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(1) Background: Patients with advanced chronic liver disease (ACLD) are living longer with more comorbidities because of improved medical and surgical management. However, patients with ACLD are at increased risk of perioperative morbidity and mortality; (2) Methods: We conducted a comprehensive review of the literature to support a narrative clinical guideline about the assessment of mortality risk and management of perioperative morbidity in patients with ACLD undergoing surgical procedures; (3) Results: Slight data exist to guide the perioperative management of patients with ACLD, and most recommendations are based on case series and expert opinion. The severity of liver dysfunction, portal hypertension, cardiopulmonary and renal comorbidities, and complexity of surgery and type (elective versus emergent) are predictors of perioperative morbidity and mortality. Expert multidisciplinary teams are necessary to evaluate and manage ACLD before, during, and after surgical procedures; (4) Conclusions: This clinical practice document updates the available data and recommendations to optimize the management of patients with advanced chronic liver disease who undergo surgical procedures.

Background New systemic chemotherapy agents have improved prognosis in patients with colorectal liver metastases (CLM), but some of them damage the liver parenchyma and ultimately increase postoperative morbidity and mortality after liver resection. The aims of our study were to determine the degree of hemodynamic and pathological liver injury in CLM patients receiving preoperative chemotherapy and to identify an association between these injuries and postoperative complications after liver resection. Methods This is a prospective descriptive study of patients with CLM receiving preoperative chemotherapy before curative liver resection from November 2013 to June 2014. All patients had preoperative elastography and hepatic hemodynamic evaluation. We analyzed clinical preoperative data and postoperative outcomes after grouping the patients by chemotherapy type, development of sinusoidal obstructive syndrome (SOS), and development of major complications. Results Eleven from the 20 patients included in the study received preoperative oxaliplatin-based chemotherapy (OBC). Nine patients had SOS at pathological analysis and five patients developed major complications. Patients receiving preoperative OBC had higher values of hepatic venous pressure gradient (HVPG) and developed more SOS and major complications. Patients developing SOS had higher values of HVPG and developed more major complications. Patients with major complications had higher values of HVPG, and patients with a HVPG of 5 mmHg or greater had more major complications than those under 5 mmHg (20 vs 80%, p  = 0.005). Conclusions OBC and SOS impair liver hemodynamics in CLM patients. An increase in major complications after liver resection in these patients develops at subclinical HVPG levels.

Few studies have assessed the clinical implications of the combination of different prognostic indicators for overall survival (OS) and disease-free survival (DFS) of resected hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic factors in HCC patients for OS and DFS outcomes and establish a nomogram-based prognostic model to predict the DFS of HCC. A multicenter, retrospective European study was conducted through the collection of data on 413 consecutive treated patients with a first diagnosis of HCC between January 2010 and December 2020. Univariate and multivariate Cox regression analyses were performed to identify all independent risk factors for OS and DFS outcomes. A nomogram prognostic staging model was subsequently established for DFS and its precision was verified internally by the concordance index (C-Index) and externally by calibration curves. For OS, multivariate Cox regression analysis indicated Child–Pugh B7 score (HR 4.29; 95% CI 1.74–10.55; p  = 0.002) as an independent prognostic factor, along with Barcelona Clinic Liver Cancer (BCLC) stage ≥ B (HR 1.95; 95% CI 1.07–3.54; p  = 0.029), microvascular invasion (MVI) (HR 2.54; 95% CI 1.38–4.67; p  = 0.003), R1/R2 resection margin (HR 1.57; 95% CI 0.85–2.90; p  = 0.015), and Clavien–Dindo Grade 3 or more (HR 2.73; 95% CI 1.44–5.18; p  = 0.002). For DFS, multivariate Cox regression analysis indicated BCLC stage ≥ B (HR 2.15; 95% CI 1.34–3.44; p  = 0.002) as an independent prognostic factor, along with multiple nodules (HR 2.04; 95% CI 1.25–3.32; p  = 0.004), MVI (HR 1.81; 95% CI 1.19–2.75; p  = 0.005), satellite nodules (HR 1.63; 95% CI 1.09–2.45; p  = 0.018), and R1/R2 resection margin (HR 3.39; 95% CI 2.19–5.25; < 0.001). The C-Index of the nomogram, tailored based on the previous significant factors, showed good accuracy (0.70). Internal and external calibration curves for the probability of DFS rate showed optimal consistency and fit well between the nomogram-based prediction and actual observations. MVI and R1/R2 resection margins should be considered as significant OS and DFS predictors, while satellite nodules should be included as a significant DFS predictor. The nomogram-based prognostic model for DFS provides a more effective prognosis assessment for resected HCC patients, allowing for individualized treatment plans.

