Abstract
Background
Elderly patients with hepatocellular carcinoma (HCC) are particularly vulnerable to postoperative complications after liver resection. Evidence on enhanced recovery after surgery (ERAS) specifically in elderly individuals undergoing laparoscopic hepatectomy for HCC remains limited.
Methods
We retrospectively analyzed elderly patients (70–85 years) with pathologically confirmed HCC who underwent elective laparoscopic hepatectomy at a single tertiary center between June 2018 and June 2024. Patients managed with a standardized ERAS pathway were compared with those receiving conventional perioperative care. Propensity score matching (1:1) was performed based on demographic characteristics, comorbidities, liver function, and surgical factors. The primary endpoint was postoperative length of stay (LOS). Secondary endpoints included time to gastrointestinal recovery, postoperative pain scores, complications (Clavien–Dindo classification), rates of pleural effusion, 30-day readmission, and total hospitalization costs.
Results
After matching, baseline characteristics were well balanced between the ERAS and conventional care groups. Compared with conventional care, the ERAS group achieved earlier gastrointestinal recovery (shorter time to first flatus and liquid diet) and shorter urinary catheterization. Median postoperative LOS was significantly reduced, and total hospitalization costs were lower in the ERAS group. ERAS patients reported lower pain scores on postoperative days 1 and 3 and experienced fewer overall and pulmonary complications, particularly pleural effusion, without an increase in life-threatening (Clavien–Dindo grade IV–V) complications or 30-day readmissions.
Conclusions
In carefully selected elderly patients undergoing laparoscopic hepatectomy for HCC, implementation of an ERAS protocol appears safe and feasible, and is associated with accelerated recovery, fewer complications, and reduced healthcare costs compared with conventional perioperative care. Prospective multicenter studies are warranted to confirm these findings and to further define the role of ERAS in more vulnerable elderly subgroups.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12893-026-03855-7.
Keywords: Hepatocellular carcinoma, Enhanced recovery after surgery, Laparoscopic hepatectomy, Elderly, Postoperative outcomes
Introduction
Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and the third leading cause of cancer-related mortality [1, 2]. In recent years, increasing life expectancy and population aging have contributed to a rising incidence of HCC among elderly individuals in many countries [3, 4]. Surgical resection remains the standard curative treatment for early-stage HCC. With the advancement and widespread adoption of laparoscopic techniques, laparoscopic liver resection has emerged as a safe and effective option for carefully selected elderly patients [5, 6]. Nevertheless, elderly patients present unique perioperative challenges, including reduced physiological reserve, multiple comorbidities, and heightened vulnerability to postoperative complications [7–10].
Enhanced Recovery After Surgery (ERAS) is a multidisciplinary, evidence-based perioperative care pathway designed to attenuate surgical stress, accelerate postoperative recovery, and improve clinical outcomes. ERAS protocols require close collaboration among surgeons, anesthesiologists, nurses, nutritionists, pharmacists, physical therapists, respiratory therapists, and family caregivers [11, 12]. Over the past two decades, extensive research has shown that ERAS can reduce postoperative pain, shorten postoperative length of stay (LOS), and decrease complication rates across multiple surgical specialties, including colorectal, urological, orthopedic, vascular, and hepatic surgery [13–19].
Although ERAS guidelines for liver surgery have been increasingly refined and validated in general hepatectomy populations and patients undergoing hepatectomy for colorectal liver metastases [20–24], their applicability to patients with HCC, particularly elderly patients, remains uncertain. Patients with HCC often have chronic liver disease, cirrhosis, portal hypertension, thrombocytopenia, hypoalbuminemia, and impaired hepatic reserve, which may increase liver-specific postoperative risks and modify recovery after hepatectomy [25–27]. However, few studies have specifically evaluated ERAS in elderly patients undergoing laparoscopic liver resection for HCC. To address this gap, the present study evaluated the clinical efficacy and safety of an ERAS protocol in this specific population.
Materials and methods
Patients
This retrospective study analyzed elderly patients with HCC who underwent laparoscopic liver resection at Ningbo No. 2 Hospital between January 2018 and December 2024. The inclusion criteria were as follows: (1) age between 70 and 85 years; (2) histologically confirmed HCC after resection; (3) preoperative liver function classified as Child–Pugh class A or B; and (4) isolated laparoscopic hepatectomy without concomitant major procedures (e.g., bile duct resection or reconstruction). The exclusion criteria were: (1) conversion to open surgery for any reason; (2) concomitant major organ resection; (3) planned postoperative intensive care unit (ICU) admission based on preoperative assessment and anticipated need for intensive postoperative monitoring; and (4) incomplete clinical data for the main outcome assessment. Patients initially managed under the ERAS pathway but with incomplete adherence to individual ERAS components were not excluded solely for this reason and were included in the intention-to-treat sensitivity analysis.
Patients aged 70–85 years were included because, at our institution, patients older than 85 years are generally not considered routine candidates for hepatic tumor resection and are more commonly managed with non-surgical or less invasive treatments after multidisciplinary evaluation.
A total of 179 patients meeting the eligibility criteria were included. The ERAS protocol was officially implemented at our institution in January 2021. According to the perioperative care pathway received, 94 patients were included in the ERAS group and 85 patients were included in the conventional care group. All procedures were performed by senior hepatobiliary surgeons with extensive experience in laparoscopic liver resection.
The study protocol was approved by the Ethics Committee of Ningbo No. 2 Hospital. Written informed consent for participation in the ERAS program and for the use of clinical data in research was obtained from all patients.
