Search Results (20)

Background: Interleukin-6 (IL-6) is used as a marker for infection and inflammation. After liver surgery, IL-6 is also crucial for hepatic regeneration. The value of IL-6 serum-levels to differentiate infection from imminent post-hepatectomy liver failure (PHLF) remains unclear. This review focuses on IL-6 and complications after liver resections, specifically PHLF and infections. Methods: A systematic review was performed in the PubMed, Embase, and Cochrane libraries from January 2000 to June 2025 according to PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). All English language human data publications were assessed. Results: Overall, 12 studies (n = 589 patients) evaluating perioperative serum IL-6 levels were included. Six publications reported PHLF rates, and two specifically addressed IL-6, PHLF, and infection. Several patient and surgical parameters influence IL-6 dynamics. Despite five randomized trials being published, the overall study quality was low, with a high risk of bias. In particular, IL-6 on the first postoperative day was associated with PHLF and infections, but multivariable analyses of confounding factors are lacking. A meta-analysis of studies with a specific cut-off calculation was precluded by heterogeneous cohorts and endpoints. Conclusions: IL-6 levels may have early diagnostic value regarding imminent infectious complications or PHLF early after liver resection, but the evidence is exploratory and limited by methodological weaknesses. At present, IL-6 as a single marker does not seem to show sufficient clinical discriminatory potential to differentiate between infection and impaired hepatic regeneration. Future studies should address confounding factors, ideal timepoints of assessment, different methods of serum IL-6 assays, specific cut-offs, and multi-marker combinations. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with liver metastases (CRLM) representing a common and often incurable manifestation. While surgical resection combined with chemotherapy remains the standard for resectable disease, a significant subset of patients presents with unresectable CRLM. Recent advances have positioned liver transplantation (LT) as a promising therapeutic option for select patients with unresectable CRLM. This review synthesizes current evidence from landmark studies—including the SECA and TRANSMET trials—and emerging data from North American cohorts, highlighting the evolution of patient selection criteria, prognostic indicators such as the Oslo score and metabolic tumor volume, and the role of living-donor and extended-criteria grafts. Outcomes from recent studies demonstrate that LT can achieve 5-year overall survival rates exceeding 70% in well-selected patients, rivaling those of traditional transplant indications. Ongoing trials such as SECA-III and SOULMATE aim to refine indications and address organ allocation challenges. Collectively, these findings suggest that LT can offer long-term survival benefits comparable to traditional transplant indications, marking a paradigm shift in the management of metastatic CRC. Full article

Background: Post-hepatectomy liver failure (PHLF) is the most worrisome complication after a major hepatectomy and is the leading cause of postoperative mortality. The most important predictor of PHLF is the future liver remnant (FLR), the volume of the liver that will remain after the hepatectomy, representing a major concern for hepatobiliary surgeons, radiologists, and patients. Therefore, an accurate preoperative assessment of the FLR and the prediction of PHLF are crucial to minimize risks and enhance patient outcomes. Recent radiomics and deep learning models show potential in predicting PHLF and the FLR by integrating imaging and clinical data. However, most studies lack external validation and methodological homogeneity and rely on small, single-center cohorts. This review outlines current CT-based approaches for surgical risk stratification and key limitations hindering clinical translation. Methods: A literature analysis was performed on the PubMed Dataset. We reviewed original articles using the subsequent keywords: [(Artificial intelligence OR radiomics OR machine learning OR deep learning OR neural network OR texture analysis) AND liver resection AND CT]. Results: Of 153 pertinent papers found, we underlined papers about the prediction of PHLF and about the FLR. Models were built according to machine learning (ML) and deep learning (DL) automatic algorithms. Conclusions: Radiomics models seem reliable and applicable to clinical practice in the preoperative prediction of PHLF and the FLR in patients undergoing major liver surgery. Further studies are required to achieve larger validation cohorts. Full article

