Laparoscopic RFA with splenectomy for hepatocellular carcinoma
- Kunpeng Hu†1,
- Purun Lei†2,
- Zhicheng Yao†1,
- Chenhu Wang3,
- Qingliang Wang1,
- Shilei Xu1,
- Zhiyong Xiong4,
- He Huang1,
- Ruiyun Xu4,
- Meihai Deng4 and
- Bo Liu1Email author
© The Author(s). 2016
Received: 14 January 2016
Accepted: 20 July 2016
Published: 27 July 2016
The treatment of hepatocellular carcinoma (HCC) is complicated and challenging because of the frequent presence of cirrhosis. Therefore, we propose a novel surgical approach to minimize the invasiveness and risk in patients with HCC, hypersplenism, and esophagogastric varices.
This was a retrospective study carried out in 25 patients with HCC and hypersplenism and who underwent simultaneous laparoscopic-guided radio-frequency ablation and laparoscopic splenectomy with endoscopic variceal ligation. Tumor size was restricted to a single nodule of <3 cm. Characteristics of the patients (cirrhosis etiology, liver function, tumor size, spleen size), surgery (complications, blood loss, time of stay), and follow-up (recurrence and survival) were examined.
Mean operative time was 128 ± 18 min. Mean blood loss was 206 ± 57 mL. Length of stay was 7.0 ± 1.5 days. Mean total costs were 8064 USD. Cytopenia and thrombocytopenia recovered quickly after surgery. No procedure was converted to open surgery. Two patients showed worsening liver function after surgery, three patients showed worsening of ascites, and five patients suffered from portal vein thrombosis. The 1-year tumor-free survival was 78.8 %, and the 21-month tumor-free survival was 61.4 %. According to a literature review, these outcomes were comparable to those of simultaneous open hepatic resection and splenectomy.
Laparoscopic-guided radio-frequency ablation with laparoscopic splenectomy and endoscopic variceal ligation could be an available technique for patients with HCC <3 cm, hypersplenism, and esophagogastric varices. This approach may help to minimize the surgical risks and results in a fast increase in platelet counts with an acceptable rate of complications.
Hepatocellular carcinoma (HCC) is one of most common cancers in China . The treatment of HCC is complicated and challenging due to the frequent presence of hepatic cirrhosis and portal hypertension, which may result in coagulation dysfunction, esophagogastric varices, anemia, abdominal collaterals, and peripheral cytopenia, particularly thrombocytopenia [2–5].
Therefore, treatment for HCC should remove the tumor with minimal invasiveness. Cirrhotic hypersplenism can result in peripheral cytopenia. Because cytopenia is reversible after splenectomy, splenic embolism or resection seems to be an appropriate choice. Simultaneous hepatectomy and splenectomy are associated with improved 5-year tumor-free survival in patients with HCC and hypersplenism , and laparoscopic splenectomy (Lap-sp) has recently become a potential choice . Moreover, radio-frequency ablation (RFA) has been reported to have the same outcomes as liver resection for patients with tumors <3 cm [8–10].
In an animal model, splenectomy improved the status of hepatic cirrhosis  and helped hepatic recovery, promoting liver regeneration after massive liver resection . Recently, some studies reported that liver function was improved after splenectomy in patients with portal hypertension and hypersplenism.
Therefore, the objective of this study was to investigate the effects of laparoscopic-guided RFA with Lap-sp and endoscopic variceal ligation in patients with HCC <3 cm, cirrhosis, and esophagogastric varices.
This was a retrospective study carried out in 25 patients with HCC, hypersplenism, and esophagogastric varices and who underwent simultaneous laparoscopic-guided ablation and Lap-sp with endoscopic variceal ligation between January 2012 and October 2014 at the Department of General Surgery at the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). Informed contents were accepted and signed off by all patients and their family members before surgery. The study was approved by the Committee of Ethics of the Third Affiliated Hospital of Sun Yat-sen University. Written informed consent was obtained from the patient for the publication of this report and any accompanying images.
