Hepatocellular carcinoma accompanied by hypersplenism : five cases of simultaneous hepatectomy and laparoscopic

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Hepatocellular carcinoma accompanied by hypersplenism : five cases of simultaneous hepatectomy and laparoscopic

splenectomy

Yasuyuki Nakata, Seiji Haji, Mithuo Yamasaki, Takuya Nakai and

Hajime Ishikawa,

Yoshihumi

Department of Surgery, Kinki University

Osakasayama, Osaka,

Takeyama

Faculuty of

589-8511, Japan

Takeo

Medicine,

Yasuda,

Abstract

Background : We performed simultaneous hepatectomy and laparoscopic splenectomy in a patient with hepatocellular carcinoma ac-

companied by a reduced platelet count caused by hypersplenism.

Methods : We retrospectively studied 5 cases of hepatectomy performed immediately after laparoscopic splenectomy at our hospital after July 2006, and evaluated the intraoperative blood loss, need for transfusion during surgery, pos-

toperative complications, and postoperative hospital stay. Hematological analysis included the

white blood cell count (WBC), platelet count (Plt), serum alanine transaminase (ALT), total serum bilirubin (T-Bil), prothrombin time (PT)%, and serum albumin (Alb). Analysis was performed on postoperative days (POD) 7, 14, 30,

and 60.

Results : The results showed intraoperative

Introduction

In Japan, the majority of hepatocellular carcinoma cases are accompanied by chronic viral hepatitis and cirrhosis. When cirrhosis is present, hypersplenism causes secondary thrombocytopenia, often making interferon treatment of hepatitis and chemotherapy after the recur- rence of hepatocellular carcinoma difficult. In recent years, many institutions perform splenectomy because of its efficacy in patients with cirrhosis accompanied by throm-

blood loss of 891+523.2 ml (mean+ SD, 35-2, 199), blood transfusion in 3 cases (60%), no complications in all cases, and a postoperative hospital stay of 11.8 (11-13) days. Compared with preoperative levels, WBC and Plt were significantly higher on POD 7, 14, 30, and 60.

while ALT and T-Bil were significantly lower on POD 30. Alb levels were low on all postoperative days compared with preoperative levels.

There were no significant changes in PT%.

Conclusions : It was safe to conduct hepatectomy simultaneously with laparoscopic splenectomy. No significant liver dysfunction occurred postoperatively, suggesting a potential reduction in the patient burden.

Key words : patocellular splenectomy

hypersplenism, carcinoma,

cirrhosis, he- hepatectomy,

bocytopenia. When hepatocellular carcinoma and thrombocytopenia due to cirrhosis are present, splenectomy or partial splenic embolization (PSE) is performed to increase the platelet count prior to hepatectomy or percutaneous radiofrequency ablation. Because of safety concerns, a relatively small number of simultaneous splenectomy and hepatectomy procedures have been performed, most of which were done in open surgery,7-1° and only a few cases involved laparoscopy.11 The safety of laparoscopic splenectomy has improved in recent years, and

Received May 10, 2011 ; Accepted June 2, 2011

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the procedure has fewer complications than open abdominal surgery. With hand-assisted laparoscopy, it is possible to reduce the duration of surgery and intraoperative blood loss. For these reasons, in patients with hepatocellular carcinoma accompanied by thrombocytopenia, we performed hepatectomy immediately after laparoscopic splenectomy. Here, we present a report of 5 cases.

Materials and Methods

Clinical cases and evaluation items

Since July 2006, we have performed simultaneous hepatectomy and splenectomy by laparoscopy in 5 cases, and have evaluated the efficacy of the procedure as described below. At our institution, the indication for splenectomy is a platelet count of <7>< 10-4 in a patient who requires interferon treatment because of a high hepatitis viral load or who is a candidate for hepatectomy due to the presence of hepatocellular carcinoma. Study items were intraoperative blood loss, presence or absence of blood transfusion during surgery, postoperative complications, and postoperative hospital stay.

Hematological analysis included the white blood cell count (WBC), platelet count (Plt), serum alanine transaminase (ALT), total serum bilirubin (T-Bil), prothrombin time (PT)%, and serum albumin (Alb). Analysis was performed on postoperative days (POD) 7, 14, 30, and 60.

