World J Surg (2014) 38:1141–1146 DOI 10.1007/s00268-013-2380-3

Feasibility of Laparoscopic Re-resection for Patients with Recurrent Hepatocellular Carcinoma Albert C. Y. Chan • Ronnie T. P. Poon • Kenneth S. H. Chok • Tan To Cheung • See Ching Chan • Chung Mau Lo

Published online: 5 December 2013 Ó Socie´te´ Internationale de Chirurgie 2013

Abstract Background Repeated resection via an open approach is an effective treatment for post-operative recurrent hepatocellular carcinoma (HCC). However, there are limited data on the application of laparoscopic approach for recurrent HCC in patients with prior liver resections. The aim of this study was to review our experience of laparoscopic reresection in patients with postoperative tumor recurrence. Materials and methods A total of 11 patients received laparoscopic re-resections for postoperative tumor recurrence in our center. Data were reviewed for demographics, tumor characteristics, and perioperative outcomes. Casematch analysis with the open approach was performed in a 1:2 ratio. Results Six patients had their first liver resection carried out via the open approach and the remaining five patients received the laparoscopic approach. The recurrent tumor size was 20 mm (12–50 mm) and ten patients had a solitary recurrence. Two patients had laparoscopic left lateral sectionectomy and the remaining nine patients had subsegmentectomies. There was no significant difference in patient characteristics, preoperative liver function, and tumor features between the laparoscopic and open groups.

A. C. Y. Chan (&)  R. T. P. Poon  K. S. H. Chok  T. T. Cheung  S. C. Chan  C. M. Lo Division of Hepatobiliary and Pancreatic Surgery, and Liver Transplantation, Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, Hong Kong e-mail: [email protected] R. T. P. Poon  S. C. Chan  C. M. Lo State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, Hong Kong

Perioperative blood loss was significantly reduced in the laparoscopic group (100 vs. 314 mL; p = 0.014) but the morbidity rate (18.2 vs. 4.5 %; p = 0.199) and length of hospitalization were comparable (6 vs. 5 days; p = 0.831). The 3-year overall survival rates for the laparoscopic and open groups were 60.0 and 89.3 %, respectively (p = 0.279). Conclusion Our study showed that laparoscopic reresection for recurrent HCC was feasible with satisfactory postoperative and oncological outcomes, even in patients with previous major liver resections.

Background Liver resection is a curative treatment for hepatocellular carcinoma (HCC) in patients with well-preserved liver function or Child-Pugh A cirrhosis. However, the oncological outcome of liver resection is often undermined by frequent tumor recurrence, with a reported 5-year recurrence rate of 50–70 % [1–3]. Recurrence in liver remnant accounts for about 80 % of patients with postoperative recurrence [3], and so further salvage treatment is often anticipated [4]. Repeated resection has been shown to be an efficacious treatment for recurrent HCC with an acceptably low morbidity and mortality rate [5–7]. With the introduction of laparoscopic liver resection in recent years, satisfactory short- and long-term oncological outcomes have been reported by various studies [8–10]. However, there are still limited data on the application of laparoscopic surgery to repeated resection for recurrent HCC in patients with prior liver resections. The aim of this study was to review our preliminary experience of laparoscopic re-resection in patients with postoperative tumor recurrence.

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Methods A total of 11 patients received laparoscopic re-resection from January 2004 to 2013 in the Department of Surgery, Queen Mary Hospital, Hong Kong. There were no cases of conversion. Data regarding patient demographics, primary and recurrent tumor characteristics, and perioperative outcomes were retrieved from our prospectively collected database of over 1,000 patients with resectable HCC. Nomenclature for the anatomical liver resection was described according to the Brisbane classification [11]. To further analyze the short-term and oncological benefit of laparoscopic re-resection, the cohort were matched with patients who received open re-resection for age, gender, tumor size, and location in a 1:2 ratio. Surveillance and diagnosis of post-operative recurrent HCC All patients underwent contrast-enhanced computed tomography with measurement of serum alpha-fetoprotein (AFP) and liver biochemistry at 1 month after resection of primary HCC to confirm complete tumor clearance. The same set of investigations was repeated at 3-monthly intervals for tumor surveillance in the first 2 years after resection, and then at 6-monthly intervals thereafter. Intrahepatic recurrence is defined as a new lesion with arterial contrast enhancement and portal venous washout according to the latest American Association for the Study of Liver Disease (AASLD) guidelines [12]. Inclusion criteria for laparoscopic re-resection The selection criteria for re-resection in our center were as follows: Child-Pugh A cirrhosis, absence of gross ascites, and a platelet count C100 9 109 L-1. Regarding tumor features, laparoscopic re-resection was considered for solitary subcapsular or pedunculated tumor growth in left liver (segment II, III, IVb) or right liver (segment V or VI). Operative techniques for laparoscopic re-resection Nine patients were placed in the lithotomy position and two patients in the right decubitus position. An open cutdown technique to introduce the camera port was preferred in order to avoid potential injury to bowel adhering to the anterior abdominal wall. Pneumoperitoneum was maintained at a pressure between 12 and 14 mmHg. Intraoperative ultrasound was routinely performed to ascertain the location of the tumor and to exclude additional tumors in the liver remnant. Parenchymal transection was performed using a Cavitron ultrasonic surgical aspirator (CUSA, Valleylab, Boulder, CO, USA) and/or Sonosurg

