Abstract
Background
The risk of HCC is documented to be age-related. The outcomes of young HCC patients on postoperative prognosis are not well understood. The study aims to compare the characteristic differences between adolescent and young (AYA) and non-AYA HCC patients.
Methods
We performed a retrospective analysis of the clinical and pathological findings and the survival of 243 HCC patients who underwent operations between 2007 and 2018.
Results
The AYA group had a higher AFP level and a higher prevalence of family history of HCC or other cancers than the non-AYA group (P < 0.01 and P < 0.05). AYA patients had more unfavorable pathological characteristics including bigger lesion size, microvascular invasion, portal vein invasion, and hepatic capsule invasion. They also had a more unfavorable Edmondson grade and less tumor capsule formation (P < 0.01). Age was an independent predictor of survival in HCC patients. AYA patients had poorer disease-free and overall survival than non-AYA patients did (P < 0.01). Patients under 30 years old had an even poorer disease-free survival than those aged 30–40 (P = 0.047).
Conclusions
AYA patients exhibited a higher recurrence rate and disease-related death rate with more unfavorable pathological characteristics. Enhanced follow-up for young HCC patients should be applied.
Keywords: Adolescent and young patient, Characteristic, Outcome, Hepatocellular carcinoma
Introduction
Hepatocellular carcinoma (HCC) is a worldwide disease [1, 2]. The risk of HCC is documented to be age-related [3, 4]. The adolescent and young adult (AYA), defined as individuals under 40 years old in accordance with the National Comprehensive Cancer Network, is a specific population that has different outcomes as compared to others shown by the AYA Oncology Progress Review Group [5]. Previous studies identified that age difference was associated with the prognosis for such cancers as gastric cancer, breast cancer, and colorectal cancer [6–10]. Few studies have focused on the characteristics and outcomes of AYA HCC patients on postoperative prognosis [11]. This study was designed to compare the outcomes between AYA and non-AYA HCC patients.
Methods
Patients
The findings on 243 consecutive patients undergoing curative liver resection for HCC from January 2007 to December 2018 at Shanghai Jiao Tong University Affiliated Sixth People’s Hospital and Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology were retrospectively reviewed. The population of this study consisted of 73 patients whose age was under 40 (AYA) and 170 patients whose age was over 40 (non-AYA). The following are the exclusion criteria: (1) age < 20, (2) recurrent HCC, (3) R1 and R2 resection, (4) postoperative death within 30 days, (6) HCC with preoperative treatment, and (7) missing data on important prognostic factors. This study was approved by the ethics committee of Shanghai Jiao Tong University and was conducted in line with the principles of the Declaration of Helsinki. Each patient had a written informed consent.
Data collection
Patients’ age, sex, HBV infection status, Child-Pugh grading, alanine aminotransferase (ALT), aspartate transaminase (AST), alpha-fetoprotein (AFP), tumor size, tumor number, portal vein invasion, microvascular invasion, satellite nodules, tumor differentiation, tumor encapsulation, family cancer history, and HCC staging [12] were recorded.
Follow-up
Patients were followed up at a 3-month frequency that was composed of a physical examination and a laboratory test. CT scan was arranged once in 3 months for the first year and then once in 6 months for the second year. The primary end-point was recurrence and death. The primary criterion was the survival time.
Statistical analysis
Continuous variables were expressed as median and range or mean ± standard deviation. Categorical variables were expressed as number and percentage. The chi-squared test was used for normal data. Univariate analysis was performed using the χ2 test or Fisher’s exact test for categorical variables. When the data did not normally distribute, the non-parametric Mann-Whitney U test was used. The survival was analyzed by the Kaplan-Meier method with the log-rank test. Significant factors in univariate analysis were subjected to multivariate analysis by Cox proportional hazard regression. Data were considered significant for P < 0.05. The SPSS 20 statistical software (SPSS, Chicago, IL) was used for analyses.