Sample size calculation
The primary outcome of this study was postoperative LOS. Therefore, the sample size calculation was based on the expected difference in postoperative LOS between the ERAS and conventional care groups. Previous studies [22, 28] on ERAS in liver surgery reported a reduction in postoperative LOS of approximately 3–5 days. Because the standard deviation of LOS was not consistently reported in these studies and LOS was commonly presented as median with interquartile range, the standard deviation was approximated from the interquartile range using the formula SD ≈ IQR/1.35 where applicable.
To avoid overestimating the treatment effect, we performed a sensitivity sample size estimation using assumed standard deviations of 2, 3, 4, and 5 days. With a two-sided type I error rate of 0.05, a statistical power of 80% (β = 0.20), and a 1:1 allocation ratio, the most conservative scenario, assuming a 3-day difference in postoperative LOS and an SD of 5 days, required 45 patients per group. After allowing for approximately 10% potential exclusions or unmatched cases after propensity score matching, at least 50 patients per group were required. The final matched cohort included 65 patients per group, which met this requirement.
Perioperative management
Patients in the conventional care group received standard perioperative management, which included routine preoperative education and fasting instructions. Oral intake of food or fluids was prohibited after 8:00 PM on the evening before surgery. No bowel preparation was performed in either group before surgery.
Patients in the ERAS group were instructed to consume 400 mL of carbohydrate-rich solution orally 2 h before surgery. Both surgeons and nursing staff provided comprehensive preoperative counseling covering surgical objectives, procedural principles, potential risks, postoperative self-care, and recovery expectations. Nutritional status was evaluated using the Nutritional Risk Screening 2002 (NRS-2002) tool, and individualized nutritional support was implemented when indicated. Patients with chronic respiratory conditions or a history of prolonged smoking received tailored preoperative respiratory interventions.
Intraoperative care and anesthesia
In both groups, prophylactic antibiotics were administered, and tracheal intubation under general anesthesia was performed. A urinary catheter was inserted after induction, and intermittent pneumatic compression devices were applied for venous thromboembolism prevention. Intraoperative cell salvage was not routinely used as part of the standard perioperative pathway in either group. When considered necessary, it was applied selectively according to the joint judgment of the anesthesiologist and operating surgeon, mainly in patients with anticipated or actual major intraoperative blood loss.
In the ERAS group, additional measures included local infiltration of 0.25% bupivacaine at the incision site for intraoperative analgesia, and maintenance of normothermia using combined upper- and lower-body warming devices. These measures were not used in the conventional care group. In contrast, the conventional care group routinely received nasogastric tube placement prior to anesthesia induction, whereas nasogastric tube placement was omitted in the ERAS group unless clinically indicated.
Postoperative
Dietary progression
Postoperative oral intake was not mandatory at fixed time points in either group and was adjusted according to each patient’s clinical condition, gastrointestinal recovery, tolerance of oral intake, presence of nausea or vomiting, and the assessment of the surgical and nursing teams. In the ERAS group, dietary advancement was accelerated compared with conventional care. Patients were encouraged to chew gum immediately after surgery to stimulate gastrointestinal motility and were actively encouraged to resume oral intake earlier when clinically appropriate, usually beginning with a liquid diet approximately 12 h postoperatively and advancing to a semi-liquid diet approximately 24 h postoperatively as tolerated. In the conventional care group, dietary advancement followed routine clinical practice and was generally more conservative, with a liquid diet usually considered approximately 24 h after surgery and further advancement guided by bowel function recovery, oral intake tolerance, and clinical judgment.
Early mobilization
For patients in the ERAS group, limb movement exercises in bed were initiated immediately upon recovery from anesthesia. Ambulation aimed at preventing lower-limb deep vein thrombosis began on postoperative day (POD) 1. In the conventional care group, limb exercises in bed were introduced only on POD 1, without immediate early mobilization.
Pain management
Both groups received postoperative analgesia via intravenous patient-controlled analgesia (PCA) pumps. In the ERAS group, flurbiprofen axetil 50 mg was administered intravenously every 12 h, complemented by oral tramadol 50–100 mg twice daily. Pain intensity was assessed every 6 h, with adjustment of analgesic regimens based on pain scores; opioid use was intentionally avoided whenever possible. In the conventional care group, pain scores were evaluated every 12 h, and flurbiprofen axetil 50 mg intravenously or tramadol 50 mg intramuscularly was administered on demand. Opioids were permitted if clinically indicated.
Prevention of postoperative nausea and vomiting (PONV)
A multimodal antiemetic strategy was implemented in the ERAS group, whereas the conventional care group received antiemetic medication only when symptoms occurred. The detailed protocol for multimodal PONV prevention used in our institution is illustrated in Supplementary Fig. 1. Table 1 provides a detailed list of these criteria.
Table 1.