Surgical technique

In all cases, 20 units of platelets were adminis- tered before surgery, and splenectomy was performed using laparoscopy on a patient in the semirecumbent position to the right. An incision (7 cm) along the midline was made to mount the GelPort® (Applied Medical, CA, USA). A small opening was made in the lower left umbili- cal area for the insertion of a camera, and two openings were made below the left rib cage and in the left abdominal area for a 12-mm port (Fig.

1). We observed the abdominal cavity to ensure the absence of splenculus, opened the omental bursa on the left and separated the gastrosplenic ligament, and made an incision in the proximity of the upper splenic pole. We dissected the splenocolic ligament without processing the short gastric vessels near the upper splenic pole, because they are potential bleeding points.

These blood vessels were transected after the spleen was separated from the retroperitoneum

Solenectomy Open abdominal surgery

Rigfitsemirerun-bent position Supine position

—skin intisbn :port site

Fig. 1 Hepatectomy performed through an extended incision in the supine position after laparoscopic

splenectomy in the right semirecumbent position. In

case 5, liver mobilization was performed by laparos-

copy without extending the original incision.

and mobility improved. Tissues were separated using an ultrasonic coagulation cutting device (Harmonic Scalpel®, Ethicon Endo-Surgery Inc., Tokyo, Japan), LigaSure® (Tyco Healthcare Japan, Tokyo, Japan), and a hook electrocautery probe. The splenic hilum was dissected using a stapler in all cases, and the spleen was placed in a plastic bag and enucleated through the midline incision. The patient was then placed in the supine position and the original incision was extended for hepatectomy (Fig. 1). In cases 1-4, a transverse incision to the right was made from the original incision, resulting in a final inverted L-shaped incision. In case 5, because the location of the tumor was near the lateral segment of the liver, mobilization of the liver was performed by laparoscopy and resection was made through the original 7-cm incision. In all cases of hepatectomy, the Pringle method was used to perform inflow occlusion. The hepatic capsule was resected with an ultrasonic coagulation cutting device, and the hepatic parenchyma was resected with a cavitron ultrasonic surgical aspirator and a dissecting sealer (TissueLinkTM monopolar device, TissueLink Medical Inc., NH, USA). In case 1, we also performed radiofrequency ablation (Table 1).

Post-discharge follow-up

After discharge, blood sampling and clinical examination were performed on POD 14 and 60.

On POD 30, in addition to blood sampling, computed tomography (CT) angiography was performed to ensure the absence of portal vein thrombosis. In all cases, pneumococcal vaccine was given on POD 30.

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Table 1 Background and progress of patients before and after surgery.

Age/ Child- Location Gender/ Pugh/ of tumor BMI(kg/m2)/ ICG(%) ( X number

VM of tumors)

Operation Operation time(min)

Bleeding Weight of Stage Postoperative (m1) spleen(g) hospital stay

1 66/

F/

20.5/

HCV

A/24 S3 X 1 S4 X 1 S7 X 1

HALS-S P • H(S3/7)

RFA(S4)

375 774 480 TTT 12

2 57/

M/

24.9/

HCV

A/26 S8 X 3 S6 X 1 S4 X 2

HALS-S P•H

445 2199 (Transfusion)

840 III 11

3 69/

M/

26.7/

None

A/14 S5 X 1 HALS-S P•H

370 I 13

4 61/

F/

22.1/

HCV

A/26 S6 X 1 HALS-S

P•H

306 35 900 I 11

5 72/

M/

19.1/

HCV

A/14 S3 X 2 HALS-S L•H

250 ITI 12

VM : Virus Marker ; S : Couinaud's Classification of Splenectomy of Hand assisted Laparoscopic Surgery ; Radio-frequency Ablation.

the liver ; P•Hr : Partial Hepatectomy ; HALS-S : L•Hr : Lateral Segmentectomy of the Liver ; RFA :

Statistics

Statistical analysis was performed using Stu- dent's t-test. The results are expressed as the mean+ SD, and were considered significant when p< 0.05.

Results

The patients were 3 males (60%) and 2 females (40%) aged 65±4.8 (57-72) years old (Table 1).