Results
Comparison of the baseline characteristics and pathological outcomes
The AYA group had a higher AFP level and a higher prevalence of family history of HCC or other cancers than the non-AYA group (P < 0.01 and P < 0.05) (Table 1). No differences were found between the two groups for other laboratory examinations. A much higher proportion of AYA patients had a big tumor size (> 5 cm) (P < 0.05), microvascular invasion (P < 0.01), portal vein invasion (P < 0.01), and hepatic capsule invasion (P < 0.01) than that of non-AYA counterparts. The AYA group had a more unfavorable Edmondson grade than the non-AYA group (P < 0.01). However, fewer patients in the AYA group had tumor capsule formation (P < 0.01) (Table 1).
Table 1.
Comparison of the baseline characteristics and pathological outcomes between the AYA and non-AYA groups
| Characteristics | AYA group (n = 73) | Non-AYA group (n = 170) | P value |
|---|---|---|---|
| Age (years) | 36.0 ± 4.4 | 62.0 ± 6.4 | < 0.01 |
| Sex, n (%) | |||
| Male | 56 (76.7%) | 140 (82.4%) | |
| Female | 17 (23.3%) | 30 (17.6) | NS |
| Etiology, n (%) | |||
| HBV | 60 (82.1%) | 141 (83.0%) | |
| Others | 13 (17.8%) | 29 (17.0%) | NS |
| BMI (kg/m2) | 22.1 ± 1.2 | 20.6 ± 0.9 | NS |
| AST (U/L) | 42 (23–119) | 50 (16–269) | NS |
| ALT (U/L) | 62 (22–167) | 54 (9–204) | NS |
| Albumin (g/dL) | 4.2 ± 0.4 | 4.0 ± 0.5 | NS |
| Total bilirubin (mg/dL) | 0.7 ± 0.4 | 0.7 ± 0.4 | NS |
| Platelet (× 103/mm3) | 199 (40–362) | 183 (66–393) | NS |
| INR | 1.1 ± 0.1 | 1.1 ± 0.1 | NS |
| AFP (ng/dL) | 5923 (2–59,403) | 3341 (1–59,779) | < 0.01 |
| PIVKA-II | 271 (10–500) | 238 (11–500) | NS |
| ICG R15 (%) | 8.5 (2.4–41.5) | 10.0 (3.7–48.6) | NS |
| Child-Pugh grade B, n (%) | 2 (3.0%) | 5 (2.9%) | NS |
| Family history of HCC or other cancers, n (%) | 15 (20.5%) | 20 (11.8%) | < 0.05 |
| Maximum tumor size > 5 cm | 42 (57.5%) | 76 (44.1) | < 0.05 |
| Multiple tumors | 6 (8.2%) | 15 (8.8%) | NS |
| Microvascular invasion | 64 (87.7%) | 121 (71.2%) | < 0.01 |
| Portal vein invasion | 24 (32.9%) | 33 (19.4%) | < 0.01 |
| Satellite nodules | 12 (16.4%) | 31 (18.2%) | NS |
| Edmondson grade | |||
| I + II | 36 (49.3%) | 151 (88.8%) | |
| III + IV | 37 (50.7%) | 19 (11.2%) | < 0.01 |
| Tumor capsule formation | 39 (53.4%) | 126 (74.1%) | < 0.01 |
| Hepatic capsule invasion | 8 (11.0%) | 9 (5.3%) | <0.01 |
| Microvascular tumor emboli | 47 (64.4%) | 119 (70.0%) | NS |
| TNM stage | |||
| I + II | 25 (34.2%) | 68 (40.4%) | |
| III + IV | 48 (65.8%) | 102 (60.0%) | NS |
| Resection margin < 1 cm | 36 (49.3%) | 77 (45.3%) | NS |
HCC hepatocellular carcinoma, NS not significant
Survival analysis
In univariate analysis, age, AFP, maximum tumor size, portal vein invasion, satellite nodules, tumor capsule formation, and TNM stage were strongly associated with disease-free and overall survival in HCC patients. In multivariate analysis, age, maximum tumor size, portal vein invasion, satellite nodules, tumor capsule formation, and TNM stage were strongly associated with disease-free survival while age, AFP, maximum tumor size, portal vein invasion, tumor capsule formation, and TNM stage were strongly associated with overall survival in HCC patients (Table 2). AYA patients had poorer disease-free and overall survival than non-AYA patients did (P < 0.01) (Fig. 1A, B and Table 3). In multivariate analysis, maximum tumor size, portal vein invasion, tumor capsule formation, and TNM stage were strongly associated with disease-free survival in both the AYA and non-AYA groups. Maximum tumor size, portal vein invasion, TNM stage, and AFP were strongly associated with overall survival in both groups. Additionally, tumor capsule formation was strongly related to the overall survival in the non-AYA group (Table 4). We further stratified the AYA patients with the cutoff age of 30 years old and performed the survival analysis. As a result, patients under thirty had an even poorer disease-free survival than patients aged 30–40 (P = 0.047). But no significance was found in overall survival (P > 0.05) (Fig. 1C, D).