Background: Post-hepatectomy liver failure (PHLF) is a serious complication following hepatic resection for Klatskin tumors, significantly affecting patient prognosis. Identifying reliable preoperative and early postoperative predictors of PHLF can help optimize patient outcomes and guide surgical planning. Method: We conducted a retrospective review of 34 patients who underwent hemi-hepatectomy for extrahepatic cholangiocarcinoma at Kosin University Gospel Hospital between April 2019 and April 2024, and at Chonnam National University Hwasun Hospital between September 2017 and April 2024. Demographics, laboratory data, and volumetric measurements including spleen volume, were analyzed to assess their roles in predicting PHLF. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the predictive value of these factors. Results: Elevated preoperative glucose levels and reduced future liver remnant to spleen ratio (FLR/SV) were significantly associated with an increased risk of PHLF. Additionally, elevated postoperative day 1 total bilirubin (POD 1 TB) was identified as a key postoperative predictor of PHLF. Multivariable analysis confirmed the significance of these factors, with FLR/SV, preoperative glucose, and POD 1 TB demonstrating good discriminative ability in ROC analysis, with AUC values of 0.779, 0.782, and 0.786 respectively. Conclusion: Preoperative glucose control, evaluation of FLR/SV, and early postoperative monitoring of TB are useful for improving outcomes in patients undergoing major hepatectomy for Klatskin tumors. Full article

Post-hepatectomy liver failure (PHLF) remains a significant risk for patients undergoing partial hepatectomy (PHx). Reliable prognostic markers and treatments to enhance liver regeneration are lacking. Plasma nanoparticles, including lipoproteins, exosomes, and extracellular vesicles (EVs), can reflect systemic and tissue-wide proteostasis and stress, potentially aiding liver regeneration. However, their role in PHLF is still unknown. Methods: Our study included nine patients with hepatocellular carcinoma (HCC) undergoing PHx: three patients with PHLF, three patients undergoing the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure, and three matched controls without complications after PHx. Patient plasma was collected before PHx as well as 1 and 5 days after. EVs were isolated by ultracentrifugation, and extracted proteins were subjected to quantitative mass spectrometry using a super-SILAC mix prepared from primary and cancer cell lines. Results: We identified 2625 and quantified 2570 proteins in the EVs of PHx patients. Among these, 53 proteins were significantly upregulated and 32 were downregulated in patients with PHLF compared to those without PHLF. Furthermore, 110 proteins were upregulated and 78 were downregulated in PHLF patients compared to those undergoing ALPPS. The EV proteomic signature in PHLF indicates significant disruptions in protein translation, proteostasis, and intracellular vesicle biogenesis, as well as alterations in proteins involved in extracellular matrix (ECM) remodelling and the metabolic and cell cycle pathways, already present before PHx. Conclusions: Longitudinal proteomic analysis of the EVs circulating in the plasma of human patients undergoing PHx uncovers proteomic signatures associated with PHLF, which reflect dying hepatocytes and endothelial cells and were already present before PHx. Full article

The incidence of colorectal cancer and colorectal liver metastases (CRLM) is increasing globally due to an interaction of environmental and genetic factors. A minority of patients with CRLM have surgically resectable disease, but for those who have resection as part of multimodal therapy for their disease, long-term survival has been shown. Precision surgery—the idea of careful patient selection and targeting of surgical intervention, such that treatments shown to be proven to benefit on a population level are the optimal treatment for each individual patient—is the new paradigm of care. Key to this is the understanding of tumour molecular biology and clinically relevant mutations, such as KRAS, BRAF, and microsatellite instability (MSI), which can predict poorer overall outcomes and a poorer response to systemic therapy. The emergence of immunotherapy and hepatic artery infusion (HAI) pumps show potential to convert previously unresectable disease to resectable disease, in addition to established systemic and locoregional therapies, but the surgeon must be wary of poor-quality livers and the spectre of post-hepatectomy liver failure (PHLF). Volume modulation, a cornerstone of hepatic surgery for a generation, has been given a shot in the arm with the advent of liver venous depletion (LVD) ensuring significantly more hypertrophy of the future liver remnant (FLR). The optimal timing of liver resection for those patients with synchronous disease is yet to be truly established, but evidence would suggest that those patients requiring complex colorectal surgery and major liver resection are best served with a staged approach. In the operating room, parenchyma-preserving minimally invasive surgery (MIS) can dramatically reduce the surgical insult to the patient and lead to better perioperative outcomes, with quicker return to function. Full article