Perioperative management in the ERAS and conventional care groups
| ERAS group | Conventional care group |
|---|---|
| Before surgery | |
| Preoperative ERAS education (including surgical objectives, procedural principles, surgical risks, postoperative self-care, and other relevant components) | Routine health education on standard care |
| No bowel preparation | No bowel preparation |
| Normal oral nutrition until midnight | Normal oral nutrition until eight o’clock at night |
| Balloon-blowing exercise, 15 min per session, 7 times daily | No |
| Nutritional status was assessed and optimized based on the NRS-2002 scoring system | Conventional nutritional support |
| Day of surgery | |
| Carbohydrate drinks up to 2 h before surgery | No |
| Combined tracheal intubation and general anesthesia | Combined tracheal intubation and general anesthesia |
| Local anesthesia (0.25% Bupivacaine) | No local anesthesia |
| No nasogastric tube | Routine nasogastric tube drainage |
| Upper and lower body air-warming device | No |
| Routine patient-controlled analgesia pump | Routine patient-controlled analgesia pump |
| Days after surgery | |
| Pain | |
| Flurbiprofen axetil 50 mg iv q12h × 48 h and 50–100 mg Tramadol twice a day by oral. Pain scores q6h, adjust analgesia PRN. | PRN analgesia: flurbiprofen axetil 50 mg iv or tramadol 50 mg im. Pain scores q12h. |
| Diet | |
| Gum chewing stimulates salivation and gastrointestinal motility | No |
| PONV-multimodal approach | Antiemetics PRN for nausea |
| Start liquids 12 h postop | Start liquids 24 h postop |
| Start semiliquid diet 24 h postop | Start semiliquid diet after first flatus |
| Activity | |
| Post-awakening limb mobilization and repositioning to prevent DVT。 | Bed rest |
| On POD1, assist patient with 30-30-30 mobilization protocol (supine→sit→stand)。 | Guide patient through bed exercises on POD1 |
| Other | |
| Prevent pulmonary complications with sequential ‘inhale-clap-cough’ secretion clearance technique, guided bedside by nursing team | Routine back percussion for secretion clearance |
| Remove urinary catheter on POD1 | remove urinary catheter on POD2 |
ERAS Enhanced Recovery After Surgery, PONV postoperative nausea and vomiting, DVT deep venous thrombosis, POD postoperative day, PRN pro re nata
Discharge criteria
Patients were eligible for discharge when all of the following criteria were met: (1) Independent performance of basic activities of daily living. (2) Normothermia. (3) Stable vital signs and organ function. (4) Adequate pain control with oral analgesics. (5) Ability to tolerate normal oral diet. (6) Absence of clinical or laboratory signs of infection. (7) All above criteria met and patient’s willingness to be discharged.
Statistical analysis
Statistical analyses were performed using IBM SPSS Statistics version 23.0 and R version 4.3.1. Sample size was estimated using PASS 15 software. Continuous variables were presented as mean ± standard deviation or median with interquartile range, as appropriate, and categorical variables as frequencies and percentages. Between-group comparisons were performed using Student’s t test or the Mann–Whitney U test for continuous variables and the chi-square test or Fisher’s exact test for categorical variables, as appropriate. A two-sided P value < 0.05 was considered statistically significant.
Propensity score matching (PSM) was used to balance baseline characteristics between the ERAS and conventional care groups. Propensity scores were estimated using a multivariable logistic regression model including sex, age, diabetes, hypertension, history of cardiac disease, history of renal disease, body mass index (BMI), hepatitis B surface antigen status, Child–Pugh classification, alpha-fetoprotein level, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum albumin (ALB), total bilirubin, Eastern Cooperative Oncology Group (ECOG) performance status, presence of cirrhosis, American Society of Anesthesiologists (ASA) classification, and extent of surgery. Patients were matched at a 1:1 ratio using nearest-neighbor matching without replacement, with a caliper width of 0.2 of the standard deviation of the logit of the propensity score. Covariate balance was assessed using standardized mean differences, with an absolute value < 0.1 indicating adequate balance.
An intention-to-treat sensitivity analysis was performed. Patients initially managed under the ERAS pathway were retained in the ERAS group regardless of subsequent incomplete adherence to individual ERAS components. Seven patients with incomplete ERAS adherence were re-included, and PSM was re-performed using the same covariates and matching method as in the primary analysis.
To account for temporal variation in hospitalization costs, total hospitalization costs were standardized to 2024 Chinese yuan (CNY) using the annual consumer price index (CPI). Adjusted costs were calculated as original cost × 2024 CPI index / CPI index in the year of surgery.
An exploratory subgroup analysis was performed according to the extent of hepatectomy. Minor hepatectomy was defined as local tumor enucleation or resection of two or fewer liver segments, whereas major hepatectomy was defined as resection of three or more liver segments. Within each subgroup, perioperative and postoperative outcomes were compared between the ERAS and conventional care groups.
Follow-up
Patients in both groups were followed for 30 days after discharge. Outcomes recorded included postoperative mortality, morbidity, and readmission rates within the follow-up period.
Outcome measures
The primary outcome measure of the study was LOS, defined as the number of days from surgery to discharge. Secondary endpoints included: (1) Postoperative complications, classified according to the Clavien–Dindo grading system. (2) Total hospitalization costs. (3) Postoperative pain levels, evaluated using the Visual Analog Scale (VAS), ranging from 0 (no pain) to 10 (worst imaginable pain). (4) Readmission rate within 30 days post-discharge.
Outcome
Figure 1 illustrates the patient enrollment process. Between January 2018 and December 2024, a total of 179 eligible patients were recruited, including 94 in the ERAS group and 85 in the conventional care group. After PSM, 65 patients remained in each group. Baseline characteristics before and after PSM are summarized in Table 2. No significant differences were detected, indicating adequate comparability between groups.
Fig. 1.
Diagram of patient screening
HCC, hepatocellular carcinoma; PSM, propensity score matching
Table 2.