Table 2.
Univariate and multivariate analysis for disease-free survival and overall survival in HCC patients
| Characteristics | Univariate analysis | Multivariate analysis | ||||||
|---|---|---|---|---|---|---|---|---|
| Disease-free survival | Overall survival | Disease-free survival | Overall survival | |||||
| HR | 95% CI P value |
HR | 95% CI P value |
HR | 95% CI P value |
HR | 95% CI P value |
|
| Age ≤ 40 | 2.2 |
1.2–2.8 < 0.01 |
2.1 | 1.4–2.6 < 0.01 | 1.8 | 1.1–3.1 < 0.01 | 2.3 | 1.3–3.2 < 0.01 |
| AFP ≥ 100 ng/dL | 1.2 |
1.1–2.1 < 0.05 |
1.6 |
1.2–2.4 < 0.05 |
1.9 |
1.2–3.1 < 0.05 |
||
| Sex male | 0.3 | NS | 0.4 | NS | ||||
| HBV-positive | 0.5 | NS | 0.6 | NS | ||||
| BMI ≥ 23 | 0.4 | NS | 0.3 | NS | ||||
| Family history cancers | 0.8 | NS | 0.7 | NS | ||||
| Maximum tumor size > 5 cm | 1.8 |
1.2–3.1 < 0.01 |
1.6 |
1.2–3.4 < 0.01 |
2.1 |
12–4.1 < 0.01 |
1.8 |
1.3–3.5 < 0.01 |
| Multiple tumors | 0.6 | NS | 0.4 | NS | ||||
| Microvascular invasion | 0.6 | NS | 0.8 | NS | ||||
| Portal vein invasion | 2.5 |
1.2–4.3 < 0.01 |
2.0 |
1.3–3.9 < 0.01 |
3.1 |
1.9–4.2 P < 0.01 |
2.2 |
1.3–3.4 P < 0.01 |
| Satellite nodules | 1.8 |
1.1–2.7 < 0.05 |
1.2 |
1.1–2.9 < 0.05 |
1.4 |
1.2–2.9 < 0.05 |
||
| Edmondson grade | 0.5 | NS | 0.3 | NS | ||||
| Tumor capsule formation | 0.4 |
0.1–08 < 0.05 |
0.6 |
0.2–0.9 < 0.05 |
0.5 |
0.1–0.8 < 0.05 |
0.7 |
0.1–0.9 < 0.05 |
| Hepatic capsule invasion | 0.3 | NS | 0.1 | NS | ||||
| Microvascular tumor emboli | 0.4 | NS | 0.2 | NS | ||||
| TNM stage | 3.1 |
1.8–4.9 < 0.01 |
2.2 |
1.5–3.6 < 0.01 |
3.0 |
1.3–4.3 < 0.01 |
2.1 |
1.5–3.9 < 0.01 |
| Resection margin < 1 cm | 0.7 | NS | 0.4 | NS | ||||
NS not significant
Fig. 1.
