Short- and Long-Term Outcomes in Laparoscopic Versus Open Hepatectomy for Hepatocellular Carcinoma in Elderly Patients: A Systematic Review and Meta-Analysis

Abstract

Background:

Laparoscopic hepatectomy (LH) is considered a safe and feasible treatment for patients with hepatocellular carcinoma (HCC) in recent studies. However, in elderly patients, application of LH still remains controversial, and the outcomes of LH versus open hepatectomy (OH) have not been fully evaluated. Our objective is to compare the short- and long-term outcomes of LH with OH in elderly patients with HCC.

Materials and Methods:

All studies comparing LH and OH in elderly patients with HCC were systematically searched in the databases of PubMed, EmBase, and Web of Science. Statistical analysis was conducted using Review Manager 5.3 (Cochrane Collaboration, 2014). The last search was performed on March 20, 2022. Short-term outcomes include blood loss, operation time, blood transfusion, overall and major postoperative complications, mortality, hospital stay, tumor size, and surgical margin. Long-term outcomes include 1-, 3-, and 5-year overall survival (OS); 1-, 3-, and 5-year disease-free survival (DFS); and 1-, 3-, and 5-year recurrence-free survival (RFS).

Results:

Fourteen studies involving 1596 patients were included in this meta-analysis. The short-term outcomes of LH were a shorter postoperative hospital stay and fewer overall and major postoperative complications (all P < .00001). However, there were no significant differences in operation time, blood loss, blood transfusion rate, surgical margin, tumor size, and mortality. For the long-term outcomes, LH is comparable with OH in terms of 1-, 3-, and 5-year OS; 1-, 3-, and 5-year DFS; and 1-, 3-, and 5-year RFS.

Conclusions:

Compared with OH, LH is a safe and feasible treatment for elderly patients with HCC.

Introduction

With the increase in life span of the elderly population, the incidence of diseases is increasing; 92 diseases were identified as age related.¹ From 2006 to 2016, cancer cases increased by 28% worldwide, and an aging population contributed 17% to this change.² Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related deaths.³

Population aging was one of the factors that increased the cases of liver cancer from 732,000 in 2006 to 1 million in 2016.² Although a declining incidence of HCC was observed in some countries in recent years, for elderly patients, the incidence is still increasing.⁴ Therefore, there is an urgent need for optimal management of elderly patients with HCC.

The treatment of HCC includes surgical resection, transplantation, ablation, transarterial chemoembolization, and tyrosine kinase inhibitors.⁵ For resectable cases, surgical resection is still a first-line curative treatment for HCC.⁶ For elderly patients, however, management of HCC is complex as no prospective studies and guidelines are currently available.

Controversies still remain regarding surgical liver resection for the elderly. First, elderly patients have more comorbidities, such as cardiovascular problems, diabetes mellitus, hypertension, and pulmonary diseases, which increase the risk of complications perioperatively.⁷ Second, the function and structure of the liver change and the regenerative ability of liver cells declines in the elderly.⁸ Third, life expectancy of the elderly is limited.

Considering these aspects, surgeons tend to adopt conservative treatments for elderly patients. In the past two decades, liver resection was applied in 12%–28% of young patients, while the range was 0%–14% in elderly patients⁹; this rate was underestimated for management of elderly patients with HCC. Nonetheless, from studies reported in recent years, elderly patients can also benefit from liver resection.^10,11

Since first described by Reich in 1991,¹² great progress has been made with laparoscopic hepatectomy (LH) in liver surgery in recent years. Compared with open hepatectomy (OH), LH shows encouraging outcomes perioperatively. However, potential disadvantages of laparoscopy have reduced the popularity of LH in elderly patients, such as the adverse effects of increased intra-abdominal pressure, incidence of postoperative complications, and uncertain prognosis of LH.^9,13 In view of these concerns, conservative opinions still remain regarding application of LH in elderly patients.

Although outcomes have been reported in some article reviews about LH in elderly patients,^14–17 the number of studies included were limited. Furthermore, besides HCC, tumors of other pathological types were also included in the literature, such as intrahepatic cholangiocarcinoma and metastatic tumor, which may result in different surgical outcomes; maybe for this reason, long-term outcomes were not evaluated in these studies. Therefore, the objective of our study is to evaluate the short- and long-term outcomes in elderly patients with HCC.

Materials and Methods

Ethical Statment

The research was completed in accordance with the Declaration of Helsinki revised in 2013.

Data sources and search strategy

This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).¹⁸ Searches were conducted in the databases of PubMed, EmBase, and Web of Science.

Combinations of the following key words were used for searching: “laparoscopic hepatectomy,” “laparoscopic liver resection,” “minimal invasive hepatectomy,” “minimal invasive liver resection,” “open hepatectomy,” “open liver resection,” “hepatocellular carcinoma,” “liver cancer,” “elderly patients,” and “aged patients.”

Reference lists of the selected studies and relevant systematic reviews were also checked to identify studies that met our inclusion criteria. The last search was performed on March 20, 2022.

Study selection

Two authors (S.J. and D.Y.) screened the identified studies independently. The final decision of included studies was made by consensus of the two authors. Inclusion criteria for this meta-analysis were as follows: (1) studies related to the comparison between LH and OH in elderly patients with HCC; (2) studies with age cutoff for elderly patients set at ≥65 years or most patients aged ≥65 years; (3) studies reporting at least one of the outcomes of interest; and (4) studies with language restricted to English.