Background: Previous studies have attempted to establish predictive models for post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) undergoing liver resection. However, a versatile and useful predictive model for PHLF remains to be developed. Therefore, we aimed to develop predictive models for PHLF based on type IV collagen 7s domain (7s collagen) in patients with HCC. Methods: We retrospectively collected data from 972 patients with HCC who had undergone initial curative liver resection between February 2000 and December 2020 at our hospital. Multivariate logistic regression analysis using a restricted cubic spline was performed to evaluate the effect of 7s collagen on the incidence of PHLF. A nomogram was developed based on 7s collagen. Results: PHLF grades B or C were identified in 104 patients (11%): 98 (10%) and 6 (1%) PHLF grades B and C, respectively. Multivariate logistic regression analysis revealed that the preoperative serum level of 7s collagen was significantly associated with a proportional increase in the risk of PHLF, which was confirmed in both laparoscopic and open liver resections. A nomogram was developed based on 7s collagen, with a concordance index of 0.768. The inclusion of 7s collagen values in the predictive model increased the predictive accuracy. Conclusion: The findings highlight the efficacy of the serum level of 7s collagen as a predictive factor for PHLF. Our novel nomogram using 7s collagen may be useful for predicting the risk of PHLF. Full article

Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies. Full article

Post-hepatectomy liver failure (PHLF) represents a major cause of morbidity and mortality after liver resection. The factors related to PHLF are represented not only by the volume and function of the future liver remnant but also by the severity of portal hypertension. The aim of this study was to assess whether the preservation of the round ligament (RL) may mitigate portal hypertension, thus decreasing the risk of PHLF and ascites in cirrhotic patients while undergoing minimally invasive liver surgery (MILS). All the cirrhotic patients who underwent MILS for HCC from 2016 to 2021 in two international tertiary referral centers were retrospectively analyzed, comparing cases with the RL preserved vs. those with the RL divided. Only patients with cirrhosis ≥ Child A6, portal hypertension, and ICG-R15 > 10% were included. Main postoperative outcomes were compared, and the risk factors for postoperative ascites (severe PHLF, grade B/C) were investigated through a logistic regression. After the application of the selection criteria, a total of 130 MILS patients were identified, with 86 patients with the RL preserved and 44 with the RL divided. The RL-preserved group showed lower incidences of severe PHLF (7.0% vs. 20.5%, p = 0.023) and ascites (5.8% vs. 18.2%, p = 0.026) in comparison with the RL-divided group. After uni/multivariate analysis, the risk factors related to postoperative ascites were RL division and platelets < 92 × 10³/µL, calculated with ROC analysis. The preservation of the round ligament during MILS may mitigate portal hypertension, preventing PHLF and ascites in cirrhotic patients with borderline liver function. Full article

(1) Background: Advancements in the field of liver surgery have led to a critical need for precise estimations of preoperative liver function to prevent post-hepatectomy liver failure (PHLF), a significant cause of morbidity and mortality. This study introduces a novel application of artificial intelligence (AI) in determining safe resection volumes according to a patient’s liver function in major hepatectomies. (2) Methods: We incorporated a deep learning approach, incorporating a unique liver-specific loss function, to analyze patient characteristics, laboratory data, and liver volumetry from computed tomography scans of 52 patients. Our approach was evaluated against existing machine and deep learning techniques. (3) Results: Our approach achieved 68.8% accuracy in predicting safe resection volumes, demonstrating superior performance over traditional models. Furthermore, it significantly reduced the mean absolute error in under-predicted volumes to 23.72, indicating a more precise estimation of safe resection limits. These findings highlight the potential of integrating AI into surgical planning for liver resections. (4) Conclusion: By providing more accurate predictions of safe resection volumes, our method aims to minimize the risk of PHLF, thereby improving clinical outcomes for patients undergoing hepatectomy. Full article