Disease-free survival and overall survival of patients. A, B AYA patients had poorer disease-free and overall survival than non-AYA patients did (P < 0.01). C, D Patients under thirty had an even poorer disease-free survival than patients aged 30–40 (P = 0.047). However, no significance was found in overall survival (P > 0.05)
Table 3.
One- and 3-year disease-free and overall survival in the AYA and non-AYA groups
| Group | Disease-free survival (%) | Overall survival (%) | ||||||
|---|---|---|---|---|---|---|---|---|
| Median survival time (months) | 1 year | 3 years | P value | Median survival time (months) | 1 year | 3 years | P value | |
| AYA | 9.3 | 34.0 | 18.0 | 14.4 | 51.0 | 18.0 | ||
| Non-AYA | 23.3 | 61.0 | 46.0 | < 0.01 | 59 | 89.0 | 73.0 | < 0.01 |
Table 4.
Multivariate analysis for disease-free survival and overall survival in the AYA and non-AYA groups
| Disease-free survival | Overall survival | |||||
|---|---|---|---|---|---|---|
| HR | 95% CI | P value | HR | 95% CI | P value | |
| AYA group | ||||||
| Maximum tumor size > 5 cm | 1.3 | 1.1–2.4 | < 0.01 | 1.5 | 1.1–2.7 | < 0.01 |
| Portal vein invasion | 1.8 | 1.5–2.3 | < 0.01 | 1.6 | 1.4–2.4 | < 0.01 |
| Tumor capsule formation | 0.6 | 0.3–0.8 | < 0.05 | |||
| TNM stage | 2.1 | 1.5–3.1 | < 0.01 | 3.1 | 2.1–5.4 | < 0.01 |
| AFP > 100 ng/dL | 1.4 | 1.1–2.5 | < 0.01 | |||
| Non-AYA groups | ||||||
| Maximum tumor size > 5 cm | 1.5 | 1.2–2.1 | < 0.01 | 1.7 | 1.2–2.6 | < 0.01 |
| Portal vein invasion | 2.1 | 1.3–3.3 | < 0.01 | 2.5 | 1.4–3.5 | < 0.01 |
| Satellite nodules | 1.9 | 1.3–2.7 | < 0.05 | |||
| Tumor capsule formation | 0.5 | 0.2–0.9 | < 0.05 | 0.7 | 0.3–0.9 | < 0.01 |
| TNM stage | 2.7 | 1.3–4.1 | < 0.01 | 1.8 | 1.1–3.1 | < 0.01 |
| AFP > 100 ng/dL | 2.0 | 1.2–4.1 | < 0.05 | |||
Comparison of the pathological outcomes within AYA patients
To identify the cause of even shorter disease-free survival in AYA patients under 30 years old, we conducted a comparison analysis. We found that patients under 30 years old had more unfavorable pathological manifestations including satellite nodules, hepatic capsule invasion, and poor Edmondson grade (P < 0.01) (Table 5).
Table 5.
Pathological outcomes of HCC patients under 40 years old
| Variable, n (%) | Age < 30 (n = 10) | 30 < age < 40 (n = 63) | P value |
|---|---|---|---|
| Satellite nodules | 3 (30.0%) | 9 (14.3%) | < 0.01 |
| Edmondson grade | |||
| I + II | 3 (30.0%) | 33 (52.4%) | |
| III + IV | 7 (70.0%) | 30 (47.6%) | < 0.01 |
| Hepatic capsule invasion | 2 (20.0%) | 6 (9.5%) | < 0.01 |
Discussion
Among solid tumors in the elderly, the age-related incidence of HCC is found in the population older than 70 years old [13]. HCC is also commonly seen in young patients in places that are endemic to hepatitis B virus such as East Asia [14, 15]. Hepatectomy remains the most effective treatment for HCC despite the unsatisfactory outcomes of HCC associated with portal vein tumor thrombosis [16]. Identification of prognostic risk factors is critical to improve the survival. Considering the small number of AYA HCC samples in many institutions, few studies had focused on the outcomes for the younger patients in particular. This study was designed to identify the factors affecting the survival of AYA HCC patients with a relatively larger case number.