The exclusion criteria were as follows: (1) studies with no control group; (2) nonhuman studies, reviews, letters, abstracts, editorials, or case reports; (3) studies comparing elderly and nonelderly patients; (4) studies including patients with benign lesions or other types of malignant liver tumors; and (5) studies on repeat liver resection for recurrent cases.

Data extraction

Data extraction was conducted by two authors (S.J. and D.Y.) independently, and any discrepancies were resolved through discussion. The data of baseline characteristics extracted include the first author, region, study design, period, age, number of patients, and conversion.

Outcomes of interest include blood loss; operation time; overall and major postoperative complications; transfusion rate; mortality; hospital stay; tumor size; surgical margin; 1-, 3-, and 5-year overall survival (OS); 1-, 3-, and 5-year disease-free survival (DFS); and 1-, 3-, and 5-year recurrence-free survival (RFS). Major complication was defined as Clavien–Dindo grade ≥III or extracted from studies when it was reported directly.

Quality assessment

Quality assessment of the included studies was based on the Newcastle–Ottawa Scale (NOS), which consists of three sections: patient selection, comparability of the study, and assessment of the outcome. The total score ranged from 0 to 9. Studies with cumulative scores ≥7 were denoted as high-quality studies.

Statistical analyses

All statistical analyses were conducted using Review Manager 5.3 (Cochrane Collaboration, 2014). Continuous outcomes are expressed as medians and ranges or medians and interquartile ranges were converted to means and standard variances based on the method by Hozo et al.¹⁹ Odds risk (OR) and weighted mean difference (WMD) were used for dichotomous and continuous variables, respectively; 95% confidence intervals (CIs) are reported for all results.

Heterogeneity was assessed using the value of the chi-square test and I^{2 .}test. P < .10 and I² > 50% represent the existence of significant heterogeneity among studies, and a random-effects model was applied for the data analysis. Otherwise, a fixed-effect model was used. Statistical significance for comparison was set at P < .05. The subgroup analysis was performed according to matched and nonmatched studies.

A sensitivity analysis was conducted to explore potential sources of heterogeneity by excluding one study in each turn to evaluate the effect on the overall pooled results. A funnel plot was used to assess publication bias.

Results

Study selection and characteristics

The study search strategies and results are shown in Figure 1. A total of 3249 studies were found in the primary literature search. After removing 2174 duplicates, 1075 articles were assessed by screening the titles and abstracts. Then, 1040 articles were excluded due to irrelevance. For the remaining 35 studies, 21 full-text studies were further removed according to our exclusion criteria.

FIG. 1.

Flowchart of study inclusion.

Finally, 14 studies^20–33 published between 2001 and 2022 met our inclusion criteria. Twelve studies were matched and two were nonmatched. In these studies, the age cutoff for elderly patients was set at ≥75 years (n = 2),^20,27 ≥70 years (n = 5),^21–24,29 and ≥65 years (n = 2).^26,33 Five studies did not target elderly patients; however, the minimum age of patients was over 65 years in one study,³¹ and in the other four studies,^25,28,30,32 the mean age was >65 years, with small ranges or standard deviations, so most of the patients evaluated were over 65 years of age.

There were 1569 patients in total, 744 patients were in the laparoscopic group and 825 patients in the open group. The rate of conversion ranged from 0% to 28.1%. The baseline characteristics of included studies are presented in Table 1.

Table 1.

Baseline Characteristics of Included Studies

Study	Region	Study design	Period	Age, years, (LH/OH)		No. of patients		Conversion, n (%)	NOS
Study	Region	Study design	Period	LH	OH	LH	OH	Conversion, n (%)	NOS
Amato et al. (2017)²⁰	Italy	R	2010–2014	77 ± 1.6^b	78 ± 1.9^b	11	18	NA	6
Chen et al. (2020)²¹	China	MR	2013–2018	71 (70–77)^a	72 (70–76)^a	64	64	0	8
Dumronggittigule et al. (2020)²²	Korea	MR	2003–2018	73 (71–79)^c	73 (71–75)^c	41	41	5 (12.2)	8
Delvecchio et al. (2021)²³	Italy	MR	2009–2019	74.3 (70–86)^a	75 (70–82)^a	38	84	NA	7
Goh et al. (2018)²⁴	Singapore	MR	2007–2016	73 (70–88)^a	74.5 (70–83)^a	32	32	9 (28.1)	7
Harada et al. (2016)²⁵	Japan	R	2008–2015	74 ± 6^b	70 ± 7^b	20	48	NA	8
Kim et al. (2020)²⁶	Korea	MR	2013–2017	69 (65–84)^a	70 (65–82)^a	91	91	NA	7
Nomi et al. (2020)²⁷	Japan	MR	2010–2017	78 (75–93)^a	78 (75–87)^a	155	155	11 (7.1)	7
Noda et al. (2018)²⁸	Japan	MR	2001–2015	71.0 ± 8.8^b	71.9 ± 6.3^b	18	18	NA	7
Monden et al. (2022)²⁹	Japan	MR	2010–2021	75 (70–83)^a	75 (70–90)^a	75	75	0	7
Sandro et al. (2018)³⁰	Italy	MR	2005–2017	68.6 (61.3–75.5)^c	67.1 (61.2–75)^c	75	75	6 (7.6)	7
Tanaka et al. (2015)³¹	Japan	MR	2007–2014	70 (66–73)^d	71 (67–75)^d	20	20	0	7
Untereiner et al. (2019)³²	France	MR	2012–2017	68.3 (61.0–73.2)^c	65.3 (64.3–71.5)^c	33	33	2 (6.1)	7
Wen et al. (2021)³³	China	MR	2015–2018	68 (66–72)^a	69 (66–72)^a	71	71	NA	8

Median(range).