Triple combination conversion therapy, involving transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), has shown an encouraging objective response rate (ORR) and successful conversion surgery rate in initially unresectable hepatocellular carcinoma (HCC). However, the safety and long-term survival outcomes of subsequent liver resection after successful conversion still remain to be validated. From February 2019 to February 2023, 726 patients were enrolled in this retrospective study (75 patients received hepatectomy after conversion therapy [CLR group], and 651 patients underwent pure hepatectomy [LR group]). Propensity score matching (PSM) was used to balance the preoperative baseline characteristics. After PSM, 68 patients in the CLR group and 124 patients in the LR group were analyzed, and all the matching variables were well-balanced. Compared with the LR group, the CLR group experienced longer Pringle maneuver time, longer operation time, and longer hospital stays. In addition, the CLR group had significantly higher incidence rates of intra-abdominal bleeding, biliary leakage, post-hepatectomy liver failure (PHLF), and Clavien–Dindo grade IIIa complications than the LR group. There were no significant statistical differences in overall survival (OS) (hazard ratio [HR] 0.724; 95% confidence interval [CI] 0.356–1.474; p = 0.374) and recurrence-free survival (RFS) (HR 1.249; 95% CI 0.807–1.934; p = 0.374) between the two groups. Liver resection following triple combination conversion therapy in initially unresectable HCC may achieve favorable survival outcomes with manageable safety profiles; presenting as a promising treatment option for initially unresectable HCC. Full article

Objective: The aim of this study was to develop and validate an interpretable radiomics model based on two-dimensional shear wave elastography (2D-SWE) for symptomatic post-hepatectomy liver failure (PHLF) prediction in patients undergoing liver resection for hepatocellular carcinoma (HCC). Methods: A total of 345 consecutive patients were enrolled. A five-fold cross-validation was performed during training, and the models were evaluated in the independent test cohort. A multi-patch radiomics model was established based on the 2D-SWE images for predicting symptomatic PHLF. Clinical features were incorporated into the models to train the clinical–radiomics model. The radiomics model and the clinical–radiomics model were compared with the clinical model comprising clinical variables and other clinical predictive indices, including the model for end-stage liver disease (MELD) score and albumin–bilirubin (ALBI) score. Shapley Additive exPlanations (SHAP) was used for post hoc interpretability of the radiomics model. Results: The clinical–radiomics model achieved an AUC of 0.867 (95% CI 0.787–0.947) in the five-fold cross-validation, and this score was higher than that of the clinical model (AUC: 0.809; 95% CI: 0.715–0.902) and the radiomics model (AUC: 0.746; 95% CI: 0.681–0.811). The clinical–radiomics model showed an AUC of 0.822 in the test cohort, higher than that of the clinical model (AUC: 0.684, p = 0.007), radiomics model (AUC: 0.784, p = 0.415), MELD score (AUC: 0.529, p < 0.001), and ALBI score (AUC: 0.644, p = 0.016). The SHAP analysis showed that the first-order radiomics features, including first-order maximum 64 × 64, first-order 90th percentile 64 × 64, and first-order 10th percentile 32 × 32, were the most important features for PHLF prediction. Conclusion: An interpretable clinical–radiomics model based on 2D-SWE and clinical variables can help in predicting symptomatic PHLF in HCC. Full article