Baseline characteristics of patients before and after PSM
| Characteristics | Before PSM | After PSM | ||||||
|---|---|---|---|---|---|---|---|---|
| ERAS (n = 94) |
Conventional care (n = 85) |
p value | SMD | ERAS (n = 65) |
Conventional care (n = 65) |
p value | SMD | |
| Sex | 0.901 | 0.019 | 0.100 | 0.000 | ||||
| Male | 50 (53.2) | 46 (54.1) | 39 (60.0) | 39 (60.0) | ||||
| Female | 44 (46.8) | 39 (45.9) | 26 (40.0) | 26 (40.0) | ||||
| Age (years) | 73.0 (71.0,75.8) |
74.0 (72.0,78.0) |
0.198 | 0.146 |
74.0 (72.0, 77.0) |
74.0 (72.0, 78.0) |
0.781 | 0.040 |
| Diabetes, (n%) | 37 (39.4) | 38 (44.7) | 0.469 | 0.109 | 24 (36.9) | 27 (41.5) | 0.590 | 0.096 |
| Hypertension, (n%) | 47 (50.0) | 39 (46.0) | 0.582 | 0.082 | 30 (46.2) | 30 (46.2) | 0.100 | 0.000 |
| Cardiac history, (n%) | 16 (17.0) | 11 (12.9) | 0.446 | 0.109 | 10 (15.4) | 10 (15.4) | 0.100 | 0.000 |
| Kidney disease history, (n%) | 6 (6.4) | 3 (3.5) | 0.596 | 0.117 | 2 (3.1) | 2 (3.1) | 1.000 | 0.000 |
| BMI, (n%) | 0.043 | 0.858 | ||||||
| < 18.5 (kg/m2) | 17 (18.1) | 5 (5.9) | 0.317 | 6 (9.2) | 5 (7.7) | 0.053 | ||
| 18.5–24 (kg/m2) | 52 (55.3) | 56 (65.9) | 0.212 | 39 (60.0) | 42 (64.6) | 0.094 | ||
| > 24 (kg/m2) | 25 (26.6) | 24 (28.2) | 0.037 | 20 (30.8) | 18 (27.7) | 0.067 | ||
| Child-Pugh, (n%) | 0.886 | 0.022 | 0.818 | 0.041 | ||||
| A | 76 (80.9) | 68 (80.0) | 54 (83.1) | 53 (81.5) | ||||
| B | 18 (19.2) | 17 (20.0) | 11 (16.9) | 12 (18.5) | ||||
| ECOG-PS score, (n%) | 0.081 | 0.278 | 0.846 | 0.034 | ||||
| 0 | 70 (74.5) | 53 (62.4) | 46 (70.8) | 47 (72.3) | ||||
| 1–2 | 24 (25.5) | 32 (37.6) | 19 (29.2) | 18 (27.7) | ||||
| ASA grade, (n%) | 0.240 | 0.633 | ||||||
| I | 11 (11.7) | 4 (4.7) | 0.218 | 7 (10.8) | 4 (6.2) | 0.149 | ||
| II | 66 (70.2) | 64 (75.3) | 0.111 | 45 (69.2) | 48 (73.8) | 0.100 | ||
| Ⅲ | 17 (18.1) | 17 (20.0) | 0.050 | 13 (20.0) | 13 (20.0) | 0.000 | ||
| Alanine aminotransferase, (n%) | 0.901 | 0.019 | 0.592 | 0.095 | ||||
| < 40 U/L | 50 (53.2) | 46 (54.1) | 40 (61.5) | 37 (56.9) | ||||
| ≥ 40 U/L | 44 (46.8) | 39 (45.9) | 25 (38.5) | 28 (43.1) | ||||
| Aspartate aminotransferase, (n%) | 0.554 | 0.089 | 0.860 | 0.031 | ||||
| < 40 U/L | 39 (41.5) | 39 (45.9) | 30 (46.2) | 31 (47.7) | ||||
| ≥ 40 U/L | 55 (58.5) | 46 (54.1) | 35 (53.8) | 34 (52.3) | ||||
| Total bilirubin, (n%) | 0.589 | 0.082 | 0.855 | 0.032 | ||||
| < 17.1 µmol/L | 59 (62.8) | 50 (58.8) | 41 (63.1) | 42 (64.6) | ||||
| ≥ 17.1 µmol/L | 35 (37.2) | 35 (41.2) | 24 (36.9) | 23 (35.4) | ||||
| Baseline AFP, (n%) | 0.072 | 0.276 | ||||||
| < 400 ng/mL | 35 (37.2) | 43 (50.6) | 27 (41.5) | 27 (41.5) | 1.000 | 0.000 | ||
| ≥ 400 ng/mL | 59 (62.8) | 42 (49.4) | 38 (58.5) | 38 (58.5) | ||||
| HBsAg, (n%) | 0.622 | 0.076 | 1.000 | 0.000 | ||||
| Seropositive | 81 (86.2) | 71 (83.5) | 55 (84.6) | 55 (84.6) | ||||
| Seronegative | 13 (13.8) | 14 (16.5) | 10 (15.4) | 10 (15.4) | ||||
| Liver cirrhosis, (n%) | 0.937 | 0.012 | 1.000 | 0.000 | ||||
| With | 47 (50.0) | 42 (49.4) | 33 (50.8) | 33 (50.8) | ||||
| Without | 47 (50.0) | 43 (50.6) | 32 (49.2) | 32 (49.2) | ||||
| Operation range, (n%) | 0.351 | 0.778 | 0.037 | |||||
| Non-anatomical resection | 37 (39.4) | 37 (43.5) | 0.085 | 26 (40.0) | 30 (46.2) | 0.126 | ||
|
Hepatic segmentectomy (≤ 2 segments) |
30 (31.9) | 19 (22.4) | 0.205 | 19 (29.2) | 17 (26.1) | 0.068 | ||
|
Major resection (≥ 3 segments) |
27 (28.7) | 29 (34.1) | 0.119 | 20 (30.8) | 18 (27.7) | 0.067 | ||
Data are presented as mean ± standard deviation or number (percentage), as appropriate
PSM propensity score matching, ERAS enhanced recovery after surgery, SMD standardized mean difference, BMI Body Mass Index, ECOG-PS Eastern Cooperative Oncology Group Performance Status, ASA American Society of Anesthesiologists, AFP Alpha-fetoprotein concentration, HBsAg Hepatitis B surface antigen
Table 3 presents intraoperative and postoperative variables after PSM. The two groups did not differ significantly in operative time, intraoperative blood loss, or 30‑day readmission rates. In the ERAS group, one patient was readmitted for postoperative fever, whereas in the conventional care group, four were readmitted—one for pleural effusion, two for postoperative fever, and one for biliary fistula. Nasogastric tubes were used in 89.2% of patients in the conventional care group.