The average body mass index was 22.66±2.512 (19.1-26.7). Four patients (80%) had chronic hepatitis C, and 1 (20%) was negative for hepatitis infection. The Child-Pugh classification was A in all cases, and the indocyanine green clear- ance rate was 20.8 ± 5.44 (14-26)%. The average number of tumors per patient was 2.6 (1-6). A tumor was located in both lobes in 2 cases (40%), in the right lobe only in 2 cases (40%), and in the left lobe only in 1 case (20%). Surgery time was 389+48.5 (306-445) min. Blood loss was 891+

523.2 (35-2199) ml, and blood transfusion was

performed in 3 cases (60%). The weight of the spleen was 568± 241.6 (250-900) g. With regard to the degree of tumor progression, 2 patients were Stage I (40%) and 3 were Stage III (60%).

During the postoperative course of all patients, no complications were observed, and the postoperative hospital stay was 11.8 (11-13) days (Table 1).

Hematology results showed that the levels of WBC and Plt were significantly higher on POD 7, 14, 30, and 60 compared with preoperative levels (Table 2). ALT levels were significantly lower on POD 30 only. Overall, T-Bil levels were lower than preoperative levels throughout the study period, attaining significance on POD 30. On POD 60, none of the patients had a T-Bil level above the preoperative level. There were no significant differences in PT% between the POD groups. Compared with preoperative levels, Alb levels were significantly lower at all measurement points. In all 5 cases, no portal vein thrombosis was detected by CT angiogra-

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Table 2 Hematological analysis results (mean± SD) ; * : P < 0.05 vs . preoperative levels . Pre

Operation

POD 7 POD 14 POD 30 POD 60

WBC(/mm3) 3,140+ 792 10,320+ 2,224* 7,400+ 440* 7,000+ 920* 6,960+ 1,088*

Plt( X 104/mm3) 4.62+0.856 26.56+ 5.744* 33.9+6.8* 27.44+ 5.288* 20.96+4.008*

ALT(IU/1) 51+ 7.6 59.6+ 17.92 55.2+ 32.64 34.6+ 12.32* 36.6+ 12.08

T-Bil(mg/dl) 1.16+0.128 1.16+0.288 0.88+0.264 0.82 + 0.224* 0.78+0.264

PT(%) 77.04+ 8.448 73.9 + 2.96 74.44+ 5.352 75.5 + 7.76 78.82±6.216

Alb(g/dl) 3.98+ 0.144 2.72 + 0.144* 2.94+0.208* 3.26+0.248* 3.42 + 0.136*

phy taken on POD 30.

Discussion

This study aimed to elucidate if hepatectomy can be performed immediately following laparoscopic splenectomy in patients with throm- bocytopeni a due to cirrhosis. Besides splenectomy, PSE is performed to increase the platelet count and is easy to perform and less invasive than splenectomy, demonstrating its clinical efficacy.2,3 On the other hand, complications such as high fever, pain, splenic abscess, bacterial peritonitis, hepatic failure, and multi- ple organ failure have been reported. Because the efficacy of PSE lasts approximately 1 year and because it is necessary to perform PSE sev- eral times to obtain its full effect, PSE is current- ly not fully supported.4'5 For this reason, we decided to perform splenectomy because of its reliable end result. In addition, because of improvements in surgical procedures and tech- niques in recent years, resection of the spleen can be achieved safely using a laparoscopic method regardless of the primary disease.L8 Although it was possible to carry out complete laparoscopic splenectomy, we decided to make an inverted L- shaped incision for hepatectomy and performed splenectomy under hand-assisted laparoscopy in all cases. Patients with cirrhosis tend to bleed easily because of an impaired coagulation capac- ity and the presence of portal hypertension that results from the development of collateral circu- lation. Therefore, splenectomy under hand-assisted laparoscopy is believed to be safer should manual hemostasis need to be applied to stem bleeding.