At our center, selection criteria for this surgical approach were (1) 18–70 years old; (2) diagnosis of HBV- or HCV-related liver cirrhosis with portal hypertension; (3) spleen thickness >4.1 cm; (4) HCC ≤3 cm; (5) first surgical attempt; (6) severe esophagogastric varicosity confirmed by gastroscopy; (7) Child-Pugh class A or B, score ≤9; and (8) platelets ≤50 × 109/L and leukocytes ≤3.5 × 109/L. This approach was not proposed to patients in case of (1) other tumors; (2) HIV-positive test; (3) any immunodeficiency or autoimmune disease (e.g., rheumatic arthritis, Buerger’s disease, multiple sclerosis, type 1 diabetes); (4) any organ failure; or (5) mental illness.
Surgery was performed under general anesthesia with the patient in the right semi-decubitus position. Five trocars with a diameter of 5 mm/12 mm were introduced into the abdominal cavity through the left upper quadrant of the abdomen. The abdominal cavity was insufflated with 13–15 mmHg of CO2, and a 30° laparoscope was inserted. Mobilization of the spleen was performed using the Ligasure vessel sealing system and an ultrasonic scalpel. The tissues around the splenic hilum including the splenic arteries and veins were cut using an autosuture device, and the spleen was freed. The spleen was packed in a plastic sac and cut into pieces using scissors through one of the trocar ports. The fragmented spleen was then removed with the sac from the abdomen without extending the wound. Next, the RFA needle was inserted into the center of the target HCC nodule by the radiologist. RFA was applied continuously for 8–12 min. The endpoint of RFA was determined mainly according to ultrasonography of an index tumor that was fully covered by the hyperechoic ablated zone. Finally, endoscopic ligation was performed as classically described . All patients were treated by the same surgical team. An empirical course of antibiotics was started 30 min before surgery and was later adjusted based on the results of bacterial cultures. The duration was 48 h on cases of negative results.
Blood routine examination, liver function, and color Doppler ultrasound were performed on days 3, 7, 14, and 30, months 2 and 3, and then every 3 months. Virology, CT, and gastroscopy were performed every 3 months after surgery. Follow-up was censored in October 2014 or at the time of death.
Statistical analysis was performed with SPSS 20.0 (IBM, Armonk, NY, USA). Continuous variables are presented as mean ± standard deviation. Categorical variables are presented as frequencies. The Kaplan-Meier method was used to present overall survival (OS) and disease-free survival (DFS). DFS was defined as the time from initial treatment to the first evidence of recurrence. Survival was censored at the last follow-up. Two-tailed P values <0.05 were considered significant.
Characteristics of the patients
Baseline characteristics of the patients
Values (n = 25)
Age (mean ± SD)
51.52 ± 15.03
Etiology of cirrhosis
HBV + HCV
A 20 (80 %)
B 5 (20 %)
Serum AFP (μg/L)
12 (48 %)
7 (28 %)
6 (24 %)
1 (n = 25)
Tumor size (mm)
20 ± 4.56
17 (68 %)
8 (32 %)
Mean HBV DNA load (log10 IU/mL)
3.10 ± 1.59
Platelet count (×109/L) (mean ± SD)
31.16 ± 6.92
White blood cell count (×109/L) (mean ± SD)
3.81 ± 0.62
ALT (IU/L) (mean ± SD)
41.36 ± 33.76
AST (IU/L) (mean ± SD)
39.80 ± 24.91
Albumin (g/L) (mean ± SD)
41.17 ± 3.68
Bilirubin (μmol/L) (mean ± SD)
15.36 ± 4.99
Length of spleen (cm)
18.36 ± 2.46
Intraoperative and postoperative complications
Converted to open surgery
Infection of port(s)
Postoperative deterioration in liver function tests
Postoperative worsening of ascites
Portal vein thrombosis
No patient had a positive bacterial culture test or became febrile. Portal vein thrombosis occurred in five patients. Three patients had worsening ascites after surgery, two of whom showed increases in bilirubin levels, manifesting the deterioration in liver function. The mean length of stay was 7.0 ± 1.5 days (range 5–15 days). The mean costs of hospitalization were 8064 USD.
Changes in blood cell counts
Recurrence, overall survival, and disease-free survival
Patients (n = 25)
Recently, some studies reported that liver function was improved after splenectomy in patients with portal hypertension and hypersplenism. A study by Shimada et al.  suggested improvements in Child-Pugh scores after splenectomy, while Imura et al.  demonstrated an additional improvement in nutritional metabolism after splenectomy.
