The Benefits of Radical Treatments with Synchronous Splenectomy for Patients with Hepatocellular Carcinoma and Portal Hypertension
Abstract
:Simple Summary
Abstract
1. Introduction
2. Material and Methods
2.1. Patients
2.2. Preoperative Assessment
2.3. Surgical Procedure and Intraoperative Management
2.4. Postoperative Treatment
2.5. Follow-Up
2.6. Statistical Analysis
3. Results
3.1. Preoperative Characteristics and Intraoperative Data
3.2. Survival Outcomes: RFS and OS
3.3. Prognostic Factors
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Cao, W.; Chen, H.D.; Yu, Y.W.; Li, N.; Chen, W.Q. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin. Med. J. 2021, 134, 783–791. [Google Scholar] [CrossRef] [PubMed]
- De Lorenzo, S.; Tovoli, F.; Barbera, M.A.; Garuti, F.; Palloni, A.; Frega, G.; Garajova, I.; Rizzo, A.; Trevisani, F.; Brandi, G. Metronomic capecitabine vs. best supportive care in Child-Pugh B hepatocellular carcinoma: A proof of concept. Sci. Rep. 2018, 8, 9997. [Google Scholar] [CrossRef] [PubMed]
- Rizzo, A.; Dadduzio, V.; Ricci, A.D.; Massari, F.; Di Federico, A.; Gadaleta-Caldarola, G.; Brandi, G. Lenvatinib plus pembrolizumab: The next frontier for the treatment of hepatocellular carcinoma? Expert Opin. Investig. Drugs 2022, 31, 371–378. [Google Scholar] [CrossRef] [PubMed]
- Rizzo, A.; Ricci, A. PD-L1, TMB, and other potential predictors of response to immunotherapy for hepatocellular carcinoma: How can they assist drug clinical trials? Expert Opin. Investig. Drugs 2022, 31, 415–423. [Google Scholar] [CrossRef] [PubMed]
- National Health Care Commission. Guidelines for the diagnosis and treatment of primary liver cancer (2022 edition). Chin. Arch. Gen. Surg. 2022, 16, 81–96. [Google Scholar]
- Li, W.; Shen, S.Q.; Wu, S.M.; Chen, Z.B.; Hu, C.; Yan, R.C. Simultaneous hepatectomy and splenectomy versus hepatectomy alone for hepatocellular carcinoma complicated by hypersplenism: A meta-analysis. Onco Targets Ther. 2015, 8, 2129–2137. [Google Scholar] [CrossRef] [Green Version]
- Zhang, X.; Li, C.; Wen, T.; Peng, W.; Yan, L.; Li, B.; Yang, J.; Wang, W.; Xu, M.; Zeng, Y. Synchronous splenectomy and hepatectomy for patients with small hepatocellular carcinoma and pathological spleen-neutrophil to lymphocyte ratio changes can predict the prognosis. Oncotarget 2017, 8, 46298–46311. [Google Scholar] [CrossRef]
- Xie, X.L.; Liu, X.; Ou, J. Is synchronous hepatectomy and splenectomy superior to hepatectomy alone for selected patients with hepatocellular carcinoma and clinically significant portal hypertension? J. Surg. Oncol. 2019, 120, 316–317. [Google Scholar] [CrossRef]
- Zhang, X.Y.; Li, C.; Wen, T.F.; Yan, L.N.; Li, B.; Yang, J.Y.; Wang, W.T.; Jiang, L. Synchronous splenectomy and hepatectomy for patients with hepatocellular carcinoma and hypersplenism: A case-control study. World J. Gastroenterol. 2015, 21, 2358–2366. [Google Scholar] [CrossRef]
- European Association for the Study of The Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma. Eur. J. Cancer 2012, 48, 599–641. [Google Scholar] [CrossRef]
