Prehabilitation programs in liver resection: a narrative review.

BACKGROUND AND OBJECTIVE: Liver resection (LR) is a commonly performed surgical procedure for the management of hepatocellular carcinoma and other liver conditions. Despite its benefits in providing patients a potential cure, it is also associated with significant postoperative complications and prolonged recovery periods. In recent years, pre-operative rehabilitation (prehabilitation) has emerged as an up-and-coming strategy to optimize patients' physical, psychological and functional status before LR, leading to improved surgical and patient postoperative outcomes. Hence, our review aims to explore and synthesize the existing literature on prehabilitation in LR to provide an overview of the current evidence to help guide physicians in managing their patients. METHODS: A comprehensive literature search was conducted in multiple electronic databases from inception to July 2023. The search strategy was tailored to capture studies investigating the role of prehabilitation in LR, and the factors that contribute to beneficial outcomes in the postoperative period. KEY CONTENT AND FINDINGS: Prehabilitation programs encompass a multifaceted approach to enhance surgical outcomes and patient well-being. This considers the specific needs of the varying patient populations, such as the elderly, or the cancer ridden. Improving physical fitness, nutritional supplementation and psychological support are the common tenets of prehabilitation. In physical prehabilitation, patients are engaged in intensive physical exercise often by means of a cycle ergometer. Addressing nutritional deficiencies through supplements and dietary interventions is also vital. Psychosocial assessments, advance care planning, music therapy, and progressive relaxation exercises are shown to enhance patient resilience and well-being. In addition, innovative approaches such as optimizing fluid balance, avoiding epidural analgesia, perioperative steroid administration, phosphate correction and branched-chain amino acid supplementation are being explored. CONCLUSIONS: Prehabilitation is important in optimizing patients before LR and is key in improving postoperative outcomes. Several prehabilitation strategies exist, but no formal consensus exists on patient selection and an ideal program.

Obesity and its influence on liver dysfunction, morbidity and mortality after liver resection.

Background: Obesity and associated steatosis is an increasing health problem worldwide. Its influence on post-hepatectomy liver failure (PHLF) and after liver resection (LR) is still unclear. Methods: Patients who underwent LR were investigated and divided into three groups [normal weight: body mass index (BMI) 18.5-24.9 kg/m2, overweight: BMI 25.0-29.9 kg/m2, obese: BMI ≥30 kg/m2] in this retrospective study. Primary aim of this study was to assess the influence of BMI and nonalcoholic steatohepatitis (NASH) on PHLF and morbidity. Results: Of 888 included patients, 361 (40.7%) had normal weight, 360 (40.5%) were overweight, 167 (18.8%) were obese. Median age was 62.5 years (IQR, 54-69 years). The primary indication for LR was colorectal liver metastases (CLM) (n=366, 41.2%). NASH was present in 58 (16.1%) of normal weight, 84 (23.3%) of overweight and 69 (41.3%) of obese patients (P<0.001). PHLF occurred in 16.3% in normal weight, 15.3% in overweight and 11.4% in obese patients (P=0.32). NASH was not associated with PHLF. There was no association between patients' weight and the occurrence of postoperative complications (P=0.45). At multivariable analysis, solely major LR [odds ratio (OR): 2.7, 95% confidence interval (CI): 1.83-4.04; P<0.001] remained a significant predictor for PHLF. Conclusions: Postoperative complications and PHLF are comparable in normal weight, overweight and obese patients and LRs using modern techniques can be safely performed in these patients.

Should more aggressive surgical resection be considered in the treatment for Bismuth types I and II hilar cholangiocarcinoma? A meta-analysis.

Evidence regarding the optical surgical extent for Bismuth type I/II HCCA is lacking. we aims to evaluate the optimal surgical methods for Bismuth type I/II HCCA. Studies comparing bile duct resection (BDR) and BDR combined with liver resection (BDR + LR) for all types of HCCA patients were searched for analyses, and 14 studies were finally included. The main outcomes were the R0 resection rate and overall survival (OS). For all types of HCCA patents, BDR + LR resulted with higher R0 resection rates when comparing with BDR only (RR = 0.70, 95%CI, 0.63-0.78), and patients with R0 resections had eight times longer median survival and more long-time survival outcomes (3 and 5 year OS) comparing to those with non-R0 resections. Bismuth I/II HCCA patients also showed longer median survival and 3-year OS after R0 resections (P = 0.04). Moreover, there was no significant difference in 3-year OS between BDR and BDR + LR (P = 0.89) and we additionally found BDR resulted in less mortality or morbidity rates. In Europe and US, they resulted the R0 resection rates could be comparable between BDR and BDR + LR (P = 0.18), and Bismuth type I HCCA accounted for 75.8%, while in Asia, BDR + LR still resulted with higher R0 resection rates (P < 0.0001) and the Bismuth type I HCCA accounted for only 40.3%. The surgical approaches may not directly impact patient prognosis, patients with R0 resections are usually associated with improved survival outcomes; for selected Bismuth type I/II HCCA, BDR may be an acceptable option with regard to lower morbidity and comparable R0 resection rate comparing with BDR + LR.