Compared to other patients, AYA represents a unique oncological population in many ways [17]. In some publications, AYA patients were shown to have a poor prognosis because of the advanced stage [18]. However, in other studies, AYA patients shared similar disease-free or overall survival with the older patients, and age itself was an independent factor for prognosis [19, 20]. However, the case numbers enrolled in those studies were small which might lead to statistical bias. In these studies, most AYA patients have a history of hepatitis B with a good liver function that could delay the diagnosis of HCC. Similarly, we found in this study that 82.2% of AYA patients had a positive HBV infection, and 97.0% had a liver function of Child-Pugh A. More importantly, we found that age was an independent predictor of survival in HCC patients. AYA patients had poorer disease-free and overall survival than non-AYA patients did. AYA patients had a higher preoperative AFP level and more unfavorable pathological characteristics including tumor size, microvascular invasion, portal vein invasion, and hepatic capsule invasion. They also had a more unfavorable Edmondson grade and less tumor capsule formation than non-AYA patients did. In addition, we found that AYA patients a higher prevalence of family history of HCC or other cancers than non-AYA patients. It is reasonable to estimate that young HCC patients are likely to have genetic factors contributing to the onset of cancers. A recent study implied that apoptosis-related genes in HCC were associated with the patient’s prognosis [21]. Furthermore, tumor size, vascular invasion, tumor capsule formation, satellite nodules, TNM stage, and AFP were identified as the significant variables both for disease-free and overall survival, which were in line with the previous studies [22–25]. Zhao et al. found that BMI did not affect the patient’s long-term surgical outcomes concerned to overall and disease-free survival [26], and in line with which, we did not find the difference in BMI between these two groups and its impact on patient’s survival. In agreement with Saito et al. [25], we found that the larger tumor size was associated with unfavorable outcomes. In addition, another study reported that the very early recurrence nomogram contained microvascular invasion, macrovascular invasion, and CA199 level [27]. In this study, we further stratified the AYA patients with the cutoff age of 30 years old and performed the survival analysis again. Interestingly, we found that patients under thirty had an even poorer disease-free survival than patients aged 30–40. To investigate the cause of this finding, we conducted a comparison analysis. We found that patients under thirty had more unfavorable pathological manifestations including satellite nodules, hepatic capsule invasion, and poor Edmondson grade. This study had some limitations concerning its retrospective nature. Though there were limitations in this study, the differences between the groups were remarkable.
Conclusions
In conclusion, AYA patients exhibited a higher risk of recurrence and disease-related death with more unfavorable pathological characteristics. Enhanced follow-up for those chronic hepatitis B AYA carriers should be applied. Adjuvant sorafenib therapy after resection in HCC patients is suggested since it prolongs the overall and disease-free survival and reduces the recurrence rate without intolerable side effects [28].
Acknowledgements
Not applicable
Abbreviations
- AYA
Adolescent and young adult
- HCC
Hepatocellular carcinoma
- ALT
Alanine aminotransferase
- AST
Aspartate transaminase
- AFP
Alpha-fetoprotein
Authors’ contributions
Conception and design: Di-Si Hao and Zun-Qiang Zhou. Administrative support: Zheng-Yun Zhang, Jiao Guan, Xin-Ping Wang, and Di-Si Hao. Provision of study materials or patients: Zheng-Yun Zhang, Jiao Guan, Xin-Ping Wang, and Di-Si Hao. Collection and assembly of data: all authors. Data analysis and interpretation: Zheng-Yun Zhang, Jiao Guan, and Xin-Ping Wang. Manuscript writing: all authors. Final approval of the manuscript: all authors.
Funding
This study was supported by grants from the National Natural Science Foundation of China (81974379), the Natural Science Foundation of Shanghai (19ZR1438700), and the Interdisciplinary Program of Shanghai Jiao Tong University (ZH2018QNB05).
Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding authors on reasonable request.
Declarations
Ethics approval and consent to participate
This study was approved by the ethics committee of Shanghai Jiao Tong University and was conducted according to the principles outlined in the Declaration of Helsinki. Each patient provided a written informed consent.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Zheng-Yun Zhang and Jiao Guan contributed equally to this work.
