between the groups. Conclusion Home based pre-rehabilitation, has shown beneficial outcomes in terms of less requirement for ITU admission post operatively, shorter length of hospital stay and cost effective method of pre rehabilitation.

The Protective Effect of Traditional Chinese Medicine on Liver Ischemia-Reperfusion Injury.

Liver ischemia-reperfusion (I/R) injury occurs during transplantation and major hepatic surgery, which may lead to postoperative liver dysfunction. More and more traditional Chinese medicines (TCMs) have been used to treat liver ischemia-reperfusion injury. The purpose of this review is to evaluate the different protective effects of TCMs in the treatment of liver ischemia-reperfusion injury and to summarize its possible mechanisms. The results indicate that TCMs attenuate liver I/R injury via multiple mechanisms, including antioxidation stress, anti-inflammatory response, antiapoptosis, and inhibiting endoplasmic reticulum stress. However, the in-depth mechanism of the protective effects of these traditional Chinese medicines still remains unknown.

Portal and hepatic vein embolization prior to major hepatectomy

To analyze safety and effectiveness of simultaneous portal and hepatic vein embolization (PHVE) or sequential hepatic vein embolization (HVE) compared to portal vein embolization (PVE) for future remnant liver (FRL) hypertrophy prior to major hepatic surgery. Patients undergoing PVE, PHVE or HVE at our tertiary care center between 2018 and 2020 were retrospectively included. FRLV, standardized FRLV (sFRLV) and sFRLV growth rate per day were assessed via volumetry, as well as laboratory parameters. 36 patients (f = 15, m = 21; median 64.5 y) were included, 16 patients received PHVE and 20 patients PVE, of which 4received sequential HVE. Significant increase of FRLV was achieved with both PVE and PHVE compared to baseline (p < 0.0001). sFRLV growth rate did not significantly differ following PHVE (2.2 ± 1.2 %/d) or PVE (2.2 ± 1.7 %/d, p = 0.94). Left portal vein thrombosis (LPVT) was observed after PHVE in 6 patients and in 1 patient after PVE. Sequential HVE showed a considerably high growth rate of 1.42 ± 0.45 %/d after PVE. PHVE effectively induces FRL hypertrophy but yields comparable sFRLV to PVE. Sequential HVE further induces hypertrophy after insufficient growth due to PVE. Considering a potentially higher rate of LPVT after PHVE, PVE might be preferred in patients with moderate baseline sFRLV, with optional sequential HVE in non-sufficient responders.

Variability of Standard Liver Volume by 2D Ultrasound: A Cross-sectional Study from Eastern India

Introduction: Liver volume estimation is an essential component prior to major hepatic surgery and liver transplantation. Liver volume is evaluated with different formulae, gold standard Computed Tomography (CT) volumetry and Magnetic Resonance Imaging (MRI). As per literature review, studies comparing ultrasonography with formula based liver volume estimation are very few. Ultrasonography is non-invasive in nature and inexpensive. It is gaining popularity among clinicians as it helps in rapid evaluation of liver volumes. Aim: To compare variability of liver volume using 2D ultrasound with a standard well-established method based on formula derived by Johnson et al. Materials and Methods: This was a cross-sectional study done between August-October 2020 and patients were selected by the physician from general Outpatient Department (OPD) pool and clinically screened for further biochemical studies. Participants aged 20-60 years with normal liver function test were recruited in the study. Images were taken on a Siemens Ultrasound System. Study variables included were liver volumes estimated by two methods, age, weight, height and Body Surface Area (BSA). F test was used to compare variability between liver volumes estimated by two different methods. Bivariate correlation between ultrasonography-based liver volume and different body indices was also tested. Results: Variability comparison using F test shows no significant difference (F=1.095, df1=149, df2=149, p=0.29). Liver volumes estimated by two methods showed good correlation with each other and is significant at the 0.01 level, r=0.574. The mean difference (125 cc) in volumes between two methods were statistically significant (t=10.92, degree of freedom=149, p&lt;0.001) and were not in agreement with each other. Body parameters were correlated with liver volume estimated by 2D ultrasound. Conclusion: Ultrasonography is a useful tool in estimating liver volume prior to major hepatic resection. Formula based calculation of Standard Liver Volume (SLV) does not agree with USG based volume and underestimates the mean liver volume obtained by USG method.