- Dietrich, C.F.; Bamber, J.; Berzigotti, A.; Bota, S.; Cantisani, V.; Castera, L.; Cosgrove, D.; Ferraioli, G.; Friedrich-Rust, M.; Gilja, O.H.; et al. EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version). Ultraschall Med. 2017, 38, e16–e47. [Google Scholar] [PubMed] [Green Version]
- Sugawara, Y.; Yamamoto, J.; Shimada, K.; Yamasaki, S.; Kosuge, T.; Takayama, T.; Makuuchi, M. Splenectomy in Patients with Hepatocellular Carcinoma and Hypersplenism. J. Am. Coll. Surg. 2000, 190, 446–450. [Google Scholar] [CrossRef]
- Takayama, T.; Makuuchi, M.; Yamazaki, S.; Hasegawa, H. The role of splenectomy in patients with hepatocellular carcinoma and hypersplenism as an aid to hepatectomy. Nihon Geka Gakkai Zasshi 1989, 90, 1043–1048. [Google Scholar] [PubMed]
- Takeishi, K.; Kawanaka, H.; Itoh, S.; Harimoto, N.; Ikegami, T.; Yoshizumi, T.; Shirabe, K.; Maehara, Y. Impact of Splenic Volume and Splenectomy on Prognosis of Hepatocellular Carcinoma Within Milan Criteria After Curative Hepatectomy. World J. Surg. 2018, 42, 1120–1128. [Google Scholar] [CrossRef]
- Chen, X.P.; Wu, Z.D.; Huang, Z.Y.; Qiu, F.Z. Use of hepatectomy and splenectomy to treat hepatocellular carcinoma with cirrhotic hypersplenism. Br. J. Surg. 2005, 92, 334–339. [Google Scholar] [CrossRef]
- Athanasiou, A.; Spartalis, E.; Hennessy, M.; Spartalis, M.; Moris, D.; Damaskos, C.; Pikoulis, E. Effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats: What we know so far? Hepatobiliary Pancreat. Dis. Int. 2018, 17, 91–92. [Google Scholar] [CrossRef]
- Hirakawa, Y.; Ogata, T.; Sasada, T.; Yamashita, T.; Itoh, K.; Tanaka, H.; Okuda, K. Immunological consequences following splenectomy in patients with liver cirrhosis. Exp. Ther. Med. 2019, 18, 848–856. [Google Scholar] [CrossRef]
- Chai, Z.T.; Zhang, X.P.; Shao, M.; Ao, J.Y.; Chen, Z.H.; Zhang, F.; Hu, Y.R.; Zhong, C.Q.; Lin, J.H.; Fang, K.P.; et al. Impact of splenomegaly and splenectomy on prognosis in hepatocellular carcinoma with portal vein tumor thrombus treated with hepatectomy. Ann. Transl. Med. 2021, 9, 247. [Google Scholar] [CrossRef]
- Jia, Z.; Zhang, K.; Jiang, L.; Huang, R.; He, R.; Wang, Z. Simultaneous radiofrequency ablation combined with laparoscopic splenectomy: A safe and effective way for patients with hepatocellular carcinoma complicated with cirrhosis and hypersplenism. Minim. Invasive Ther. Allied Technol. 2020, 29, 177–184. [Google Scholar] [CrossRef]
- Kong, J.; Shen, S.; Wang, W. Synchronous hepatectomy and splenectomy vs hepatectomy for selected patients with hepatocellular carcinoma and clinically significant portal hypertension: A systematic review and meta-analysis. J. Surg. Oncol. 2019, 119, 964–973. [Google Scholar] [CrossRef]
- Liu, X.; Chen, Z.; Yu, M.; Zhou, W.; Zhi, X.; Li, T. Safety of Simultaneous Hepatectomy and Splenectomy in the Treatment of Hepatocellular Carcinoma Complicated with Hypersplenism: A Meta-analysis. Gastroenterol. Res. Pract. 2019, 2019, 9065845. [Google Scholar] [CrossRef] [PubMed]