Because the residual splenic tissue remaining after partial embolism may regenerate , spleen embolism has not been demonstrated to decrease the total bilirubin levels and may not relieve hypersplenism sufficiently to improve liver function [17, 18]. In addition, the timing of splenectomy is controversial. Hanazaki et al.  and Shimada et al.  suggested that splenectomy should be performed first, followed by hepatectomy, because portal vein thrombosis occurs frequently after synchronous splenectomy and increases the morbidity of the procedure. Meanwhile, Sugawara et al.  suggested that when HCC is located at the left lobe and superficial region of the liver, synchronous splenectomy and liver resection are beneficial because the left lobe is located near the spleen, making the hepatectomy procedure much easier. For tumors located at the right lobe of the liver, they suggested staged splenectomy first and hepatectomy 30 to 58 days later .
Previous studies showed the feasibility of synchronous splenectomy and liver resection without compromising perioperative safety [17, 18, 20–22]. Chen et al.  reported that synchronous open hepatectomy and splenectomy were associated with an improved 5-year DFS.
Synchronous laparoscopic-guided RFA with Lap-sp and endoscopic variceal ligation is safe and feasible, not only minimizing invasiveness but also avoiding spleen regeneration. In this series, no hemorrhage or conversion occurred during the perioperative period. In the previous studies, the mean operative time and blood loss were 103–305 min and 380–1300 mL, respectively [6, 17, 18, 20–22]. In the current study, they were 128 ± 18 min and 206 ± 57 mL, respectively, suggesting that this approach could significantly reduce both parameters. Patients also had a shorter length of stay without compromising safety (7 vs. 13.2 days) .
The frequency of portal vein thrombosis after splenectomy has been reported to range from 2 to 48 % in patients with cirrhosis or portal hypertension , and 50 % in non-cirrhotic patients . The prevalence of operative mortality from portal vein thrombosis after splenectomy ranged from 0 to 18 % [17, 19], compared to 20 % in this present study. The diameter of the splenic vein, low white blood cell counts, and spleen weight were reported as being independent risk factors for portal vein thrombosis . Regarding portal vein thrombosis, the risk factors should be more strictly evaluated, managed, and treated in a future study.
High bilirubin levels secondary to hypersplenism is caused by an increase in bilirubin production, which overloads the capacity of the liver to metabolize bilirubin . Splenectomy might contribute to the decrease of total bilirubin levels, but it is difficult to demonstrate any direct contribution, and postoperative care to protect liver function could also have some influence. Splenectomy has been suggested for the treatment of secondary hypersplenism and thrombocytopenia . Some investigators have carried out splenectomy for patients who had undergone liver transplantation complicated by persistent thrombocytopenia . Takayama et al.  and Sugawara et al.  used this procedure to extend the patient selection criteria for HCC resection in cirrhotic patients.
Previous studies showed that the 1-year survival of patients who underwent simultaneous liver resection and splenectomy is 82–90 % [6, 17, 18, 20–22] and that the 1-year DFS is 80 % [6, 22], which are similar to this present series. However, in the study by Chen et al. , the 5-year DFS was significantly higher. Future studies may help to clarify these issues.
This study was a retrospective and uncontrolled pilot study comparing using previously reported results as comparator. Prospective studies of Lap-sp and splenectomy for HCC patients are necessary.
In conclusion, laparoscopic-guided ablation with Lap-sp and endoscopic variceal ligation could be an elective technique for patients with HCC <3 cm, hypersplenism, and esophagogastric varices. The approach seems to minimize the risks and to result in a fast recovery of the platelet count with an acceptable rate of complications. Although the long-term outcomes after this procedure remain to be determined, future randomized controlled prospective studies are needed to confirm these findings.
DFS, disease-free survival; HCC, hepatocellular carcinoma; Lap-sp, laparoscopic splenectomy; OS, overall survival; RFA, radio-frequency ablation
This work was supported by Science and Technology Planning Project of Guangdong Province, China, 2014A020212715.
Availability of data and materials
Our data will not be shared temporarily because the data will be used in another study of our series research about laparoscopic splenectomy.