Table 3.
Intraoperative and postoperative outcomes after propensity score matching
| ERAS(n = 65) | Conventional care(n = 65) | Effect measure | Effect estimate(95%CI) | p value | |
|---|---|---|---|---|---|
| Operative time (min) | 195 (157,226) | 183 (153,227) | Median difference | 12 (-31 to 36) | 0.830 |
| Blood loss (mL) | 270 (240,320) | 300 (240,350) | Median difference | -30 (-50 to 20) | 0.077 |
| Nasogastric tube, n (%) | 7 (10.8) | 58 (89.2) | Odds ratio | 0.014 (0.00-0.04) | < 0.001 |
| Duration till first flatus (h) | 41 (27,53) | 61 (47,74) | Median difference | -20 (-28 to -9) | < 0.001 |
| Duration of urinary drainage (days) | 1 (1,2) | 2 (2,3) | Median difference | -1 (-1 to -1) | < 0.001 |
| Time until fluid diet (h) | 11.0 (9.0, 13.0) | 22.0 (20.0, 23.0) | Median difference | -11 (-12 to -10) | < 0.001 |
| Postoperative LOS (days) | 8 (5,10) | 10 (9,13) | Median difference | -2 (-4 to -1) | < 0.001 |
| Hospitalization costs adjusted to 2024 (CNY) |
38,188 (31842,44153) |
43,595 (36621,51427) |
Median difference | -6115 (-9519 to -2636) | < 0.001 |
| Readmission to hospital | 1 (1.5) | 4 (6.2) | Odds ratio | 0.24 (0.03 to 2.19) | 0.365 |
Effect estimates are presented as ERAS vs. conventional care. Continuous variables are expressed as mean ± standard deviation for normally distributed data and as median (interquartile range) or median (range) for skewed data. Categorical variables are expressed as number (percentage)
Bold values indicate the significant p values (p < 0.05)
ERAS Enhanced Recovery After Surgery, LOS length of stay
Compared with the conventional care group, the ERAS group achieved significantly earlier postoperative milestones: median time to first flatus ERAS: 41 h (IQR 27–53) vs. conventional care: 61 h (IQR 47–74); p < 0.001, median time to initiation of liquid diet 11.0 h (IQR 9.0–13.0) vs. 22.0 h (IQR 20.0–23.0); p < 0.001, and median urinary catheter retention 1 day (IQR 1–7) vs. 2 days (IQR 1–7); p < 0.001. The median postoperative LOS was also shorter in the ERAS group 8 days (IQR 5–10) vs. 10 days (IQR 9–13); p < 0.001. Approximately half of the ERAS patients were discharged by POD 8, whereas half of the conventional care group were discharged around POD 10. Furthermore, median CPI-adjusted hospitalization costs were significantly lower in the ERAS group 38,188 CNY (IQR 31842,44153) vs. 43,595 CNY (IQR 36621,51427); p < 0.001.
Postoperative pain outcomes are summarized in Table 4. On POD 1, the ERAS group had lower mean VAS scores than the conventional care group (3.0 ± 1.8 vs. 3.8 ± 1.6; p = 0.013), with fewer patients experiencing severe pain (21.5% vs. 46.2%; p = 0.003). On POD 3, pain scores remained lower in the ERAS group (2.0 ± 1.2 vs. 2.6 ± 1.6; p = 0.029), with severe pain reported less frequently (p = 0.039). No statistically significant difference in pain scores was observed on POD 5.
Table 4.
Postoperative pain scores after propensity score matching
| ERAS(n = 65) | Conventional care(n = 65) | Effect measure | Effect estimate(95%CI) | p value | |
|---|---|---|---|---|---|
| POD 1 (No. of patients) | 65 | 65 | |||
| VAS score | 3.0 ± 1.8 | 3.8 ± 1.6 | Mean difference | -0.76 (-1.37 to -0.16) | 0.013 |
| No. of patients (VAS ≥ 4) | 14 (21.5) | 30 (46.2) | Odds ratio | 0.32 (0.15 to 0.69) | 0.003 |
| POD 3 (No. of patients) | 65 | 65 | |||
| VAS score | 2.0 ± 1.2 | 2.6 ± 1.6 | Mean difference | -0.55 (-1.04 to -0.06) | 0.029 |
| No. of patients (VAS ≥ 4) | 7 (10.8) | 16 (24.6) | Odds ratio | 0.37 (0.14 to 0.97) | 0.039 |
| POD 5 (No. of patients) | 54 | 61 | |||
| VAS score | 1.7 ± 1.2 | 1.7 ± 0.9 | Mean difference | 0.08 (-0.33 to 0.48) | 0.705 |
| No. of patients (VAS ≥ 4) | 5 (9.3) | 1 (1.6) | Odds ratio | 6.53 (0.74 to 57.7) | 0.055 |
Data are presented as mean ± standard deviation or number (percentage), as appropriate
Bold values indicate the significant p values (p < 0.05)
ERAS enhanced recovery after surgery, VAS visual analogue scale, POD postoperative day
Table 5 details the most severe postoperative complications after PSM using the Clavien–Dindo classification. The overall complication rate was significantly lower in the ERAS group compared with the conventional care group (42 vs. 61; p < 0.001). Grades II complications were markedly reduced in the ERAS group (12 vs. 23; p = 0.047), whereas rates of Grade I and III complications were similar between groups.