Patients with advanced chronic liver disease (ACLD) or cirrhosis undergoing surgery have an increased risk of morbidity and mortality in contrast to the general population. This is a retrospective, observational study to evaluate the predictive capacity of surgical risk scores in European patients with ACLD. Cirrhosis was defined by the presence of thrombocytopenia with <150,000/uL and splenomegaly, and AST-to-Platelet Ratio Index >2, a nodular liver edge seen via ultrasound, transient elastography of >15 kPa, and/or signs of portal hypertension. We assessed variables related to 90-day mortality and the discrimination and calibration of current surgical scores (Child-Pugh, MELD-Na, MRS, NSQIP, and VOCAL-Penn). Only patients with ACLD and major surgeries included in VOCAL-Penn were considered (n = 512). The mortality rate at 90 days after surgery was 9.8%. Baseline disparities between the H. Mar and VOCAL-Penn cohorts were identified. Etiology, obesity, and platelet count were not associated with mortality. The VOCAL-Penn showed the best discrimination (C-statistic90D = 0.876) and overall predictive capacity (Brier90D = 0.054), but calibration was not excellent in our cohort. VOCAL-Penn was suboptimal in patients with diabetes (C-statistic30D = 0.770), without signs of portal hypertension (C-statistic30D = 0.555), or with abdominal wall (C-statistic30D = 0.608) or urgent (C-statistic180D = 0.692) surgeries. Our European cohort has shown a mortality rate after surgery similar to those described in American studies. However, some variables included in the VOCAL-Penn score were not associated with mortality, and VOCAL-Penn’s discriminative ability decreases in patients with diabetes, without signs of portal hypertension, and with abdominal wall or urgent surgeries. These results should be validated in larger multicenter and prospective studies.

Background: Liver function and the presence of portal hypertension, as well as the urgency and type of surgery, are prognostic factors in advanced chronic liver disease (ACLD) patients undergoing extrahepatic major surgeries. Emergent surgery in ACLD patients has 4–10 times higher mortality rates than elective surgery. However, perioperative management improvements have been made in recent years. Methods: This is a retrospective, observational, and unicentric study of 482 patients with ACLD who underwent major surgery from 2010 to 2019. We compared baseline characteristics and postoperative mortality according to the presence of ascites, the emergency, and the surgery period. Results: In total, 140 (29%) patients had ascites, and 191 (39.6%) underwent urgent surgeries. The 90-day mortality was 2.8-fold higher in patients with ascites [HR (95%CI) 2.8 (1.6–5.0); p = 0.001] and 3-fold higher in urgent surgeries [3.0 (1.6 − 5.5); p < 0.001)]. Urgent surgeries in patients with ascites revealed the highest mortality risk [6.3 (2.7–14.8); p < 0.001)], which persisted in current (2015–2019) surgeries [12.8 (2.9–56.5); p = 0.001)]. Portal hypertension was meaningful in patients undergoing abdominal surgery. Conclusions: ascites and emergent surgery increase the mortality risk of patients with ACLD despite the recent perioperative improvements.

To obtain proteomic profiles in patients with colorectal liver metastases (CRLM) and identify the relationship between profiles and the prognosis of CRLM patients. Prognosis prediction (favorable or unfavorable according to Fong's score) by a classification and regression tree algorithm of surface-enhanced laser desorption/ionization TOF-MS proteomic profiles from cryopreserved CRLM (patients) and normal liver tissue (controls). The protein peak 7371 showed the clearest differences between CRLM and control groups (94.1% sensitivity, 100% specificity, p < 0.001). The algorithm that best differentiated favorable and unfavorable groups combined 2970 and 2871 protein peaks (100% sensitivity, 90% specificity). Proteomic profiling in liver samples using classification and regression tree algorithms is a promising technique to differentiate healthy subjects from CRLM patients and to classify the severity of CRLM patients.