KH, QW, SX, ZX, HH, RX, and MD carried out the study and drafted the manuscript. KH, PL, and ZY carried out the data collection. KH and CW participated in the design of the study and performed the statistical analysis. BL conceived of the study, participated in its design and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for the publication of this report and any accompanying images.
Ethics approval and consent to participate
Informed contents were accepted and signed off by all patients and their family members before surgery.
The study was approved by the Committee of Ethics of the Third Affiliated Hospital of Sun Yat-sen University.
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- Li C, Zhao H, Zhao J, Li Z, Huang Z, Zhang Y, et al. Prognosis of patients with hepatocellular carcinoma and hypersplenism after surgery: a single-center experience from the People’s Republic of China. Onco Targets Ther. 2014;7:957–64.PubMedPubMed CentralGoogle Scholar
- Yao Z, Hu K, Huang P, Huang H, Chen X, Yang P, et al. Delayed laparoscopic cholecystectomy is safe and effective for acute severe calculous cholecystitis in patients with advanced cirrhosis: a single center experience. Gastroenterol Res Pract. 2014;2014:178908.View ArticlePubMedPubMed CentralGoogle Scholar
- Morise Z, Kawabe N, Tomishige H, Nagata H, Kawase J, Arakawa S, et al. Recent advances in the surgical treatment of hepatocellular carcinoma. World J Gastroenterol. 2014;20(39):14381–92.View ArticlePubMedPubMed CentralGoogle Scholar
- Han DH, Choi GH, Park JY, Ahn SH, Kim KS, Choi JS, et al. Lesson from 610 liver resections of hepatocellular carcinoma in a single center over 10 years. World J Surg Oncol. 2014;12:192.View ArticlePubMedPubMed CentralGoogle Scholar
- Clinical Practice Guidelines in Oncology (NCCN Guidelines). Hepatobiliary cancers. Version 2.2015. Fort Washington: National Comprehensive Cancer Network; 2015.Google Scholar
- Chen XP, Wu ZD, Huang ZY, Qiu FZ. Use of hepatectomy and splenectomy to treat hepatocellular carcinoma with cirrhotic hypersplenism. Br J Surg. 2005;92(3):334–9.View ArticlePubMedGoogle Scholar
- Tomikawa M, Akahoshi T, Sugimachi K, Ikeda Y, Yoshida K, Tanabe Y, et al. Laparoscopic splenectomy may be a superior supportive intervention for cirrhotic patients with hypersplenism. J Gastroenterol Hepatol. 2010;25(2):397–402.View ArticlePubMedGoogle Scholar
- Fang Y, Chen W, Liang X, Li D, Lou H, Chen R, et al. Comparison of long-term effectiveness and complications of radiofrequency ablation with hepatectomy for small hepatocellular carcinoma. J Gastroenterol Hepatol. 2014;29(1):193–200.View ArticlePubMedGoogle Scholar
- Hasegawa K, Kokudo N, Makuuchi M, Izumi N, Ichida T, Kudo M, et al. Comparison of resection and ablation for hepatocellular carcinoma: a cohort study based on a Japanese nationwide survey. J Hepatol. 2013;58(4):724–9.View ArticlePubMedGoogle Scholar
- Shi J, Sun Q, Wang Y, Jing X, Ding J, Yuan Q, et al. Comparison of microwave ablation and surgical resection for treatment of hepatocellular carcinomas conforming to Milan criteria. J Gastroenterol Hepatol. 2014;29(7):1500–7.View ArticlePubMedGoogle Scholar
- Akahoshi T, Hashizume M, Tanoue K, Shimabukuro R, Gotoh N, Tomikawa M, et al. Role of the spleen in liver fibrosis in rats may be mediated by transforming growth factor beta-1. J Gastroenterol Hepatol. 2002;17(1):59–65.View ArticlePubMedGoogle Scholar
- Arakawa Y, Shimada M, Uchiyama H, Ikegami T, Yoshizumi T, Imura S, et al. Beneficial effects of splenectomy on massive hepatectomy model in rats. Hepatol Res. 2009;39(4):391–7.View ArticlePubMedGoogle Scholar