Prediction of outcomes by diffusion kurtosis imaging in patients with large (≥5 cm) hepatocellular carcinoma after liver resection: A retrospective study.

Purpose: To evaluate preoperative diffusion kurtosis imaging (DKI) in predicting the outcomes of large hepatocellular carcinoma (HCC) after liver resection (LR). Materials and methods: From January 2015 to December 2017, patients with a large (≥5cm) HCC who underwent preoperative DKI were retrospectively reviewed. The correlations of the mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) with microvascular invasion (MVI) or histological grade were analyzed. Cox regression analyses were performed to identify the predictors of recurrence-free survival (RFS) and overall survival (OS). A nomogram to predict RFS was established. P<0.05 was considered as statistically significant. Results: A total of 97 patients (59 males and 38 females, 56.0 ± 10.9 years) were included in this study. The MK, MD, and ADC values were correlated with MVI or histological grade (P<0.01). With a median follow-up time of 41.2 months (range 12-69 months), 67 patients (69.1%) experienced recurrence and 41 patients (42.3%) were still alive. The median RFS and OS periods after LR were 29 and 45 months, respectively. The 1-, 3-, and 5-year RFS and OS rates were 88.7%, 41.2%, and 21.7% and 99.0%, 68.3%, and 25.6%, respectively. MK (P<0.001), PVT (P<0.001), and ADC (P=0.033) were identified as independent predictor factors for RFS. A nomogram including the MK value for RFS showed the best performance, and the C-index was 0.895. Conclusion: The MK value obtained from DKI is a potential predictive factor for recurrence and poor survival, which could provide valuable information for guiding the efficacy of LR in patients with large HCC.

Liver resection versus liver transplantation for hepatocellular carcinoma within Milan criteria: a meta-analysis of 18,421 patients.

Background: Outcomes after liver resection (LR) and liver transplantation (LT) for hepatocellular carcinoma (HCC) are heterogenous and may vary by region, over time periods and disease burden. We aimed to compare overall survival (OS) and disease-free survival (DFS) between LT versus LR for HCC within the Milan criteria. Methods: Two authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan criteria. Meta-analyses and metaregression were conducted using random-effects models. Results: We screened 2,278 studies and included 35 studies with 18,421 patients. LR was associated with poorer OS [hazard ratio (HR) =1.44; 95% confidence interval (CI): 1.14-1.81; P<0.01] and DFS (HR =2.71; 95% CI: 2.23-3.28; P<0.01) compared to LT, with similar findings among intention-to-treat (ITT) studies. In uninodular disease, OS in LR was comparable to LT (P=0.13) but DFS remained poorer (HR =2.95; 95% CI: 2.30-3.79; P<0.01). By region, LR had poorer OS versus LT in North America and Europe (P≤0.01), but not Asia (P=0.25). LR had inferior survival versus LT in studies completed before 2010 (P=0.01), but not after 2010 (P=0.12). Cohorts that underwent enhanced surveillance had comparable OS after LT and LR (P=0.33), but cohorts undergoing usual surveillance had worse OS after LR (HR =1.95; 95% CI: 1.24-3.07; P<0.01). Conclusions: Mortality after LR for HCC is nearly 50% higher compared to LT. Survival between LR and LT were similar in uninodular disease. The risk of recurrence after LR is threefold that of LT.

Liver resection versus intensity-modulated radiation therapy for treatment of hepatocellular carcinoma with hepatic vein tumor thrombus: a propensity score matching analysis.

BACKGROUND: The presence of hepatic vein tumor thrombus (HVTT) is a major determinant of survival outcomes in hepatocellular carcinoma (HCC) patients. This study compared survival outcomes between liver resection (LR) and intensity-modulated radiation therapy (IMRT) in HCC patients with HVTT. METHODS: Data from patients who underwent LR or IMRT for HCC with HVTT at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. Their survival outcomes were compared before and after propensity score matching (PSM). RESULTS: Three hundred and seven HCC patients with HVTT who underwent either LR (n=140) or IMRT (n=167) were enrolled. PSM matched 82 pairs of patients. The overall survival (OS) and recurrence-free survival (RFS) rates were significantly higher for patients in the LR group than those in the IMRT group. On subgroup analysis, significantly better survival outcomes were obtained after LR than IMRT in patients with peripheral type of HVTT (pHVTT) and major type of HVTT (mHVTT). However, similar survival outcomes were obtained after LR and IMRT when the HVTT had developed into inferior vena cava tumor thrombus (IVCTT). CONCLUSIONS: LR resulted in significantly better survival outcomes in HCC patients with HVTT when compared to IMRT. Once the HVTT had developed IVCTT, LR and IMRT resulted in similarly bad survival outcomes.