- Pei, Y.; Chai, S.; Zhang, Y.; Zhang, Z.; Chen, X.; Zhang, W. Benefits of Splenectomy and Curative Treatments for Patients with Hepatocellular Carcinoma and Portal Hypertension: A Retrospective Study. J. Gastrointest. Surg. 2019, 23, 2151–2162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hu, K.; Lei, P.; Yao, Z.; Wang, C.; Wang, Q.; Xu, S.; Xiong, Z.; Huang, H.; Xu, R.; Deng, M.; et al. Laparoscopic RFA with splenectomy for hepatocellular carcinoma. World J. Surg. Oncol. 2016, 14, 196. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huo, T.I.; Ho, S.Y.; Hsu, C.Y. Microvascular Invasion as a Prognostic Predictor in Hepatocellular Carcinoma: How Accurate Is It? Liver Cancer 2020, 9, 787–788. [Google Scholar] [CrossRef]
- Shindoh, J.; Kobayashi, Y.; Kawamura, Y.; Akuta, N.; Kobayashi, M.; Suzuki, Y.; Ikeda, K.; Hashimoto, M. Microvascular Invasion and a Size Cutoff Value of 2 cm Predict Long-Term Oncological Outcome in Multiple Hepatocellular Carcinoma: Reappraisal of the American Joint Committee on Cancer Staging System and Validation Using the Surveillance, Epidemiology, and End-Results Database. Liver Cancer 2020, 9, 156–166. [Google Scholar]
Variables | HS (n = 96) |
---|---|
Gender, male/female, n (%) | 58 (60)/38 (40) |
Age(year), Mean ± SD | 54 ± 9 |
Etiology, HBV/HCV/alcohol or others, n (%) | 76 (79)/14 (15)/6 (6) |
History of HCC treatment, yes/no, n (%) | 22 (23)/74 (77) |
Preoperative anti-viral therapy, yes/no, n (%) | 56 (58)/40 (42) |
Varices hemorrhage, yes/no, n (%) | 43 (45)/53 (55) |
WBC (×109/L), Median (IQR) | 2.3 (1.8, 3.4) |
HGB (g/L), Median (IQR) | 114.5 (88, 134.2) |
PLT (×109/L), Median (IQR) | 47 (37, 65.2) |
ALT (U/L), Median (IQR) | 28.5 (19, 41) |
Tbil (umol/L), Median (IQR) | 21 (15.3, 28.7) |
Albumin (g/L), Mean ± SD | 36.1 ± 5.4 |
Child-Pugh score, n (%) | |
5 | 33 (34) |
6 | 36 (38) |
7 | 17 (18) |
8 | 8 (8) |
9 | 2 (2) |
AFP (ng/mL), Median (IQR) | 23.7 (3.4, 234.2) |
PTA (%), Mean ± SD | 72.5 ± 12.7 |
Fibroscan (Kpa), Median (IQR) | 20.9 (14.5, 27.2) |
Tumor diameter (mm), Median (IQR) | 24 (14, 39.2) |
Tumor number, 1/2/3, n (%) | 82 (85)/10 (10)/4 (4) |
Tumor stage, 1/2/3, n (%) | 48 (50)/39 (41)/9 (9) |
Vascular invasion, yes/no, n (%) | 37 (39)/59 (61) |
Pathological differentiation, high/middle/low, n (%) | 24 (25)/35 (36)/37 (39) |
MVI, yes/no, n (%) | 23 (24)/73 (76) |
Technique, resection/ablation, n (%) | 56 (58)/40 (42) |
Hassab’s surgery, yes/no, n (%) | 54 (56)/42 (44) |
Blood loss (ml), Median (IQR) | 350 (200, 700) |
Surgical duration (h), Median (IQR) | 4.7 (3.6, 5.8) |
Postoperative hospital stay (d), Median (IQR) | 14.6 (11.1, 19.6) |
Postoperative mortality, n (%) | 5 (5) |
Varices re-hemorrhage during follow-up, n (%) | 25 (26) |
Tumor recurrence during follow-up, n (%) | 62 (65) |
Overall RFS during follow-up (month), Median (IQR) | 22.3 (10.5, 48) |
1-year RFS, n (%) | 67 (70) |
2-year RFS, n (%) | 46 (48) |
3-year RFS, n (%) | 31 (36) |
5-year RFS, n (%) | 18 (22) |
OS(month) during follow-up, Median (IQR) | 46 (22, 68.4) |
1-year OS, n (%) | 86 (90) |
3-year OS, n (%) | 56 (70) |
5-year OS, n (%) | 34 (49) |
Variable | HSS (n = 48) | HA (n = 42) | p-Value |
---|---|---|---|
Gender, n (%) | 0.357 | ||
male | 24 (50) | 26 (62) | |
female | 24 (50) | 16 (38) | |
Age(year), Mean ± SD | 52.6 ± 9.6 | 54 ± 7.9 | 0.438 |
Etiology | 0.054 | ||
HBV | 43 (90) | 30 (71) | |
HCV | 5 (10) | 10 (24) | |
Alcohol or others | 0 (0) | 2 (5) | |
Varices hemorrhage, n (%) | 20 (42) | 2 (5) | <0.001 |