Mean ± SD.

Median (IQR).

Mean (95% CI).

CI, confidence interval; IQR, interquartile range; MR, matched retrospective; NA, not available; NOS, Newcastle–Ottawa Scale; R, retrospective.

Short-term outcomes

The operation time was reported in 13 studies.^{20–26,28–33} Pooled data suggested that there was no significant difference between the two groups (1259 patients, WMD = 8.86, 95% CI = −11.12 to 28.83, P = .38, Fig. 2a), and similar results can be observed in both matched and nonmatched studies. In addition, there remained a significant degree of heterogeneity (I² = 88%, P < .00001).

FIG. 2.

Forest plots and subgroup meta-analysis of the operation time (a), blood loss (b), surgical margin (c), and tumor size (d).

Thirteen studies^{20–22,24–33} reported blood loss, which revealed that there was no statistically significant difference in blood loss between LH and OH groups (1447 patients, WMD = −34.22, 95% CI = −146.61 to 78.18, P = .55, Fig. 2b), although nonmatched studies suggested less blood loss in the LH group; only two studies were included. Heterogeneity among the studies was high (I² = 95%, P < .00001).

The surgical margin was evaluated in six studies.^{21,24,26,30,31,33} The pooled data were all from matched studies, and there was no significant difference between the two groups (706 patients, WMD = −0.18, 95% CI = −0.60 to 0.25, P = .41, Fig. 2c). Heterogeneity was also high among studies (I² = 95%, P < .00001).

The tumor size was reported in 13 studies.^20,22–33 Pooled data suggested that there was no significant difference in tumor size between the two groups (1441 patients, WMD = −0.14, 95% CI = −0.28 to 0.01, P = .06, Fig. 2d), and there was low heterogeneity among the studies (I² = 47%, P = .03), although the nonmatched group revealed a smaller tumor size in the LH group; only two studies were included.

There were 10 studies that reported on blood transfusion.^{22–27,29,30,32,33} No significant difference was observed in blood transfusion between the two groups (1336 patients, OR = 0.67, 95% CI = 0.40–1.12, P = .12, Fig. 3a).

FIG. 3.

Forest plots and subgroup meta-analysis of blood transfusion (a), overall postoperative complications (b), major postoperative complications (c), mortality (d), and postoperative hospital stay (e).

Twelve studies reported overall postoperative complications.^{20–25,27,28,30–33} The result showed that there were fewer overall postoperative complications in the LH group (1237 patients, OR = 0.38, 95% CI = 0.29–0.49, P < .00001, Fig. 3b), and the subgroup analysis also presented a similar result.

Twelve studies reported major postoperative complications.^{20–25,27,29–33} The result showed that there were fewer major postoperative complications in the LH group (1351 patients, OR = 0.40, 95% CI = 0.28–0.58, P < .00001, Fig. 3c), although a different result was observed in nonmatched studies; there were only two studies in this group.

Mortality was reported in 13 studies.^{20–27,29–33} The outcome suggested that there was no significant difference between the two groups in mortality (1533 patients, OR = 0.48, 95% CI = 0.21–1.12, P = .09, Fig. 3d).

The duration of hospital stay was reported in 14 studies.^20–33 Patients in the laparoscopic group had a shorter postoperative hospital stay (1569 patients, WMD = −14.74, 95% CI = −18.04 to −11.44, P < .00001, Fig. 3e), although a significant statistical difference was not observed in nonmatched studies. In addition, there also remains a significant degree of heterogeneity among the studies (I² = 98%, P < .00001).

Long-term outcomes

For long-term outcomes, pooled data revealed that there were no statistical differences in 1-year OS^{22,23,26,28,31} (462 patients, OR = 1.02, 95% CI = 0.37 to 2.81, P = .97, Fig. 4a), 3-year OS^{22,23,26,28,30–32} (678 patients, OR = 1.41, 95% CI = 0.89 to 2.24, P = .14, Fig. 4b), 5-year OS^{21–23,26,28,31} (590 patients, OR = 1.19, 95% CI = 0.80–1.78, P = .38, Fig. 4c), 1-year DFS^23,26,28,31 (380 patients, OR = 0.69, 95% CI = 0.42–1.13, P = .14, Fig. 4d), 3-year DFS^23,26,28,31 (380 patients, OR = 0.92, 95% CI = 0.59–1.41, P = .69, Fig. 4e), 5-year DFS^21,23,26,28 (468 patients, OR = 0.70, 95% CI = 0.48–1.02, P = .07, Fig. 4f), 1-year RFS^22,25 (150 patients, OR = 1.15, 95% CI = 0.53–2.49, P = .72, Fig. 4g), 3-year RFS^22,25,30,32 (366 patients, OR = 1.06, 95% CI = 0.69–1.61, P = .80, Fig. 4h), and 5-year RFS^22,25 (150 patients, OR = 1.01, 95% CI = 0.34–3.02, P = .98, Fig. 4i) between the LH and OH groups.