Contributor Information
Di-Si Hao, Email: dshao1968@sina.com.
Zun-Qiang Zhou, Email: surgeon_zhou@163.com.
References
- 1.Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi: 10.3322/caac.20107. [DOI] [PubMed] [Google Scholar]
- 2.Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004;127:S5–16. doi: 10.1053/j.gastro.2004.09.011. [DOI] [PubMed] [Google Scholar]
- 3.Cho SJ, Yoon JH, Hwang SS, Lee HS. Do young hepatocellular carcinoma patients with relatively good liver function have poorer outcomes than elderly patients? J Gastroenterol Hepatol. 2007;22:1226–1231. doi: 10.1111/j.1440-1746.2007.04914.x. [DOI] [PubMed] [Google Scholar]
- 4.Asahina Y, Tsuchiya K, Tamaki N, Hirayama I, Tanaka T, Sato M, et al. Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis c virus infection. Hepatology. 2010;52:518–527. doi: 10.1002/hep.23691. [DOI] [PubMed] [Google Scholar]
- 5.Bleyer A. Adolescent and Young Adult (AYA) Oncology in the United States: a specialty in its late adolescence. J Pediatr Hematol Oncol. 2015;37:161–169. doi: 10.1097/MPH.0000000000000318. [DOI] [PubMed] [Google Scholar]
- 6.Kath R, Fiehler J, Schneider CP, Höffken K. Gastric cancer in very young adults: apropos four patients and a review of the literature. J Cancer Res Clin Oncol. 2000;126:233–237. doi: 10.1007/s004320050038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Wang J, Wang J, Li Q, Zhang P, Yuan P, Ma F, et al. Young breast cancer patients who develop distant metastasis after surgery have better survival outcomes compared with elderly counterparts. Oncotarget. 2017;8:44851–44859. doi: 10.18632/oncotarget.15268. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Fu J, Yang J, Tan Y, Jiang M, Wen F, Huang Y, et al. Young patients (≤ 35 years old) with colorectal cancer have worse outcomes due to more advanced disease: a 30-year retrospective review. Medicine (Baltimore) 2014;93:e135. doi: 10.1097/MD.0000000000000135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Cheng L, Chen S, Wu W, Kuo ZC, Wei Z, Meng S, et al. Gastric cancer in young patients: a separate entity with aggressive features and poor prognosis. J Cancer Res Clin Oncol. 2020;146:2937–2947. doi: 10.1007/s00432-020-03268-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Theuer CP, Kurosaki T, Taylor TH, Anton-Culver H. Unique features of gastric carcinoma in the young: a population-based analysis. Cancer. 1998;83:25–33. doi: 10.1002/(SICI)1097-0142(19980701)83:1<25::AID-CNCR4>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
- 11.Zhang W, Tan Y, Shen S, Jiang L, Yan L, Yang L, et al. Prognostic nomogram for hepatocellular carcinoma in adolescent and young adult patients after hepatectomy. Oncotarget. 2017;8:106393–106404. doi: 10.18632/oncotarget.18192. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Chun YS, Pawlik TM, Vauthey JN. 8th edition of the AJCC cancer staging manual: pancreas and hepatobiliary cancers. Ann Surg Oncol. 2018;25:845–847. doi: 10.1245/s10434-017-6025-x. [DOI] [PubMed] [Google Scholar]
- 13.El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–2576. doi: 10.1053/j.gastro.2007.04.061. [DOI] [PubMed] [Google Scholar]
- 14.Lam CM, Chan AO, Ho P, Ng IO, Lo CM, Liu CL, et al. Different presentation of hepatitis B-related hepatocellular carcinoma in a cohort of 1863 young and old patients – implications for screening. Aliment Pharmacol Ther. 2004;19:771–777. doi: 10.1111/j.1365-2036.2004.01912.x. [DOI] [PubMed] [Google Scholar]