History of HCC treatment, n (%) | 10 (21) | 7 (17) | 0.815 |
Preoperative anti-viral therapy, n (%) | 36 (75) | 31 (74) | 1.000 |
WBC (×109/L), Median (IQR) | 2.2 (1.8, 3.1) | 2.4 (1.9, 2.9) | 0.859 |
HGB (g/L), Median (IQR) | 115 (86.2, 135.2) | 126 (117, 137) | 0.035 |
PLT (×109/L), Median (IQR) | 43 (36.8, 62) | 44.5 (35.2, 56.2) | 0.577 |
ALT (U/L), Median (IQR) | 29 (15.8, 38) | 30.6 (22.4, 45.3) | 0.155 |
Tbil (umol/L), Median (IQR) | 18.4 (14.8, 27.2) | 19.3 (16.4, 25.4) | 0.894 |
Albumin (g/L), Mean ± SD | 36.8 ± 5 | 37.5 ± 3.9 | 0.417 |
Child-Pugh score, n (%) | 0.108 | ||
5 | 20 (42) | 27 (64) | |
6 | 19 (40) | 11 (26) | |
7 | 6 (12) | 4 (10) | |
8 | 3 (6) | 0 (0) | |
AFP (ng/mL), Median (IQR) | 9.9 (2.6, 135.7) | 49.5 (7.8, 204) | 0.05 |
PTA (%), Median (IQR) | 72.5 (67.8, 80.2) | 77.5 (72, 85) | 0.006 |
Fibroscan (Kpa), Median (IQR) | 18.8 (13.9, 25.4) | 14.5 (11.6, 21.7) | 0.018 |
Tumor diameter (mm), Median (IQR) | 19.5 (13.8, 30) | 20 (15, 25) | 0.884 |
Technique, n (%) | 0.327 | ||
resection | 30 (62) | 21 (50) | |
ablation | 18 (38) | 21 (50) | |
Extent of resection, n (%) | 0.341 | ||
local | 16 (53) | 14 (67) | |
anatomical | 14 (47) | 7 (33) | |
Surgical margin (cm), Median (IQR) | 0.5 (0.3, 1) | 0.4 (0.2, 0.9) | 0.753 |
Pathological differentiation | 0.075 | ||
high | 18 (38) | 7 (17) | |
middle | 15 (31) | 20 (48) | |
low | 15 (31) | 15 (36) | |
MVI, n (%) | 0.777 | ||
no | 39 (81) | 36 (86) | |
yes | 9 (19) | 6 (14) | |
Hassab’s surgery, n (%) | 28 (58) | 0 (0) | |
Blood loss (ml), Median (IQR) | 300 (150, 425) | 150 (100, 200) | 0.002 |
Surgical duration (h), Median (IQR) | 4.1 (3.2, 5.5) | 3.5 (2.7, 4.3) | 0.005 |
Postoperative hospital stay (d), Median (IQR) | 15 (11.5, 17.6) | 13.6 (9.7, 16.9) | 0.127 |
Varices re-hemorrhage during follow-up, n (%) | 12 (25) | 4 (10) | 0.101 |
PVT during follow-up, n (%) | 12 (25) | 3 (7) | 0.055 |
Lethal PVT during follow-up, n (%) | 5 (10) | 1 (2) | 0.212 |
Variables | 2-Year RFS | 5-Year OS | ||||
---|---|---|---|---|---|---|
HR | 95% C. I | p-Value | HR | 95% C. I | p-Value | |
Anti-viral therapy (yes vs. no) | 0.553 | 0.329–0.930 | 0.026 | 0.473 | 0.275–0.812 | 0.007 |
Child-Pugh grade (B vs. A) | 2.930 | 1.635–5.252 | 0.000 | |||
Vascular invasion (yes vs. no) | 2.561 | 1.467–4.471 | 0.001 | 2.307 | 1.320–4.031 | 0.003 |
MVI (yes vs. no) | 2.276 | 1.271–4.075 | 0.006 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zhang, Q.; Li, Q.; Shang, F.; Li, G.; Wang, M. The Benefits of Radical Treatments with Synchronous Splenectomy for Patients with Hepatocellular Carcinoma and Portal Hypertension. Cancers 2022, 14, 3155. https://doi.org/10.3390/cancers14133155
Zhang Q, Li Q, Shang F, Li G, Wang M. The Benefits of Radical Treatments with Synchronous Splenectomy for Patients with Hepatocellular Carcinoma and Portal Hypertension. Cancers. 2022; 14(13):3155. https://doi.org/10.3390/cancers14133155
Chicago/Turabian StyleZhang, Qikun, Qi Li, Fuchao Shang, Guangming Li, and Menglong Wang. 2022. "The Benefits of Radical Treatments with Synchronous Splenectomy for Patients with Hepatocellular Carcinoma and Portal Hypertension" Cancers 14, no. 13: 3155. https://doi.org/10.3390/cancers14133155