FIG. 4.

Forest plots of 1-year OS (a), 3-year OS (b), and 5-year OS (c); 1-year DFS (d), 3-year DFS (e), and 5-year DFS (f); and 1-year RFS (g), 3-year RFS (h), and 5-year RFS (i). DFS, disease-free survival; OS, overall survival; RFS, recurrence-free survival.

Sensitivity analysis, publication bias, and subgroup analysis

A sensitivity analysis was conducted by excluding one study in each turn to evaluate the effect on the overall pooled results; however, the heterogeneity was not substantially reduced.

Publication bias was evaluated based on funnel plots of perioperative outcomes (Fig. 5). There was no evidence of bias for operation time, blood loss, tumor size, overall complications, major complications, and mortality. However, the funnel plot for hospital stay showed some degree of bias, which may be due to different discharge criteria between centers.

FIG. 5.

The funnel plot of operation time (a), blood loss (b), tumor size (c), blood transfusion (d), overall postoperative complications (e), major postoperative complications (f), mortality (g), and hospital stay (h).

The subgroup analysis was based on matched and nonmatched studies. We found that the pooled outcomes of matched studies were in line with that of total pooled outcomes. However, in the nonmatched group, less blood loss, smaller tumor size, and no statistical differences in severe complications and hospital stay were reported for LH. Considering the limited studies included in the nonmatched group, these outcomes should be interpreted with caution.

Discussion

Aging is associated with increased oxidative stress, heightened inflammatory response, and deteriorating immunity.³⁴ The structure and function of the liver change gradually with aging, such as decrease in liver mass and hepatic blood flow and dysfunction in synthesis and metabolism of liver cells.³⁵ The generation capacity of liver cells weakens and recovery of liver function is delayed when exposed to injuries.^8,36

Meanwhile, comorbidities increase in this process. In addition, considering the limited life expectancy, liver resection in elderly patients remains controversial. Therefore, we conducted this review and meta-analysis to evaluate the safety and feasibility of LH for HCC in elderly patients.

With development of laparoscopic equipment and accumulation of surgeons' experience, LH has achieved great progress and shown encouraging results perioperatively, such as the tendency toward decrease in blood loss, conversion rate, and complications.^37,38 A longer operation time was reported for LH in the beginning.³⁹

However, a comparable operation time between LH and OH has been presented in recent years.^14–16 Tsai et al reported a shorter operation time for LH in their study. However, it was only observed in cases with early TNM stage of HCC.⁴⁰ In our study, a significant difference in operation time was not found between the two groups.

Actually, the outcome of operation time was not consistent among studies comparing LH with OH. This may be due to differences in the range of resection, location of tumor, learning curve, center volumes, and surgeons' experience, especially the range of liver resection. A shorter operation time for LH was observed in partial resection of the liver, whereas in the case of major liver resection, LH is not superior to OH in operation time.^41,42

Hemorrhage is one of the main reasons for conversion in LH.⁴³ Considering the abundant blood supply in the liver, efficacious control of bleeding is key to the success of LH. Studies found that blood loss and transfusion were associated with increased postoperative complications and had a negative impact on long-term prognosis of patients undergoing hepatectomy.^44–46

LH is considered with the advantages of bleeding control in some aspects, such as the hemostatic effect of high intraperitoneal pressure caused by carbon dioxide, high clarity, and magnified effect of laparoscopy, which allowed surgeons to better identify intrahepatic blood vessels.^39,47,48 The development of laparoscopic devices in stanching bleeding may also play an important role in controlling bleeding. Less blood loss and a lower transfusion rate were reported in studies in recent years.^14,16,17,49

However, in our study, blood loss and transfusion rates showed no significant difference between the two groups. It is worth noting that blood loss in LH may be underestimated. Studies indicated that traditional means of calculating blood loss by summing up the intraoperation suction fluid and gauze weight values may be inaccurate, as fluids cannot be suctioned fully because of the limited workspace in LH. On calculating the blood volume and change in hematocrit levels, there was no evidence in favor of LH for less blood loss than OH.^50,51

To avoid touching the tumor, achieving a safe surgical margin in the condition of laparoscopic surgery was once a matter of concern. In line with previous studies, laparoscopic techniques have achieved surgical margins that are comparable with those of open liver resection.^48,52 Enough surgical margin can be obtained by laparoscopic ultrasonic and imaging assessment perioperatively, such as indocyanine green fluorescence imaging.⁵³

A study revealed that patients with smaller tumor size were more likely to be submitted to LH⁵⁴; in our literature, however, a significant difference was not found in tumor size, and with low heterogeneity among studies, this may be because most of the studies included in our study were matched.