Table 5.
Postoperative complications after propensity score matching according to the Clavien–Dindo classification
| Complications | ERAS (n = 65) |
Conventional care (n = 65) |
p value |
|---|---|---|---|
| Total | 42 | 61 | < 0.001 a |
| Grade I | 20 | 27 | 0.273a |
| Grade II | 12 | 23 | 0.047 a |
| Grade IIIa | 8 | 10 | 0.800a |
| Grade IIIb | 2 | 1 | 1.000b |
| Grade IV | 0 | 0 | NA |
| Grade V | 0 | 0 | NA |
Bold values indicate the significant p values (p < 0.05)
ERAS enhanced recovery after surgery
a Pearson χ2 test; b Fisher’s exact test
Major complications and their distribution are shown in Table 6. The ERAS group experienced lower incidences of nausea/vomiting (4 vs. 16; p = 0.006). No significant differences were observed for other complications.
Table 6.
Types of postoperative complications in the overall cohort
| Variables | ERAS (n = 65) | Conventional care (n = 65) | p value |
|---|---|---|---|
| Wound infection | 5 | 4 | 1.000b |
| Nausea/vomiting | 4 | 16 | 0.006 b |
| Deep venous thrombosis | 3 | 4 | 1.000b |
| Pleural effusion (Grade II) | 2 | 9 | 0.054b |
| Seroperitoneum (Grade II) | 2 | 7 | 0.164b |
| Atelectasis | 1 | 1 | 1.000b |
| Abdominal abscess | 2 | 2 | 1.000b |
| Pleural effusion (Grade IIIa) | 3 | 3 | 1.000b |
| Seroperitoneum (Grade IIIa) | 2 | 3 | 1.000b |
| Pulmonary embolism | 1 | 1 | 1.000b |
| Gastroparesis | 3 | 2 | 1.000b |
| Bile leak | 1 | 2 | 1.000b |
| Liver failure | 1 | 1 | 1.000b |
| Hemorrhage and reoperation | 1 | 1 | 1.000b |
| Other minor | 8 | 10 | 0.122a |
Bold values indicate the significant p values (p < 0.05)
ERAS enhanced recovery after surgery
a Pearson χ2 test; b Fisher’s exact test
An exploratory subgroup analysis according to the extent of hepatectomy is shown in Supplementary Table S2. In both the minor and major hepatectomy subgroups, the ERAS group generally showed faster postoperative recovery than the conventional care group, including earlier initiation of liquid diet, shorter urinary catheter retention, earlier first flatus, shorter postoperative LOS, and lower pain score on POD 1. These findings were generally consistent with the primary analysis.
Table 7 summarizes adherence to the 21 key elements of the ERAS protocol, which were developed based on recent ERAS Society recommendations for liver surgery. Overall adherence to most ERAS components was high. However, seven patients initially managed under the ERAS pathway did not fully adhere to all ERAS components. Among them, four patients required unplanned postoperative ICU transfer, one patient developed postoperative gastroparesis with intolerance to early oral intake and deep venous thrombosis complicated by pulmonary embolism requiring strict bed rest, and two patients refused early oral intake and early mobilization and requested withdrawal from the ERAS pathway. These patients were retained in the ERAS group in the intention-to-treat sensitivity analysis.
Table 7.
Compliance with 21 ERAS elements for liver resection based on recent recommendations
| ERAS (n = 94) |
||
|---|---|---|
| Element present | No. who followed element | |
| Routine dedicated preoperative counseling and education before liver surgery | Yes | 94 |
| Preop. nutrition | Yes | 86 |
| Preop. carbohydrate drink up to 2 h before surgery | Yes | 90 |
| Avoid oral bowel preparation | Yes | 87 |
| Pre-anesthetic medication (avoid long-acting anxiolytics) | Yes | 92 |
| Anti-thrombotic prophylaxis | Yes | 94 |
| Perioperative steroids administration | Yes | 84 |
| Antimicrobial prophylaxis and skin preparation | Yes | 94 |
| Minimally invasive surgical approach | Yes | 94 |
| Avoid nasogastric tube | Yes | 87 |
| Preventing intraoperative hypothermia | Yes | 94 |
| Postoperative nutrition and early oral intake | Yes | 84 |
| Postoperative glycaemic control | Yes | 94 |
| Prevention of delayed gastric emptying | Yes | 90 |
| Urinary catheter: 1–2 days only | Yes | 76 |
| Stimulation of bowel movement | Yes | 88 |
| Early mobilization | Yes | 87 |
| Multimodal analgesia | Yes | 90 |
| Preventing postoperative nausea and vomiting | Yes | 94 |
| Fluid management | Yes | 94 |
| Audit | Yes | 94 |
ERAS Enhanced Recovery After Surgery
The main affected ERAS components were early oral intake, early mobilization, and ward-based postoperative recovery. In addition, early urinary catheter removal was not achieved in all patients, mainly because of the high prevalence of benign prostatic hyperplasia among elderly male patients; 74 patients achieved early urinary catheter removal. Despite these deviations, the overall adherence pattern suggested that the ERAS pathway was feasible in most elderly patients undergoing laparoscopic hepatectomy.