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(Olympus). Large bile duct branches or vessels were clipped before division and minor hemostasis was carried out using bipolar diathermy. Large segmental hepatic vein branches were divided by endovascular staplers. The Pringle maneuver was not required in our patients. The specimen was retrieved in a bag in one piece. No drain was inserted. Intraoperative assessment of the level of adhesions The level of adhesions was graded as minimal (no sharp dissection required for adhesiolysis), moderate (sharp dissection required for adhesiolysis), and severe (abundant vascular adhesions that required lysis by Sonosurg and/or diathermy). All continuous varies were expressed in median (range) and compared between groups using the Mann–Whitney U test. Categorical variables were expressed in absolute number (percentage) and compared between groups using the Chi squared test. Survival analysis was conducted using the Kaplan–Meier method and compared between groups using the log-rank test. A p value \0.05 was considered to be statistically significant. All statistical analysis was performed using SPSS version 20.0.

Results Table 1 lists the pre- and perioperative details of each patient. The median age of our patients was 63 years (43–80 years). Seven patients had hepatitis B-related HCC, one patient had hepatitis C-related HCC, and three patients had no viral etiology. All patients had Child-Pugh A liver cirrhosis, except for two patients with normal livers and one patient with steatosis. The preoperative indocyanine green (ICG) clearance rate at 15 min before laparoscopic re-resection was 13.8 % (5.0–32.0), and serum platelet count was 138 9 109 L-1 (103–222). The primary tumor size was 45 mm (20–140); all were solitary tumors. The types of liver resections for primary HCC were right hepatectomy (n = 3), right trisectionectomy (n = 1), segmentectomy (n = 2), and sub-segmentectomy (n = 5). Six patients had their first liver resection done via the open approach and the remaining five patients received the laparoscopic approach. The time to recurrence was 21 months (5–125) and the serum AFP level at the time of recurrence was 6 ng mL-1 (2–3,985). The recurrent tumor size was 20 mm (12–50), and ten patients had solitary recurrence. Two patients had a laparoscopic left lateral sectionectomy and the remaining nine patients had sub-segmentectomies. The perioperative blood loss was 100 mL (10–600); no patients required blood transfusion. Intra-abdominal adhesions for patients

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Table 1 Primary and recurrent tumor characteristics and choice of resections Patient

Age (years)

PTS (mm)/location

PR

RTL

RTS (mm)

L re-resection

Level of adhesions

Aa

43

95/V–VIII

RT/O

III

20

SS

Moderate

B

80

23/VI

S/L

II ? III

50

LLS

Minimal

C

51

45/III

SS/L

V

15

SS

Minimal

D

64

23/V

SS/L

IV

50

SS

Minimal

E

63

20/V

SS/O

V

40

SS

Moderate

F

52

140/V–VIII

RH/O

II

15

SS

Moderate

G

55

20/VI

S/L

VII

19

SS

Moderate

H

51

20/V

SS/L

II ? III

12

LLS

Severe

I

63

140/V–VIII

RH/O

II

25

SS

Minimal

J

63

100/V–VIII

RH/O

II ? III

20

SS

Minimal

Kb

77

45/VII–VIII

SS/O

II ? III

30

SS

Moderate

HCC hepatocellular carcinoma, L laparoscopic approach, LLS left lateral sectionectomy, O open approach, PR type of first resection for primary HCC, PTS primary tumor size, RH right hepatectomy, RT right trisectionectomy, RTL recurrent tumor location, RTS recurrent tumor size, S segmentectomy, SS sub-segmentectomy a