A published study showed that mortality and morbidity rates were 0%–42.9% and 9%–51%, respectively, in elderly patients with HCC after hepatectomy.⁵⁵ Although complications were considered more common in elderly patients, especially severe complications after traditional liver resection,⁷ studies and meta-analyses have shown a comparable and even declining incidence of complications in recent years, especially with the laparoscopic approach.^14–16,56

Similarly, our study showed that LH achieved not only fewer overall complications but also fewer major complications, with no statistical difference in mortality. This may be attributed to advances in perioperative management and advantages of laparoscopic surgery, such as a smaller incision and reduced inflammatory and stress responses.⁵⁷

Just as many previous studies have reported, the hospital stay was shorter in the LH group in our study. This was apart from less invasiveness, reduced pain, early recovery of gastrointestinal function, and fewer postoperative complications with LH.^52,58,59

The prognosis of LH is still uncertain. Studies have found comparable long-term prognosis with OH and LH in patients with HCC.^54,60,61 In addition, some studies indicate that LH may potentially provide better prognosis.^62,63 Compared with the traditional open approach, laparoscopic surgery has the advantages of decreasing circulating tumor cells, perioperative stress, and manipulation of the tumor, which have positive effects of reducing the risk of tumor growth, recurrence, and metastasis.^64–66

Age is one of the risk factors for the prognosis of HCC.⁹ Considering the incidence of postoperative complications and long-term prognosis, surgical liver resection in elderly patients was applied with caution. Comparisons between LH and OH in elderly patients have been reported in previous studies; however, the long-term outcomes of the two groups were not evaluated.^14–17

From studies reported in recent years, the prognosis of liver resection in elderly patients is found to be acceptable.^67,68 In our study, the pooled results indicated that there were no significant statistical differences in OS, DFS, and RFS between the two groups. Studies suggested that the prognosis of LH in elderly patients and younger patients also showed no significant difference.^69,70 Unfortunately, these studies are retrospective.

Furthermore, the prognosis can be influenced by pathological stage, vessel invasion, cirrhosis, tumor number, blood flow occlusion, and postoperative complications.^71,72 Thus, the outcomes of prognosis still need randomized controlled trials for further confirmation.

There are some limitations that should be acknowledged in our study. First, owing to the different levels of socioeconomic and medical development, the definition of elderly varied worldwide, ranging from 60 to 80 years of age.⁹ The cutoff used to define the age of elderly patients was different in the studies that we included, which may introduce bias and heterogeneity among studies.

Second, all of the studies included in our meta-analysis were retrospective; although most studies were matched, a randomized controlled trial was absent, and this may have led to some degree of selection bias.

Third, significant heterogeneity existed in the operation time, blood loss, hospital stay, and surgical margin; although we conducted sensitivity and subgroup analyses, significant reduction in heterogeneity was not observed. This may be due to the differences in hospital volumes, laparoscopy devices, definitions of outcomes, and different stages of learning curves for surgeons.

In conclusion, this study provides the evidence that compared with OH, elderly patients with HCC can benefit from LH with fewer postoperative complications and shorter hospital stay. Furthermore, the prognosis was comparable between the two methods. LH is safe and feasible for liver resection in elderly patients with HCC. Considering that the studies included are retrospective, randomized controlled trials are needed to confirm the results of our study.

Footnotes

Acknowledgment

The authors thank all the members in their department for their suggestions.

Authors' Contributions

S.J. was involved in conceptualization, data curation, formal analysis, investigation, and writing.

D.Y. was involved in data curation, formal analysis, and investigation.

H.H. was involved in methodology.

H.S. was involved in software.

Y.S. was involved in visualization.

L.Z. was involved in resources.

Z.W. was involved in supervision.

Q.G. was involved in project administration.

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Supplementary Material

References

Chang

, Skirbekk

, Tyrovolas

, et al. Measuring population ageing: An analysis of the Global Burden of Disease Study 2017. Lancet Public Health, 2019; 4:e159–e167; doi: 10.1016/S2468-2667(19)30019-2

Fitzmaurice

, Akinyemiju

, Al Lami

, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2016: A systematic analysis for the Global Burden of Disease Study. JAMA Oncol, 2018; 4:1553–1568; doi: 10.1001/jamaoncol.2018.2706

Freddie

Bray

, Jacques, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A cancer journal for clinicians. CA Cancer J Clin, 2018; 68:394–424; doi: 10.3322/caac.21492

Rich

, Yopp

, Singnal

, et al. Hepatocellular carcinoma incidence is decreasing among younger adults in the United States. Clin Gastroenterol Hepatology, 2020; 18:242–248; doi: 10.1016/j.cgh.2019.04.043

Forner

, Reig

, Bruix

. Hepatocullar carcinoma. Lancet, 2018; 391:1301–1314; doi: 10.1016/S0140-6736(18)30010-2

Llovet

, Zucman-Rossi

, Pikarsky

, et al. Hepatocellular carcinoma. Nat Rev Dis Primers, 2016; 2:16018; doi: 10.1038/nrdp.2016.18

Tzeng

, Cooper

, Vauthey

, et al. Predictors of morbidity and mortality after hepatectomy in elderly patients: Analysis of 7621 NSQIP patients. HPB (Oxford), 2014; 16:459–468; doi: 10.1111/hpb.12155

Timchenko

. Aging and liver regeneration. Trands Endocrinol Metab, 2009; 20:171–176; doi: 10.1016/j.tem.2009.01.005

Federico

, Giunta

, Pappalardo

, et al. How to treat hepatocellular carcinoma in elderly patients. Pharmaceuticals (Basel), 2021; 14:233; doi: 10.3390/ph14030233

10.