Background Neutrophil gelatinase-associated lipocalin (NGAL) expression is increased in epithelial cancer patients, but studies showing its relation to prognosis are scarce. We aimed to test the ability of preoperative serum NGAL levels (pNGAL) to predict recurrence in metastatic and nonmetastatic colorectal cancer (CRC) patients. Methods This retrospective study determined pNGAL levels in 60 healthy individuals, 47 patients with nonmetastatic CRC, and 70 patients with metastatic CRC undergoing curative neoplastic resection. Patients were divided into low- and high-pNGAL groups using a median series-based cutoff. Results The mean ± SD pNGAL in CRC patients (nonmetastatic and metastatic) was 102.3 ± 66.6 (median 91.4). Nonmetastatic CRC and metastatic CRC patients had higher pNGAL than healthy controls (88 ± 64 and 112 ± 67 vs. 0.6 ± 0.3, respectively, both p  < 0.0001). Nonmetastatic CRC patients with deeper tumor invasion and metastatic CRC patients with shorter disease-free interval after CRC resection had higher pNGAL. pNGAL levels correlated with neoplastic tissue volume. CRC patients with recurrence had higher pNGAL than those without recurrence (118 ± 64 vs. 88 ± 66, p  = 0.013), and high-pNGAL patients had a higher recurrence rate (59.3 vs. 36.2 %, p  = 0.016). Median pNGAL-based risk classification had a sensitivity of 62.5 % for predicting neoplastic progression in CRC patients and 74.3 % for predicting neoplastic progression during the first year after metastatic CRC resection. Conclusions pNGAL is higher in CRC patients than in the healthy population, which indicates a potential screening role. High-pNGAL levels are associated with higher neoplastic tissue volume, characteristics of neoplastic invasion, and recurrence, showing a prognostic utility mainly in metastatic CRC patients.

Background Few studies have studied the effects of graft quality on non-urgent liver retransplantation (ReLT) outcomes. We aimed to analyze graft characteristics and survival in non-urgent ReLT and the effect of using grafts with extended criteria on survival. Methods Eighty non-urgent ReLT were performed from June 1988 to June 2010. The whole series was divided by identical time periods to study time-related effects. We assessed graft quality with donor risk index (DRI) and Briceño scores and recipient status with the Model for End-stage Liver Diseases and Rosen scores. Low and high-risk grafts were defined by a DRI cutoff of 1.8. Results Graft survival was similar in both periods (1-, 5-, and 10-year graft survivals: 73.5, 46.9, and 40.8 versus 71, 47.7, and 47.7%, p  = 0.935) although donor quality was worse in the second period (DRI: 1.35 ± 0.32 vs. 1.66 ± 0.34, p  < 0.001). In the first period high-risk grafts did worse than low-risk grafts (5-year survival: 0 vs. 54.5%, p  = 0.002) while in the second period outcomes were similar (5-year survival: 48.6 vs. 56.7 %, p  = 0.660). Donor age was the only independent donor factor for graft survival, with lower survival when using grafts from donors over 60-years-old. Conclusions Graft quality in ReLT has worsened with time mainly because of older donors but nowadays the use of high-risk grafts in non-urgent ReLT is not associated with worse graft survival because of better perioperative management. Moreover of being selective on recipient conditions, care should be taken when using grafts from donors over 60-years-old for non-urgent ReLT.

In response to: S Sabour. Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases; rule of thumb.In response to: S Sabour. Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases; rule of thumb.

PurposeAlthough mortality and morbidity of severe acute calculous cholecystitis (ACC) are still a matter of concern, the impact of inadequate empirical antibiotic therapy has been poorly studied as a risk factor. The objective was to assess the impact of the adequacy of empirical antibiotic therapy on complication and mortality rates in ACC.MethodsThis observational retrospective cohort chart-based single-center study was conducted between 2012 and 2016. A total of 963 consecutive patients were included, and pure ACC was selected. General, clinical, postoperative, and microbiological variables were collected, and risk factors and consequences of inadequate treatment were analyzed.ResultsBile, blood, and/or exudate cultures were obtained in 76.3% of patients, more often in old, male, and severely ill patients (P < 0.001). Patients who were cultured had a higher overall rate of postoperative complications (47.4% vs. 29.7%; P < 0.001), as well as of severe complications (11.6% vs. 4.7%; P = 0.008). Patients with positive cultures had more overall complications (54.8% vs. 39.6%; P = 0.001), more severe complications (16.3% vs. 6.7%; P = 0.001), and higher mortality rates (6% vs. 1.9%; P = 0.012). Patients who received inadequate empirical antibiotic therapy had a fourfold higher mortality rate than those receiving adequate therapy (n = 283; 12.8% vs. 3.4%; P = 0.003). This association was especially marked in severe ACC TG–III patients (n = 132; 18.2 vs. 5.1%; P = 0.018) and remained a predictor of mortality in a binary logistic regression (OR 4.4; 95% CI 1.3–15.3).ConclusionPatients with positive cultures developed more complications and faced higher mortality. Adequate empirical antibiotic therapy appears to be of paramount importance in ACC, particularly in severely ill patients.