Sequential Portal Vein Embolization and Percutaneous Radiofrequency Ablation for Future Liver Remnant Growth: A Minimally Invasive Alternative to ALPPS Stage-1 in Treatment of Hepatocellular Carcinoma.

Background: To evaluate the feasibility and efficacy of sequential portal vein embolization (PVE) and radiofrequency ablation (RFA) (PVE+RFA) as a minimally invasive variant for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) stage-1 in treatment of cirrhosis-related hepatocellular carcinoma (HCC). Methods: For HCC patients with insufficient FLR, right-sided PVE was first performed, followed by percutaneous RFA to the tumor as a means to trigger FLR growth. When the FLR reached a safe level (at least 40%) and the blood biochemistry tests were in good condition, the hepatectomy was performed. FLR dynamic changes and serum biochemical tests were evaluated. Postoperative complications, mortality, intraoperative data and long-term oncological outcome were also recorded. Results: Seven patients underwent PVE+RFA for FLR growth between March 2016 and December 2019. The median baseline of FLR was 353 ml (28%), which increased to 539 (44%) ml after 8 (7-18) days of this strategy (p < 0.05). The increase of FLR ranged from 40% to 140% (median 47%). Five patients completed hepatectomy. The median interval between PVE+RFA and hepatectomy was 19 (15-27) days. No major morbidity ≥ III of Clavien-Dindo classification or in-hospital mortality occurred. One patient who did not proceed to surgery died within 90 days after discharge. After a median follow-up of 18 (range 3-50) months, five patients were alive. Conclusion: Sequential PVE+RFA is a feasible and effective strategy for FLR growth prior to extended hepatectomy and may provide a minimally invasive alternative for ALPPS stage-1 for treatment of patients with cirrhosis-related HCC.

Liver transplantation: would it be the best and last chance of cure for hepatocellular carcinoma with major venous invasion?

BACKGROUND: Hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) signifies advanced disease, whether LT confers any survival superiority over resection remains uncertain. METHODS: A propensity score matched (PSM) analysis of liver transplantation (LT) and liver resection (LR) for HCC with PVTT was performed. RESULTS: A consecutive series of 88 patients who received either LT (10 DDLTs and 3 LDLTs) or LR (n=75) respectively were recruited. Before PSM, the LT group has a higher MELD score (17.3 vs. 7.8, P<0.001), lower serum AFP levels (96 vs. 2,164 ng/mL, P=0.017) and smaller tumour size (4 vs. 10 cm, P<0.001). The 5-year overall survival for LT and LR were 55.4% and 15.9% respectively (P=0.007). After matching for serum AFP levels and tumour size, 1-, 3- and 5-year overall survival for LT were 81 ng/mL, 3.9 cm, 80%, 70% and 70% and the corresponding rates for LR were 1,417 ng/mL, 5.3 cm, 51.8%, 19,6% and 9.8% (P value =0.12, 0.27 and 0.009 respectively). CONCLUSIONS: LT is associated with significantly better oncological outcomes in HCC patients with PVTT involving the lobar or segmental level. A modest expansion of selection criteria to include small HCC with segmental PVTT should be considered.

Treatment strategy for hepatocellular carcinoma in China: radiofrequency ablation versus liver resection.

Hepatocellular carcinoma is the most common malignancy in liver, is also a global problem and is the fourth most commonly diagnosed cancers among men and the fourth leading causes of cancer death among both men and women in China. Liver resection or hepatic resection and radiofrequency ablation is widely accepted as a first-line surgical approach for hepatocellular carcinoma in China. However, the indications of radiofrequency ablation or hepatic resection are different and not unified in China. In this article, we review the current status of hepatic resection and radiofrequency ablation therapies in hepatocellular carcinoma management in China.

Liver resection for hepatocellular carcinoma in patients with portal hypertension: the role of laparoscopy.

Liver resection (LR) for hepatocellular carcinoma (HCC) in patients with chronic liver disease (CLD) is a major issue since patients are at risk of serious intraoperative and postoperative complications. The current EASL/AASLD guidelines recommend LR only in case of patients with stage A HCC with well-preserved liver function and consider the presence of portal hypertension (PHT) as a contraindication to surgery. Nevertheless, the literature on this topic is conflicting. Recently several studies reported that favorable outcomes can be achieved with a careful patients' selection in high volume centers. Laparoscopic LR, when performed by well-trained surgeons and with appropriate indications, proved to be a valid option for the surgical treatment of HCC on cirrhosis offering similar oncologic outcomes but a reduction in surgical related morbidities. Laparoscopic LR thanks to a reduction in the incidence of post-operative liver failure and ascites development in comparison to standard open LR could, in selected cases challenge alternative treatments in the treatment of HCC patients with preserved liver function and clinical signs of mild PHT.