Rho

, Lee

, Kim

, et al. Current status of therapeutic choice and feasibility for patients with hepatocellular carcinoma aged ≥70 years: A Nationwide Cancer Registry analysis. J Hepatocell Carcinoma, 2021; 8:321–332; doi: 10.2147/JHC.S306507

11.

Xing

, Liang

, Wang

, et al. Multicenter analysis of long-term oncologic outcomes of hepatectomy for elderly patients with hepatocellular carcinoma. HPB (Oxford), 2020; 22:1314–1323; doi: 10.1016/j.hpb.2019.12.006

12.

Reich

, McGlynn

, DeCaprio

, et al. Laparoscopic excision of benign liver lesions. Obstet Gynecol, 1991; 78:956–958.

13.

López

, Cid

, Poves

, et al. Laparoscopic surgery in the elderly patient. Surg Endosc, 2003; 17:333–337; doi: 10.1007/s00464-002-9056-7

14.

Hildebrand

, Verkoulen

, Dewulf

, et al. Short-term outcomes of laparoscopic versus open hepatectomy in the elderly patient: Systematic review and meta-analysis. HPB (Oxford), 2021; 23:984–993; doi: 10.1016/j.hpb.2021.01.016

15.

Chen

, Pan

, Maher

, et al. Laparoscopic hepatectomy for elderly patients: Major findings based on a systematic review and meta-analysis. Medicine (Baltimore), 2018; 97:e11703; doi: 10.1097/MD.0000000000011703

16.

Mohamedahmed

AYY

, Zaman

, Albendary

, et al. Laparoscopic versus open hepatectomy for malignant liver tumours in the elderly: Systematic review and meta-analysis. Updates Surg, 2021; 73:1623–1641; doi: 10.1007/s13304-021-01091-7

17.

Notarnicola

, Felli

, Roselli

, et al. Laparoscopic liver resection in elderly patients: Systematic review and meta-analysis. Surg Endosc, 2019; 33:2763–2773; doi: 10.1007/s00464-019-06840-9

18.

Liberati

, Altman

, Tetzlaff

, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration. BMJ, 2009; 339:b2700. doi: 10.1136/bmj.b2700

19.

Hozo

, Djulbegovic

, Hozo

. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol, 2005; 5:13; doi: 10.1186/1471-2288-5-13

20.

Amato

, Aprea

, De Rosa

, et al. Laparoscopic hepatectomy for HCC in elderly patients: Risks and feasibility. Aging Clin Exp Res, 2017; 29 (Suppl 1):179–183; doi: 10.1007/s40520-016-0675-6

21.

Chen

, Yu

, Quan

. Laparoscopic versus open hepatectomy for elderly patients with hepatocellular carcinoma. J BUON, 2020; 25:1404–1412.

22.

Dumronggittigule

, Han

, Ahn

, et al. Laparoscopic versus open hepatectomy for hepatocellular carcinoma in elderly patients: A single-institutional propensity score matching comparison. Dig Surg, 2020; 37:495–504; doi: 10.1159/000510960

23.

Delvecchio

, Conticchio

, Ratti

, et al. Laparoscopic major hepatectomy for hepatocellular carcinoma in elderly patients: A multicentric propensity score-based analysis. Surg Endosc, 2021; 35:3642–3652; doi: 10.1007/s00464-020-07843-7

24.

Goh

BKP

, Chua

, Syn

, et al. Perioperative outcomes of laparoscopic minor hepatectomy for hepatocellular carcinoma in the elderly. World J Surg, 2018; 42:4063–4069; doi: 10.1007/s00268-018-4741-4

25.

Harada

, Maeda

, Yoshizumi

, et al. Laparoscopic liver resection is a feasible treatment for patients with hepatocellular carcinoma and portal hypertension. Anticancer Res, 2016; 36:3489–3497.

26.

Kim

, Kim

, Rhu

, et al. Elderly hepatocellular carcinoma patients: Open or laparoscopic approach?. Cancers (Basel), 2020; 12:2281; doi: 10.3390/cancers12082281

27.

Nomi

, Hirokawa

, Kaibori

, et al. Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: A multi-centre propensity score-based analysis. Surg Endosc, 2020; 34:658–666; doi: 10.1007/s00464-019-06812-z

28.

Noda

, Eguchi

, Iwagami

, et al. Minimally invasive liver resection for hepatocellular carcinoma of patients with liver damage B: A propensity score-based analysis. Hepatol Res, 2018; 48:539–548; doi: 10.1111/hepr.13057

29.

Monden

, Sadamori

, Hioki

, et al. Short-term outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma in older patients: A propensity score matching analysis. BMC Surg, 2022; 22:63; doi: 10.1186/s12893-022-01518-x

30.

Sandro

, Bagnardi

, Najjar

, et al. Minor laparoscopic liver resection for Hepatocellular Carcinoma is safer than minor open resection, especially for less compensated cirrhotic patients: Propensity score analysis. Surg Oncol, 2018; 27:722–729; doi: 10.1016/j.suronc.2018.10.001

31.

Tanaka

, Takemura

, Shinkawa

, et al. Outcomes of pure laparoscopic versus open hepatic resection for hepatocellular carcinoma in cirrhotic patients: A case-control study with propensity score matching. Eur Surg Res, 2015; 55:291–301; doi: 10.1159/000439274

32.