Perioperative changes in hemoglobin levels during major hepatopancreatic surgery in transfused and non-transfused patients.

Background:Several studies have shown that restrictive transfusion policies are safe. However, in clinical practice, transfusion policies seem to be inappropriate. In order to assist in decision-making concerning red blood cell transfusions, we determined perioperative hemoglobin (Hb) levels during major pancreatic and hepatic operations.Methods:Patients who underwent major pancreatic or hepatic resections between 2002 and 2011 were classified into the transfused (TF+) and non-transfused (TF) groups. The perioperative Hb values of these patients were evaluated at six points in time.Results:The study included 1596 patients, of which 785 underwent pancreatoduodenectomy, 79 total pancreatectomy, and 732 partial hepatectomy. Similar perioperative changes in Hb levels were seen in all patients regardless of whether they received a blood transfusion. In patients undergoing pancreatoduodenectomy and total pancreatectomy, the median of the lowest measured hemoglobin values was 89.2 g/L and in partial hepatectomy patients 92.6 g/L, and these were assumed to be the trigger points for red blood cell transfusion.Conclusions:Despite guidelines on blood transfusion thresholds, restrictive blood transfusion policies were not observed during our study period. After major pancreatic and hepatic surgery, Hb levels recovered without transfusions. This should encourage clinicians to obey the restrictive blood transfusion policies after major hepatopancreatic surgery.

Hepatectomy in Robotic Surgery

Scientists developed the robotic surgery system to offer a solution to the increased challenges of conventional laparoscopic surgery. Robotic surgery is a minimally invasive surgical procedure, but scientists have not yet validated it. Over recent years, the use of the laparoscopic technique for liver surgery has reduced like other abdominal techniques due to the limitations of laparoscopic instruments. Robotic procedures can help surgeons to overcome these challenges, particularly during complex operations. Researchers conducted a review of major hepatic surgery on PubMed using designated keywords. They analyzed 237 patients in 17 series and recorded outcomes, for example, length of hospital stays, estimated loss of blood, duration of operation, costs, conversation rate, and related difficulties. The study indicated wedge resection and segmentectomy which were mainly performed procedures. However, the predominance of significant hepatectomies through robotic surgery has high chances because of the superior activities obtained by the robotic system. The complication and conversation rates were 13.4% and 4.2%, respectively. Bile leaks and intracavitary fluid collections were the frequent occurring morbidities. The mean time for conducting the operation was 285 min, while the mean blood loss during the process was 50–280 ml. The mean post-operative duration the patient remained at the hospital was 7 days. The study did not record long-term and survival outcomes. A study conducted in Italy indicated that robotic liver surgery had gained increasing acceptance due to its significant advantage to both patients and operators. Operators have done over 100 robotic hepatic surgeries in Italy, where most robotic training facilities are active. Robotic surgery is safe and feasible in experienced hands. More research is necessary to evaluate the improvement in long-term oncological follow-up and outcomes.

Primary Tumor Location Is a Prognostic Factor for Intrahepatic Progression-Free Survival in Patients with Colorectal Liver Metastases Undergoing Portal Vein Embolization as Preparation for Major Hepatic Surgery.