In general, splenectomy is performed prior to hepatectomy. According to a study by Shimada et al. on 6 cases of hepatocellular carcinoma in which splenectomy was performed before he-

patectomy,7 a significant increase in WBC and Plt and improvement in the Child-Pugh classification were observed. In addition, platelet transfusion was not necessary prior to hepatectomy, and the amount of bleeding was less compared with cases of hepatectomy without prior splenectomy.7 Our data revealed 891 ± 523.2 (35- 2,199) ml of intraoperative blood loss, 3 cases (60%) of transfusion, no postoperative complications, and 11.8 (11-13) days of postoperative hospital stay. Simultaneous resection of the liver and spleen in open surgery, using the same procedures as those employed in this study, were performed in 12 cases by Takayama et al.,8 35 by Sugawara et al.,' 94 by Chen et al.," and 10 by Shimada et al.' (Table. 3). It may not be appro- priate to compare our data with theirs because of a relatively low sample number in this study ; however, considering the absence of complications and the short hospital stay seen in the present study, we can conclude that the procedures used in this study are safe. With regard to transfusion, Chen et al. performed no transfusion in 66 of 94 cases (70.2%)."

The significant increase in WBC and Plt compared with the preoperative levels resulted from the absence of hemolysis after splenectomy.

WBC/Plt levels in previous studies were also significantly increased.7-9 Because there were no significant changes in ALT, T-Bil, and PT%

compared with preoperative levels, it is clear that the liver function is not significantly affected by the procedures used in this study.

The effect of splenectomy on the liver function has been gathering attention in recent years ; however, no consensus has been reached and further studies are needed to elucidate if similar effects can be obtained under stressful conditions such as undergoing simultaneous hepatectomy.

According to Chen et al., the 5-year tumor-free survival rate was extended in patients who under-

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Table 3 The reported cases of Simultaneous simultaneous hepatectomy and splenectomy.

Number of cases

Age(Year) (mean± S.D)

Operation Bleeding

(ml)

Complication (%)

Takayame 12 54.0+ 3.0 1,223+ 153 n.d

Sugawara9) 34 58.0+ 1.0 (1) 1,156+159 50.0

Chen'°) 94 44.6+ 10.2 380+ 220 15.9

Shimoda') 10 62.5+6.3 700-6,700

(average 2,451)

n.d

Kitami" 1 63.0 840(g) ⁰

n.d

Open simultaneous hepatectomy and splenectomy.

Simultaneous open hepatectomy and laparoscopic splenectomy.

Simultaneous laparoscopic hepatectomy and splenectomy.

: not description

went simultaneous hepatectomy and splenectomy compared with those who under- went hepatectomy only. Interestingly, the ratio of CD4/CD8 (subsets of T cells) increased significantly,10 suggesting the possibility that the removal of the spleen enhances antitumor immu- nity.

Postoperative blood loss, pancreatic fistula, portal vein thrombosis, and overwhelming severe postsplenectomy infection are known complications of splenectomy, among which portal vein thrombosis is known to affect the postoperative liver function. Portal vein thrombosis needs to be seriously considered because it reportedly occurs in 25-68.4% of patients with portal hypertension." Accordingly, some studies have reported the use of anticoagulants immediately following surgery ; however, such treatment may increase the chance of recurrent bleeding from an excision site in the case of simultaneous liver and spleen resection. Prior to this study, we decided to abstain from postoperative anticoagulation therapy and prescribe antiplatelet drugs if thrombosis was found on CT angiography on POD 30.

It should be noted that there is a report on extensive portal vein thrombosis following simultaneous hepatectomy and splenectomy in open surgery.12 It is necessary to further study the effect of anticoagulant therapy following simultaneous hepatectomy and splenectomy.

Hepatectomy was performed an average of 19 (7-40) days' or 33± 2 days8 after splenectomy in studies that conducted splenectomy and hepatectomy separately. The significance of simultaneous resection is expected to be high considering the potential progression of disease and

emotional distress of patients during the waiting period between surgery and the increase in medical expense on 2 separate operations.

Conclusion

We encountered 5 cases of hepatocellular carcinoma accompanied by hypersplenism and conducted hepatectomy immediately following laparoscopic splenectomy. The safety of the simultaneous resection procedure was satisfac- tory, and there was no significant decrease in the liver function. Our study clearly suggests the potential alleviation of the burden and pain of patients.

Conflict of interest statement

Yasuyuki Nakata and other co-authors have no conflict of interest.

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