Background: Post-hepatectomy liver failure (PHLF) remains a complication with the potential risk of mortality for hepatocellular carcinoma (HCC) patients. The systemic inflammatory response (SIR) has been demonstrated to be associated with a bad prognosis of liver cirrhosis and tumors. This study aims to evaluate the incremental prognostic value of inflammatory markers in predicting PHLF in patients with HCC. Methods: Clinical characteristics and variables were retrospectively collected in 2824 patients diagnosed with HCC who underwent radical hepatectomy from the First Medical Center of the General Hospital of the People’s Liberation Army. A recently published prognostic model for PHLF was used as the reference model. The increase in AUC (ΔAUC), integrated discrimination improvement (IDI), and the continuous version of the net reclassification improvement (NRI) were applied for quantifying the incremental value of adding the inflammatory markers to the reference model. A p value < 0.05 was considered statistically significant. Results: The reference PHLF model showed acceptable prediction performance in the current cohort, with an AUC of 0.7492 (95%CI, 0.7191–0.7794). The calculated ΔAUC associated with procalcitonin (PCT) was the only one that was statistically significant (p < 0.05), with a value of 0.0044, and demonstrated the largest magnitude of the increase in AUC. The continuous NRI value associated with the systemic immune-inflammation index (SII) was 35.79%, second only to GPS (46.07%). However, the inflammatory markers of the new models with statistically significant IDI only included WBC count, lymphocyte count, and SII. IDI associated with SII, meanwhile, was the maximum (0.0076), which was consistent with the performance of using the ΔAUC (0.0044) to assess the incremental value of each inflammatory variable. Conclusions: Among a wide range of inflammatory markers, only PCT and SII have potential incremental prognostic value for predicting PHLF in patients with radical resectable HCC. Full article

Liver resection is the first curative option for most hepatic primary and secondary malignancies. However, post-hepatectomy liver failure (PHLF) still represents a non-negligible postoperative complication, embodying the most frequent cause of hepatic-related mortality. In the absence of a specific treatment, the most effective way to deal with PHLF is its prevention through a careful preoperative assessment of future liver remnant (FLR) volume and function. Apart from the clinical score and classical criteria to define the safe limit of resectability, new imaging modalities have shown their ability to assist surgeons in planning the best operative strategy with a precise estimation of the FLR amount. New technologies leading to liver and tumor 3D reconstruction may guide the surgeon along the best resection planes combining the least liver parenchymal sacrifice with oncological appropriateness. Integration with imaging modalities, such as hepatobiliary scintigraphy, capable of estimating total and regional liver function, may bring about a decrease in postoperative complications. Magnetic resonance imaging with hepatobiliary contrast seems to be predominant since it simultaneously integrates hepatic function and volume information along with a precise characterization of the target malignancy. Full article

Objective: To identify subgroups of patients with hepatocellular carcinoma (HCC) with different liver function reserves using an unsupervised machine-learning approach on the radiomics features from preoperative gadoxetic-acid-enhanced MRIs and to evaluate their association with the risk of post-hepatectomy liver failure (PHLF). Methods: Clinical data from 276 consecutive HCC patients who underwent liver resections between January 2017 and March 2019 were retrospectively collected. Radiomics features were extracted from the non-tumorous liver tissue at the gadoxetic-acid-enhanced hepatobiliary phase MRI. The reproducible and non-redundant features were selected for consensus clustering analysis to detect distinct subgroups. After that, clinical variables were compared between the identified subgroups to evaluate the clustering efficacy. The liver function reserve of the subgroups was compared and the correlations between the subgroups and PHLF, postoperative complications, and length of hospital stay were evaluated. Results: A total of 107 radiomics features were extracted and 37 were selected for unsupervised clustering analysis, which identified two distinct subgroups (138 patients in each subgroup). Compared with subgroup 1, subgroup 2 had significantly more patients with older age, albumin–bilirubin grades 2 and 3, a higher indocyanine green retention rate, and a lower indocyanine green plasma disappearance rate (all p < 0.05). Subgroup 2 was also associated with a higher risk of PHLF, postoperative complications, and longer hospital stays (>18 days) than that of subgroup 1, with an odds ratio of 2.83 (95% CI: 1.58–5.23), 2.41(95% CI: 1.15–5.35), and 2.14 (95% CI: 1.32–3.47), respectively. The odds ratio of our method was similar to the albumin–bilirubin grade for postoperative complications and length of hospital stay (2.41 vs. 2.29 and 2.14 vs. 2.16, respectively), but was inferior for PHLF (2.83 vs. 4.55). Conclusions: Based on the radiomics features of gadoxetic-acid-enhanced MRI, unsupervised clustering analysis identified two distinct subgroups with different liver function reserves and risks of PHLF in HCC patients. Future studies are required to validate our findings. Full article