The aim of this study was to identify prognostic factors affecting intrahepatic progression-free survival (ihPFS) and overall survival (OS) in patients with colorectal cancer liver metastases (CRCLM) undergoing portal vein embolization (PVE) and subsequent (extended) right hemihepatectomy. A total of 59 patients (mean age: 60.8 ± 9.3 years) with CRCLM who underwent PVE in preparation for right hemihepatectomy were included. IhPFS and OS after PVE were calculated using the Kaplan–Meier method. Cox regression analyses were conducted to investigate the association between the following factors and survival: patient age, laterality of the colorectal cancer (right- versus left-sided), tumor location (colon versus rectal cancer), time of occurrence of hepatic metastases (synchronous versus metachronous), baseline number and size of hepatic metastases, presence or absence of metastases in the future liver remnant (FLR) before PVE, preoperative carcinoembryogenic antigen (CEA) levels, time between PVE and surgery, history of neoadjuvant or adjuvant chemotherapy, and the presence or absence of extrahepatic disease before PVE. Median follow up was 18 months. The median ihPFS was 8.2 months (95% confidence interval: 6.2–10.2 months), and median OS was 34.1 months (95% confidence interval: 27.3–40.9 months). Laterality of the primary colorectal cancer was the only statistically significant predictor of ihPFS after PVE (hazard ratio (HR) = 2.242; 95% confidence interval: 1.125, 4.465; p = 0.022), with patients with right-sided colorectal cancer having significantly shorter median ihPFS than patients with left-sided cancer (4.0 ± 1.9 months versus 10.2 ± 1.5 months; log rank test: p = 0.018). Other factors, in particular also the presence or absence of additional metastases in the FLR, were not associated with intrahepatic progression-free survival. The presence of extrahepatic disease was associated with worse OS (HR = 3.050, 95% confidence interval: 1.247, 7.459; p = 0.015).

Salvage RFA in patients with intrahepatic recurrence after major hepatic surgery for colorectal cancer liver metastases: mid-term outcome.

To evaluate the mid-term outcome of salvage radiofrequency ablation (RFA) treatment in patients who exhibited intrahepatic recurrence after major hepatectomy for colorectal liver metastases (CRCLM). Observational study on 23 consecutive patients (mean age 59 ± 9years; 14/9 male/female) who, after a single (11/23) or multiple rounds (12/23) of major hepatic surgery, developed recurrent CRCLM in the liver remnant. Patients with a maximum of three metastases measuring up to 3cm, and without relevant extrahepatic disease, underwent CT-guided RFA. Using the Kaplan-Meier-method, median intrahepatic progression-free-survival (ihPFS) and overall survival (OS) times after salvage RFA were compared with the same patients' time between the respective last round of surgery and diagnosis of intrahepatic recurrence leading to RFA. Median follow-up was 26months (range 12-103months). Median ihPFS time after RFA was 8months (range 1-81months). Median ihPFS time after the respective last round of surgery and RFA in the same patients had been 5months (range 1-23months), thus yielding similar ihPFS times after surgery vs. after salvage RFA (p = 0.238; Mood's median test). After RFA, 15/23 (65%) of patients developed new hepatic metastases within the first year post-RFA. Median OS was 37months, with a 1-year OS rate of 100%, 3-year OS rate of 57%, and 5-year OS rate of 24%. No major complications were observed. Patients who exhibit intrahepatic recurrence of CRCLM after major hepatectomy will experience intrahepatic recurrence after salvage RFA as well, and after similar time intervals. However, long-term ihPFS may still be achieved in some patients. • Patients who exhibit intrahepatic recurrence of colorectal liver metastases after major hepatectomy will experience intrahepatic recurrence after salvage RFA as well, and after similar time intervals. • About two-thirds of all patients develop new metastases elsewhere in the liver within 1year after RFA. • However, long-term intrahepatic progression-free survival may still be achieved in some patients.

The Effect of 30-minute Ischemia on the Levels of IL6, TNFα, NO, Glutathione and Lactic Acid in the Hepatic Tissue of Rats with Hepatic Steatosis