Untereiner

, Cagniet

, Memeo

, et al. Laparoscopic hepatectomy versus open hepatectomy for the management of hepatocellular carcinoma: A comparative study using a propensity score matching. World J Surg, 2019; 43:615–625; doi: 10.1007/s00268-018-4827-z

33.

Wen

, Liu

, Zhang

, et al. Laparoscopic liver resection for hepatocellular carcinoma presents less respiratory complications compared with open procedure: A propensity score analysis in the elderly. Eur J Surg Oncol, 2021; 47:2675–2681; doi: 10.1016/j.ejso.2021.04.032

34.

Poulose

, Raju

. Aging and injury: Alterations in cellular energetics and organ function. Aging Dis, 2014; 5:101–108; doi: 10.14336/AD.2014.0500101

35.

Schmucker

. Age-related changes in liver structure and function: Implications for disease?. Exp Gerontol, 2005; 40:650–659; doi: 10.1016/j.exger.2005.06.009

36.

Hoare

, Das

, Alexander

. Ageing, telomeres, senescence, and liver injury. J Hepatol, 2010; 53:950–961; doi: 10.1016/j.jhep.2010.06.009

37.

Berardi

, Van Cleven

, Fretland ÅA, et al. Evolution of laparoscopic liver surgery from innovation to implementation to mastery: Perioperative and oncologic outcomes of 2,238 patients from 4 European specialized centers. J Am Coll Surg, 2017; 225:639–649; doi: 10.1016/j.jamcollsurg.2017.08.006

38.

Kim

, Rhu

, Ha

, et al. Realization of improved outcomes following liver resection in hepatocellular carcinoma patients aged 75years and older. Ann Surg Treat Res, 2021; 101:257–265; doi: 10.4174/astr.2021.101.5.257

39.

Belli

, Fantini

, D'Agostino

, et al. Laparoscopic versus open liver resection for hepatocellular carcinoma in patients with histologically proven cirrhosis: Short- and middle-term results. Surg Endosc, 2007; 21:2004–2011; doi: 10.1007/s00464-007-9503-6

40.

Tsai

, Chen

, Wang

, et al. Long-term and short-term surgical outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma: Might laparoscopic approach be better in early HCC?. Surg Endosc, 2019; 33:1131–1139; doi: 10.1007/s00464-018-6372-0

41.

Kasai

, Cipriani

, Gayet

, et al. Laparoscopic versus open major hepatectomy: A systematic review and meta-analysis of individual patient data. Surgery, 2018; 163:985–995; doi: 10.1016/j.surg.2018.01.020

42.

Tozzi

, Berardi

, Vierstraete

, et al. Laparoscopic versus open approach for formal right and left hepatectomy: A propensity score matching analysis. World J Surg, 2018; 42:2627–2634; doi: 10.1007/s00268-018-4524-y

43.

Alkhalili

, Berber

. Laparoscopic liver resection for malignancy: A review of the literature. World J Gastroenterol, 2014; 20: 13599–13606; doi: 10.3748/wjg.v20.i37.13599

44.

Xun

, Tian

, Hu

, et al. The impact of perioperative allogeneic blood transfusion on prognosis of hepatocellular carcinoma after radical hepatectomy: A systematic review and meta-analysis of cohort studies. Medicine (Baltimore), 2018; 97:e12911; doi: 10.1097/MD.0000000000012911

45.

Martin

, Kerwin

, Turrentine

, et al. Blood transfusion is an independent predictor of morbidity and mortality after hepatectomy. J Surg Res, 2016; 206:106–112; doi: 10.1016/j.jss.2016.07.013

46.

Gupta

, Fuks

, Bourdeaux

, et al. Impact of intraoperative blood loss on the short-term outcomes of laparoscopic liver resection. Surg Endosc, 2017; 31:4451–4457; doi: 10.1007/s00464-017-5496-y

47.

Cheung

, Poon

, Yuen

, et al. Long-term survival analysis of pure laparoscopic versus open hepatectomy for hepatocellular carcinoma in patients with cirrhosis: A single-center experience. Ann Surg, 2013; 257:506–511; doi: 10.1097/SLA.0b013e31827b947a

48.

Yin

, Fan

, Ye

, et al. Short- and long-term outcomes after laparoscopic and open hepatectomy for hepatocellular carcinoma: A global systematic review and meta-analysis. Ann Surg Oncol, 2013; 20:1203–1215; doi: 10.1245/s10434-012-2705-8

49.

Komorowski

, Mituś JW, Wysocki WM, et al. Laparoscopic and open liver resection - a literature review with meta-analysis. Arch Med Sci, 2017; 13:525–532; doi: 10.5114/aoms.2015.55545

50.

Oba

, Ishizawa

, Mise

, et al. Possible underestimation of blood loss during laparoscopic hepatectomy. BJS Open, 2019; 3:336–343; doi: 10.1002/bjs5.50145

51.

Tomimaru

, Noguchi

, Morita

, et al. Is intraoperative blood loss underestimated in patients undergoing laparoscopic hepatectomy?. World J Surg, 2018; 42:3685–3691; doi: 10.1007/s00268-018-4655-1

52.

Mirnezami

, Mirnezami

, Chandrakumaran

, et al. Short- and long-term outcomes after laparoscopic and open hepatic resection: Systematic review and meta-analysis. HPB (Oxford), 2011;13:295–308; doi: 10.1111/j.1477–2574.2011.00295.x

53.