- Lin N, Liu B, Xu RY, Fang HP, Deng MH. Splenectomy with endoscopic variceal ligation is superior to splenectomy with pericardial devascularization in treatment of portal hypertension. World J Gastroenterol. 2006;12(45):7375–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Shimada M, Hashizume M, Shirabe K, Takenaka K, Sugimachi K. A new surgical strategy for cirrhotic patients with hepatocellular carcinoma and hypersplenism. Performing a hepatectomy after a laparoscopic splenectomy. Surg Endosc. 2000;14(2):127–30.View ArticlePubMedGoogle Scholar
- Imura S, Shimada M, Utsunomiya T, Morine Y, Ikemoto T, Mori H, et al. Impact of splenectomy in patients with liver cirrhosis: results from 18 patients in a single center experience. Hepatol Res. 2010;40(9):894–900.View ArticlePubMedGoogle Scholar
- Lee CM, Leung TK, Wang HJ, Lee WH, Shen LK, Liu JD, et al. Evaluation of the effect of partial splenic embolization on platelet values for liver cirrhosis patients with thrombocytopenia. World J Gastroenterol. 2007;13(4):619–22.View ArticlePubMedPubMed CentralGoogle Scholar
- Sugawara Y, Yamamoto J, Shimada K, Yamasaki S, Kosuge T, Takayama T, et al. Splenectomy in patients with hepatocellular carcinoma and hypersplenism. J Am Coll Surg. 2000;190(4):446–50.View ArticlePubMedGoogle Scholar
- Wu CC, Cheng SB, Ho WM, Chen JT, Yeh DC, Liu TJ, et al. Appraisal of concomitant splenectomy in liver resection for hepatocellular carcinoma in cirrhotic patients with hypersplenic thrombocytopenia. Surgery. 2004;136(3):660–8.View ArticlePubMedGoogle Scholar
- Hanazaki K, Kajikawa S, Adachi W, Amano J. Portal vein thrombosis may be a fatal complication after synchronous splenectomy in patients with hepatocellular carcinoma and hypersplenism. J Am Coll Surg. 2000;191(3):341–2.View ArticlePubMedGoogle Scholar
- Oh JW, Ahn SM, Kim KS, Choi JS, Lee WJ, Kim BR. The role of splenectomy in patients with hepatocellular carcinoma and secondary hypersplenism. Yonsei Med J. 2003;44(6):1053–8.View ArticlePubMedGoogle Scholar
- Kim SH, Kim do Y, Lim JH, Kim SU, Choi GH, Ahn SH, et al. Role of splenectomy in patients with hepatocellular carcinoma and hypersplenism. ANZ J Surg. 2013;83(11):865–70.View ArticlePubMedGoogle Scholar
- Wang C, Li C, Wen TF, Yan LN, Li B, Liang GL, et al. Safety of synchronous hepatectomy and splenectomy for patients with hepatocellular carcinoma and hypersplenism. Hepatogastroenterology. 2012;59(114):526–8.View ArticlePubMedGoogle Scholar
- Zhang Y, Wen TF, Yan LN, Yang HJ, Deng XF, Li C, et al. Preoperative predictors of portal vein thrombosis after splenectomy with periesophagogastric devascularization. World J Gastroenterol. 2012;18(15):1834–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Ikeda M, Sekimoto M, Takiguchi S, Kubota M, Ikenaga M, Yamamoto H, et al. High incidence of thrombosis of the portal venous system after laparoscopic splenectomy: a prospective study with contrast-enhanced CT scan. Ann Surg. 2005;241(2):208–16.View ArticlePubMedPubMed CentralGoogle Scholar
- Kinjo N, Kawanaka H, Akahoshi T, Tomikawa M, Yamashita N, Konishi K, et al. Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension. Br J Surg. 2010;97(6):910–6.View ArticlePubMedGoogle Scholar
- 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(7):1043–8.PubMedGoogle Scholar
- Coon WW. Splenectomy for thrombocytopenia due to secondary hypersplenism. Arch Surg. 1988;123(3):369–71.View ArticlePubMedGoogle Scholar
- Cescon M, Sugawara Y, Takayama T, Seyama Y, Sano K, Imamura H, et al. Role of splenectomy in living-donor liver transplantation for adults. Hepatogastroenterology. 2002;49(45):721–3.PubMedGoogle Scholar