Discussion
The present study provides focused evidence on ERAS implementation in elderly patients with HCC undergoing laparoscopic hepatectomy, a clinically important population that remains underrepresented in ERAS liver surgery research. After PSM, ERAS was associated with faster postoperative recovery, shorter postoperative LOS, lower pain scores, fewer postoperative complications, and reduced hospitalization costs, without increasing severe complications or 30-day readmissions. Exploratory subgroup analysis further showed that the direction of these benefits was generally consistent in both minor and major hepatectomy subgroups, suggesting that structured and individualized ERAS may be applicable across different extents of laparoscopic liver resection in carefully selected elderly patients with HCC.
These findings extend previous evidence that ERAS programs can accelerate recovery and reduce complications after liver surgery [19]. Unlike broader hepatectomy cohorts, elderly patients with HCC often have reduced physiological reserve, multiple comorbidities, chronic liver disease, and cirrhosis-related manifestations such as hypoalbuminemia, portal hypertension, and thrombocytopenia [29–31]. Existing ERAS studies in elderly liver surgery populations are limited and often include heterogeneous diseases and operative approaches [32, 33]. By focusing on elderly patients aged 70–85 years undergoing laparoscopic hepatectomy for HCC, our study adds disease- and age-specific evidence for the feasibility of ERAS in this vulnerable surgical population.
Our study protocol was aligned with the ERAS Society guidelines for liver surgery, which advocate a multimodal, evidence-based perioperative care strategy including early mobilization, early oral intake, multimodal analgesia, and meticulous fluid management [34]. Previous meta‑analyses have shown that ERAS can reduce postoperative LOS by 2–3 days and decrease postoperative complications by 25–30%, without negatively affecting mortality rates [35–37]. Consistent with these findings, our cohort showed a shorter postoperative LOS and a 29% reduction in overall complication rate in the ERAS group compared with controls, with no life-threatening (Clavien–Dindo grade IV–V) complications observed. These results reinforce the potential clinical value of ERAS in elderly patients undergoing laparoscopic liver surgery and highlight its ability to improve recovery while optimizing healthcare resource utilization.
From a pathophysiological standpoint, elderly patients generally have reduced cardiopulmonary reserve and impaired metabolic adaptation to surgical stress [38]. Therefore, minimizing operative stress—by avoiding prolonged preoperative fasting, promoting early mobilization, and preventing fluid overload—may be particularly beneficial in this population. Within the ERAS framework, comprehensive preoperative education, psychological counseling, and individualized perioperative planning can help reduce anxiety and improve patient engagement, thereby alleviating psychological stress during the perioperative period. Excessive preoperative fasting can intensify thirst, anxiety, and insulin resistance; conversely, shortened fasting periods and preoperative carbohydrate loading can help maintain metabolic stability and improve perioperative comfort, safety, and tolerance [39, 40]. In our ERAS cohort, these measures may have contributed to better overall tolerance of surgery and smoother postoperative recovery.
Prolonged postoperative bed rest in elderly patients can result in muscle strength decline, impaired lung function, reduced antioxidant capacity, and increased venous stasis and thrombus formation [41]. Accordingly, in our study, ERAS patients were encouraged to mobilize early using a graded regimen of sitting on the edge of the bed, then sitting, and standing before walking. All patients successfully completed this regimen, suggesting that early mobilization is feasible and beneficial for elderly patients. Early mobilization, combined with effective pain control and respiratory exercises, likely contributed to the lower incidence of pulmonary complications and pleural effusion observed in the ERAS group.
After hepatectomy, impaired liver function increases the risk of ascites, pleural effusion, and renal dysfunction, making appropriate perioperative fluid therapy essential [42]. In elderly individuals, reduced cardiac and renal reserve predisposes them to fluid overload and pulmonary congestion, which can in turn increase morbidity and mortality [43]. A large retrospective study demonstrated that restrictive perioperative fluid management was associated with improved outcomes in liver surgery patients, although hypovolemia must be avoided [44]. In our ERAS group, intraoperative goal-directed fluid therapy and careful postoperative fluid management likely contributed to better hemodynamic stability, lower rates of ascites and pleural effusion, and a reduction in postoperative LOS [45, 46]. These findings support the use of individualized, goal-directed fluid strategies as a core component of ERAS pathways in elderly patients undergoing hepatectomy.
Gastrointestinal functional recovery is another key element of postoperative outcomes. In our study, the ERAS group achieved earlier time to first flatus and earlier resumption of a liquid diet than the conventional group, consistent with randomized trials in hepatic resection [22]. These benefits are likely attributable to early feeding initiation and reduced opioid use, both of which promote faster gastrointestinal recovery [47–49]. Furthermore, multimodal opioid-sparing analgesia reduced opioid-related adverse effects, including nausea, vomiting, and delayed bowel function [39]. Specifically, intraoperative incision infiltration anesthesia combined with non-opioid analgesics provided effective pain control while minimizing exposure to strong opioids. Consequently, ERAS patients reported lower VAS scores, experienced less discomfort, and had fewer episodes of nausea and vomiting than those in the conventional group.