Terasawa

, Ishizawa

, Mise

, et al. Applications of fusion-fluorescence imaging using indocyanine green in laparoscopic hepatectomy. Surg Endosc, 2017; 31:5111–5118; doi: 10.1007/s00464-017-5576-z

54.

Witowski

, Rubinkiewicz

, Mizera

, et al. Meta-analysis of short- and long-term outcomes after pure laparoscopic versus open liver surgery in hepatocellular carcinoma patients. Surg Endosc, 2019; 33:1491–1507; doi: 10.1007/s00464-018-6431-6

55.

Oishi

, Itamoto

, Kohashi

, et al. Safety of hepatectomy for elderly patients with hepatocellular carcinoma. World J Gastroenterol, 2014; 20:15028–15036; doi: 10.3748/wjg.v20.i41.15028

56.

Wabitsch

, Haber

, Ekwelle

, et al. Minimally invasive liver surgery in elderly patients-a single-center experience. J Surg Res, 2019; 239:92–97; doi: 10.1016/j.jss.2019.01.058

57.

Okholm

, Goetze

, Svendsen

, et al. Inflammatory response in laparoscopic vs. open surgery for gastric cancer. Scand J Gastroenterol, 2014; 49:1027–1034; doi: 10.3109/00365521.2014.917698

58.

Liu

, Min

, Ma

, et al. Laparoscopic hepatectomy produces better outcomes for hepatolithiasis than open hepatectomy: An updated systematic review and meta-analysis. Int J Surg, 2018; 51:151–163; doi: 10.1016/j.ijsu.2018.01.016

59.

Jin

, Chen

, Fei

, et al. Safety and efficacy for laparoscopic versus open hepatectomy: A meta-analysis. Surg Oncol, 2018; 27:A26–A34; doi: 10.1016/j.suronc.2017.06.007

60.

Ciria

, Gomez-Luque

, Ocaña

, et al. A systematic review and meta-analysis comparing the short- and long-term outcomes for laparoscopic and open liver resections for hepatocellular carcinoma: Updated results from the european guidelines meeting on laparoscopic liver surgery, Southampton, UK, 2017. Ann Surg Oncol, 2019; 26:252–263; doi: 10.1245/s10434-018-6926-3

61.

, Zhang

, Wang

, et al. Surgical and oncological outcomes after laparoscopic vs. open major hepatectomy for hepatocellular carcinoma: A systematic review and meta-analysis. Transl Cancer Res, 2020; 9: 3324–3338; doi: 10.21037/tcr.2020.04.01

62.

Chen

, Pan

, Zhang

, et al. Laparoscopic versus open surgery for hepatocellular carcinoma: A meta-analysis of high-quality case-matched studies. Can J Gastroenterol Hepatol, 2018; 2018:1746895; doi: 10.1155/2018/1746895

63.

Xiangfei

, Yinzhe

, Yingwei

, et al. Open versus laparoscopic hepatic resection for hepatocellular carcinoma: A systematic review and meta-analysis. Surg Endosc, 2019; 33:2396–2418; doi: 10.1007/s00464-019-06781-3

64.

, Zhou

, Huang

, et al. Laparoscopic surgery minimizes the release of circulating tumor cells compared to open surgery for hepatocellular carcinoma. Surg Endosc, 2015; 29:3146–3153; doi: 10.1007/s00464-014-4041-5

65.

Ahn

, Teng

, Chen

, et al. Detection of circulating tumor cells and their implications as a biomarker for diagnosis, prognostication, and therapeutic monitoring in hepatocellular carcinoma. Hepatology, 2021; 73:422–436; doi: 10.1002/hep.31165

66.

Cui

, Ou

, Shen

, et al. Clinical value of circulating tumor cells for the diagnosis and prognosis of hepatocellular carcinoma (HCC): A systematic review and meta-analysis. Medicine (Baltimore), 2020; 99:e22242; doi: 10.1097/MD.0000000000022242

67.

Chu

KKW

, Chok

KSH

. Is the treatment outcome of hepatocellular carcinoma inferior in elderly patients?. World J Gastroenterol, 2019; 25:3563–3571; doi: 10.3748/wjg.v25.i27.3563

68.

Hsu

, Yu

, Yang

, et al. Long-term outcomes in elderly patients with resectable large hepatocellular carcinoma undergoing hepatectomy. Surg Oncol, 2018; 27:595–601; doi: 10.1016/j.suronc.2018.07.009

69.

, Yan

, Chen

, et al. The efficacy and safety of totally laparoscopic hepatectomy for non-cirrhotic hepatocellular carcinoma in the elderly. BMC Surg, 2018; 18:118; doi: 10.1186/s12893-018-0444-x

70.

Wang

, Huang

, Guo

, et al. Short- and long-term outcomes of laparoscopic hepatectomy in elderly patients with hepatocellular carcinoma. J BUON, 2018; 23:971–978.

71.

Fagenson

, Gleeson

, Nabi

, et al. When does a Pringle Maneuver cause harm?. HPB (Oxford), 2021; 23:587–594; doi: 10.1016/j.hpb.2020.07.014

72.

Yang

, Liu

, et al. Impact of postoperative infective complications on long-term survival after liver resection for hepatocellular carcinoma. Br J Surg, 2019; 106:1228–1236; doi: 10.1002/bjs.11231

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.05 MB