Fatty liver disease (FLD) is becoming increasingly common. Ischemia-reperfusion injury (IRI) is the main pathogenic factor determining morbidity and mortality after major hepatic surgery. This experimental study investigated changes in the levels of interleukin 6 (IL6), tumor necrosis factor α (TNFα), nitric oxide (NO), glutathione (GSH) and lactic acid (LA) in hepatic tissue, in normal rats and rats with severe hepatic steatosis, after 30-minute hepatic ischemia and reperfusion. The aim was to evaluate the ability of the severely steatotic liver to sustain ischemia. The study was conducted on 96 male Wistar rats aged 12–14 weeks, in 48 of which severe hepatic steatosis was induced by administration of a choline-free diet for 12–14 weeks. The other 48 rats received standard laboratory diet for the same period. The effect of 30-minute hepatic ischemia and reperfusion was examined in 24 steatotic and 24 lean livers, which were subjected to hepatic ischemia-reperfusion injury. After 6 and 24 hours of reperfusion, the levels of IL6, TNFα, NO, LA and GSH in the liver tissue of all the rats were measured. The serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) were measured to determine the severity of hepatic injury, and the survival of the rats after surgery was assessed. Rats with steatotic livers subjected to 30-minute hepatic ischemia and reperfusion showed significantly higher liver values of TNFα and LA and significantly lower liver values of IL6, GSH and NO than lean rats. The serum levels of AST and ALT were higher in rats with severely steatotic livers than in those with lean livers, after 30-minute hepatic ischemia and reperfusion, and no rat with a steatotic liver survived surgery. Rats with steatotic livers undergoing 30-minute ischemia and reperfusion show significant elevation of TNFα and LA and reduction in IL6, GSH and NO in liver tissue, with poor survival after surgery, compared to non-steatotic rats. These findings suggest that steatotic livers are more susceptible to ischemia-reperfusion injury than lean livers.

Enterothorax After Hepatic Surgery: A Single‐Center Experience

Enterothorax (ET) is a rare complication after hepatic surgery. The literature in this field is limited and mainly based on case reports. The aim of this study was to review our department's experience. We retrospectively analyzed 602 patients who underwent hepatic resection between November 2008 and December 2016. Major hepatic surgery (n = 321) was defined as right or extended right hepatectomy (n = 227), left or extended left hepatectomy (n = 63), trisegmentectomy (n = 13), and living donor liver transplantation (n = 18). ET cases were identified by analyzing clinical courses and radiological imaging. ET was observed in five out of 602 patients (0.8%). All patients developed the complication after major hepatic surgery (five out of 321, 1.6%). ET exclusively occurred after right (n = 3) or extended right hepatectomy (n = 2). Median time to diagnosis was 22months. Radiological imaging showed herniation of small (n = 2), large bowel (n = 2), or omental fat (n = 1) with a median diaphragmatic defect of 3.9cm. Two patients presented with acute incarceration and underwent emergency surgery, one patient reported recurrent pain and underwent elective repair, and two patients refused surgery. Follow-up imaging in two operated patients showed no recurrence of ET after 36 and 8months. Patients after right hepatectomy have a substantial risk of ET. Acute right upper quadrant pain and/or dyspnea after hepatectomy should be investigated with adequate radiological imaging. Elective surgical repair of ET is recommended to avoid emergency surgery in case of incarceration.

Post-hepatectomy liver failure after major hepatic surgery: not only size matters

ObjectivesTo compare the value of functional future liver remnant (functFLR) to established clinical and imaging variables in prediction of post-hepatectomy liver failure (PHLF) after major liver resection.MethodsThis retrospective, cross-sectional study included 62 patients, who underwent gadoxetic acid enhanced MRI and MDCT within 10 weeks prior to resection of ≥ 4 liver segments. Future liver remnant (FLR) was measured in MDCT using semi-automatic software. Relative liver enhancement for each FLR segment was calculated as the ratio of signal intensity of parenchyma before and 20 min after i.v. administration of gadoxetic acid and given as mean (remnantRLE). Established variables included indocyanine green clearance, FLR, proportion of FLR, weight-adapted FLR and remnantRLE. functFLR was calculated as FLR multiplied by remnantRLE and divided by patient’s weight. The association of measured variables and PHLF was tested with univariate and multivariate logistic regression analysis and receiver operator characteristics (ROC) curves compared with the DeLong method.ResultsSixteen patients (25.8%) experienced PHLF. Univariate logistic regression identified FLR (p = 0.015), proportion of FLR (p = 0.004), weight-adapted FLR (p = 0.003), remnantRLE (p = 0.002) and functFLR (p = 0.002) to be significantly related to the probability of PHLF. In multivariate logistic regression analysis, a decreased functFLR was independently associated with the probability of PHLF (0.561; p = 0.002). Comparing ROC curves, functFLR showed a significantly higher area under the curve (0.904; p < 0.001) than established variables.ConclusionsfunctFLR seems to be superior to established variables in prediction of PHLF after major liver resection.Key Points• functFLR is a parameter combining volumetric and functional imaging information, derived from MDCT and gadoxetic acid enhanced MRI.• In comparison to other established methods, functFLR is superior in prediction of post-hepatectomy liver failure.• functFLR could help to improve patient selection prior major hepatic surgery.