Elderly patients are particularly susceptible to postoperative pulmonary complications because of diminished respiratory reserve, a higher prevalence of chronic lung disease, anesthesia-related airway interventions, and prolonged bed rest [50]. After liver cancer surgery, diaphragmatic irritation can provoke pleural inflammation and impair lymphatic drainage, thereby predisposing patients to pleural effusion. Moreover, cirrhosis, portal hypertension, and postoperative hypoalbuminemia may further exacerbate this risk. In our cohort, targeted ERAS measures—such as early mobilization, effective pain control, respiratory training, and careful fluid management—were associated with a significantly lower incidence of pleural effusion, without an increase in severe respiratory events. These findings suggest that ERAS may help mitigate pulmonary risk in elderly patients after laparoscopic hepatectomy.
We also adapted certain ERAS components to individual patient needs. For example, in patients with benign prostatic hyperplasia, urinary catheter removal was postponed; in those with a history of abdominal surgery or severe gastrointestinal dysfunction, nasogastric decompression and modified feeding regimens were used. This individualized approach aligns with prior evidence highlighting the importance of patient-specific ERAS modification to optimize both safety and efficacy [51, 52]. Our experience indicates that strict adherence to every ERAS element is not always necessary; instead, a flexible, patient-centered application of ERAS principles may be more appropriate in frail elderly patients.
Beyond clinical benefits, ERAS implementation significantly reduced total hospitalization costs, likely due to shorter LOS, faster recovery, and fewer interventions for complications. Considering the aging trend among patients with liver cancer and the increasing burden on healthcare systems, broader adoption of ERAS protocols in appropriately selected elderly patients could yield substantial economic advantages.
This study has several limitations. First, it was a retrospective, single-center study conducted in an eastern Chinese tertiary hospital; therefore, residual confounding from unmeasured variables cannot be excluded despite PSM and the intention-to-treat sensitivity analysis, and external validity may be limited by differences in patient populations, perioperative resources, reimbursement policies, and hospital settings. Second, the before-and-after design may be affected by temporal changes in surgical technique, anesthesia, perioperative nursing, hospital infrastructure, and discharge practice. Although hospitalization costs were standardized to 2024 CNY using the annual CPI, the cost analysis remains institution-specific and should be interpreted cautiously when extrapolated to other healthcare systems. Third, the matched sample size was modest, which may have limited the power to detect differences in some secondary endpoints and made the subgroup analysis by extent of hepatectomy exploratory, especially for major hepatectomy. Fourth, only short-term perioperative outcomes were assessed; long-term oncologic outcomes, quality of life, and functional recovery were not evaluated. Fifth, ERAS adherence was described but not quantified at the level of each component, and the use of intraoperative cell salvage was not systematically recorded, leaving the possibility of residual bias. Finally, patients older than 85 years were not included in the surgical cohort, so the findings should not be directly extrapolated to very elderly patients with different frailty profiles, treatment strategies, and perioperative risks. Prospective multicenter studies with larger and more diverse populations, systematic ERAS compliance monitoring, and extended follow-up are needed to validate these findings.
Conclusion
The findings of this study demonstrate that ERAS is safe and effective for elderly patients undergoing laparoscopic resection for HCC. Relative to conventional perioperative management, ERAS facilitates faster recovery, reduces postoperative complications, and lowers hospitalization costs. These results support the active inclusion of elderly patients in ERAS pathways and underscore the value of individualized perioperative strategies to optimize clinical outcomes in this expanding patient population.
Supplementary Information
Authors’ contributions
YTZ, JNH and YL contribute to the conception and design of the study, YTZ, KLP and JTZ contribute to analysis and interpretation of data, JNH and HZH contribute to drafting the article. YL and JNH evaluated the imaging data of the patients.
Funding
This research was supported by the Joint Funds of the National Natural Science Foundation of China (Grant No. U23A20458), Ningbo Top Medical and Health Research Program (Grant No. 2022010101), Zhejiang Provincial Natural Science Foundation (Grant No. Q23H030002), Key Medical Discipline of Ningbo (Grant No. 2026-A27), Zhejiang Provincial Natural Science Foundation of China (Grant No. LMS26H160011) and Ningbo Clinical Research Center for Digestive System Tumors (Grant No. 2019A21003).
Data availability
The datasets generated and/or analysed during the current study are not publicly available due to institutional and legal restrictions on sharing individual clinical data, but de-identified data are available from the corresponding author on reasonable request and with permission of the Ethics Committee of Ningbo No. 2 Hospital.
Ethics declarations
Ethics approval and consent to participate
The study protocol was approved by the Ethics Committee of Ningbo No. 2 Hospital (approval No. [PJ-NBEY-KY-2026-005-01]). All procedures involving human participants were performed in accordance with the Declaration of Helsinki and relevant national and institutional guidelines and regulations. Written informed consent for participation in the ERAS programme and for the use of anonymized clinical data for research purposes was obtained from all patients.
Consent for publication
This study does not contain any individual details, images or videos that could lead to the identification of a participant. Therefore, consent for publication is not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Jingna Hu and Huzhe Zhu contributed equally to this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets generated and/or analysed during the current study are not publicly available due to institutional and legal restrictions on sharing individual clinical data, but de-identified data are available from the corresponding author on reasonable request and with permission of the Ethics Committee of Ningbo No. 2 Hospital.