- 15.Ishikawa T. Clinical features of hepatitis B virus-related hepatocellular carcinoma. World J Gastroenterol. 2010;16:2463–2467. doi: 10.3748/wjg.v16.i20.2463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Wang YC, Lee JC, Wu TH, Cheng CH, Lee CF, Wu TJ, et al. Improving outcomes of liver resection for hepatocellular carcinoma associated with portal vein tumor thrombosis over the evolving eras of treatment. World J Surg Oncol. 2021;19:313. doi: 10.1186/s12957-021-02425-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Richter D, Koehler M, Friedrich M, Hilgendorf I, Mehnert A, Weißflog G. Psychosocial interventions for adolescents and young adult cancer patients: a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2015;95:370–386. doi: 10.1016/j.critrevonc.2015.04.003. [DOI] [PubMed] [Google Scholar]
- 18.Yamazaki Y, Kakizaki S, Sohara N, Sato K, Takagi H, Arai H, et al. Hepatocellular carcinoma in young adults: the clinical characteristics, prognosis, and findings of a patient survival analysis. Dig Dis Sci. 2007;52:1103–1107. doi: 10.1007/s10620-006-9578-2. [DOI] [PubMed] [Google Scholar]
- 19.Liu XY, Xu JF. Liver resection for young patients with large hepatocellular carcinoma: a single center experience from China. World J Surg Oncol. 2014;12:175. doi: 10.1186/1477-7819-12-175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Lee CR, Lim JH, Kim SH, Ahn SH, Park YN, Choi GH, et al. A comparative analysis of hepatocellular carcinoma after hepatic resection in young versus elderly patients. J Gastrointest Surg. 2012;16:1736–1743. doi: 10.1007/s11605-012-1966-7. [DOI] [PubMed] [Google Scholar]
- 21.Liu R, Wang G, Zhang C, Bai D. A prognostic model for hepatocellular carcinoma based on apoptosis-related genes. World J Surg Oncol. 2021;19:70. doi: 10.1186/s12957-021-02175-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Lim KC, Chow PK, Allen JC, Chia GS, Lim M, Cheow PC, et al. Microvascular invasion is a better predictor of tumor recurrence and overall survival following surgical resection for hepatocellular carcinoma compared to the Milan criteria. Ann Surg. 2011;254:108–113. doi: 10.1097/SLA.0b013e31821ad884. [DOI] [PubMed] [Google Scholar]
- 23.Zhou L, Rui JA, Wang SB, Chen SG, Qu Q. Prognostic factors of solitary large hepatocellular carcinoma: the importance of differentiation grade. Eur J Surg Oncol. 2011;37:521–525. doi: 10.1016/j.ejso.2011.03.137. [DOI] [PubMed] [Google Scholar]
- 24.Bruix J, Sherman M. American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–1022. doi: 10.1002/hep.24199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Saito R, Amemiya H, Hosomura N, Kawaida H, Shoda K, Furuya S, et al. Intended preoperative trans-arterial embolization for large hepatocellular carcinoma: a retrospective cohort study. World J Surg Oncol. 2022;20:90. doi: 10.1186/s12957-022-02563-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Zhao L, Wang J, Kong J, Zheng X, Yu X. The impact of body mass index on short-term and long-term surgical outcomes of laparoscopic hepatectomy in liver carcinoma patients: a retrospective study. World J Surg Oncol. 2022;20:150. doi: 10.1186/s12957-022-02614-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Wu Y, Liu H, Zeng J, Chen Y, Fang G, Zhang J, et al. Development and validation of nomogram to predict very early recurrence of combined hepatocellular-cholangiocarcinoma after hepatic resection: a multi-institutional study. World J Surg Oncol. 2022;20:60. doi: 10.1186/s12957-022-02536-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Huang S, Li D, Zhuang L, Sun L, Wu J. A meta-analysis of the efficacy and safety of adjuvant sorafenib for hepatocellular carcinoma after resection. World J Surg Oncol. 2021;19:168. doi: 10.1186/s12957-021-02280-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and analyzed during the current study are available from the corresponding authors on reasonable request.