Ischemia-Reperfusion Injury in Aged Livers-The Energy Metabolism, Inflammatory Response, and Autophagy.

Because of the lack of adequate organs, the number of patients with end-stage liver diseases, acute liver failure or hepatic malignancies waiting for liver transplantation is constantly increasing. Accepting aged liver grafts is one of the strategies expanding the donor pool to ease the discrepancy between the growing demand and the limited supply of donor organs. However, recipients of organs from old donors may show an increased posttransplantation morbidity and mortality due to enhanced ischemia-reperfusion injury. Energy metabolism, inflammatory response, and autophagy are 3 critical processes which are involved in the aging progress as well as in hepatic ischemia-reperfusion injury. Compared with young liver grafts, impairment of energy metabolism in aged liver grafts leads to lower adenosine triphosphate production and an enhanced generation of free radicals, both aggravating the inflammatory response. The aggravated inflammatory response determines the extent of hepatic ischemia-reperfusion injury and augments the liver damage. Autophagy protects cells by removal of damaged organelles, including dysfunctional mitochondria, a process impaired in aging and involved in ischemia-reperfusion-related apoptotic cell death. Furthermore, autophagic degradation of cellular compounds relieves intracellular adenosine triphosphate level for the energy depressed cells. Strategies targeting the mechanisms involved in energy metabolism, inflammatory response, and autophagy might be especially useful to prevent the increased risk for ischemia-reperfusion injury in aged livers after major hepatic surgery.

Perioperative outcome of elderly versus younger patients undergoing major hepatic or pancreatic surgery

ObjectiveThe aim of this study was to determine the safety of elderly cancer patients (≥70 years) undergoing hepatic resection (HR) or pancreaticoduodenectomy (PD) in comparison with younger adults (<70 years).MethodsA total of 1,012 consecutive patients undergoing HR or PD were included. The incidence and severity of morbidity were documented within 30 days postoperatively and compared between elderly and younger groups. Risk factors associated with postoperative morbidity were investigated by multivariate logistic regression analysis.ResultsElderly patients (n=111, 11.0%) had more comorbidities and worse preoperative general condition and liver function versus younger patients (n=901, 89.0%), and thus were more likely to develop infectious (eg, systemic sepsis and urinary tract infection, both p<0.01) and technical-associated complications (intraperitoneal bleeding and biliary/pancreatic fistula, p=0.029 and p=0.074, respectively). However, the incidence and severity of complications were comparable between elderly and younger patients in the whole cohort, and also in HR and PD surgery groups separately. Preoperative hemoglobin (odds ratio [OR] 1.4, p=0.007) and intraoperative blood transfusion (OR 1.9, p=0.002), rather than age, were independently associated with postoperative morbidity. Hepatitis (OR 2.9, p=0.001), preoperative hemoglobin (OR 1.6, p=0.036), and pancreatic versus hepatic surgery (OR 2.3, p=0.005) were independently associated with postoperative infectious. For elderly patients only, American Society of Anesthesiologists (ASA) score III (OR 2.1, p=0.033) and intraoperative blood transfusion (OR 3.2, p=0.030) were independently associated with postoperative morbidity.ConclusionHR and PD can be safely performed in selected elderly patients versus younger patients. Elderly patients with ASA score III or above should be cautiously selected for major surgeries.