Postoperative bile leak

b

Postoperative atrial fibrillation

Recovery of liver function

Fig. 1 Significant omental adhesions to the undersurface of left lateral section and tumor surface

who had open resection for the primary tumor (n = 6) were regarded as minimal (n = 2) and moderate (n = 4), and for those who had laparoscopic resection of the primary tumor (n = 5) adhesions were minimal (n = 3), moderate (n = 1), and severe (n = 1) (Fig. 1). In the one case with severe adhesions, the greater omentum and the right cirrhotic liver was noted as adhering to the anterior abdominal wall. Extensive adhesiolysis was required before a left lateral sectionectomy was completed. The median operating time was 190 min (131–352). The median resection margin was 10 mm (5–15). One patient received two episodes of open wedge resections of segment V for the primary and first-time recurrent tumor before receiving a laparoscopic sub-segmentectomy for the second-time recurrence in segment II.

The serum bilirubin and serum aspartate aminotransferase peaked on postoperative day 1 in six (54.5 %) and seven patients (63.6 %), respectively. All patients showed a normalizing trend of serum bilirubin level from postoperative day 3 and of serum aspartate aminotransferase from postoperative day 2 onwards. The postoperative morbidity rate was 18.2 % (2 of 11 patients). One patient developed atrial fibrillation postoperatively and the other patient developed bile leakage from the transection surface after laparoscopic resection of segment III recurrence that required laparotomy for repair on postoperative day 8. His recovery after the reoperation was uneventful and he was discharged on postoperative day 23. The median duration of hospital stay of our patients was 7 days (5–23). For those who had uneventful recovery without postoperative morbidity (n = 9), the median duration of hospital stay was reduced to 6 days (5–10). Re-resection: laparoscopic versus open approach There was no significant difference in patient characteristics, preoperative liver function, tumor size, and number between the two groups (Tables 2, 3). Perioperative blood loss was significantly reduced in the laparoscopic group when compared with the open group (100 vs. 314 mL; p = 0.014). There was no hospital mortality. One patient (4.5 %) in the open group developed subphrenic collection that was managed conservatively. There was no significant difference in length of hospital stay (p = 0.831) and postoperative morbidity rate (p = 0.199) between the two

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Table 2 Patient characteristics and preoperative liver function Characteristic

Laparoscopic re-resection (n = 11)

Open re-resection (n = 22)

Age, years

61 (43–80)

62 (43–76)

0.716

Gender (M:F)

8:3

16:6

1.000

HBsAg Anti-HCV

7 (63.6) 1 (9.1)

18 (81.8) 2 (9.1)

0.391 0.930

Table 3 Tumor characteristics and perioperative details

p value

Co-morbid illness

4 (36.4)

8 (36.4)

1.000

Cardiovascular

3 (27.3)

6 (27.3)

1.000

Laparoscopic re-resection (n = 11)

Open re-resection (n = 22)

p value

Serum AFP (ng mL-1)

6 (2–3985)

5.5 (2–966)

0.530

Tumor size (cm)

2 (1.0–4.5)

2 (1.0–5.0)

0.955

Left lobe

7 (63.6)

14 (63.6)

1.000

Right lobe

4 (36.4)

8 (36.4)

Recurrent tumor location

Respiratory

1 (9.1)

1 (4.5)

1.000

Diabetes mellitus

0 (0)

2 (9.1)

0.542

1

10 (90.9)

20 (90.9)

Gastrointestinal

0 (0)

2 (9.1)

0.542

2

1 (9.1)

2 (9.1)

Serum bilirubin (lmol L-1)

11 (5–17)

11 (5–18)

0.818

Serum creatinine (lmol L-1)

76 (51–114)

77 (51–100)

0.878

Serum albumin (g dL-1)

40 (35–48)

43 (35–48)

0.099

INR

1.1 (0.9–1.2)

1 (0.9–1.2)

0.064

Serum platelet count (9109 L-1)

138 (102–222)

142 (44–241)

0.789

-1

Serum AST (l L ) -1

Serum ALT (l L )

41 (23–72) 29 (11–72)

33 (19–183) 29 (10–172)

No. of tumor nodules 1.000

Resection margin Not involved

11 (100.0)

20 (90.9)

Involved

0 (0)

2 (9.1)

Left lateral segmentectomy

1 (9.1)

0 (0)

Segmentectomy

0 (0)

2 (9.1)

0.542

Type of resection

Sub-segmentectomy

0.223

10 (90.9)

20 (90.9)

0.169

Blood loss (L)

0.1 (0.05–0.5)

0.34 (0.01–1.60)

0.014

0.647

Operative time (min)

200 (131–352)

188 (100–427)

0.939 0.199

Postoperative complications

Data are presented as n (%) or (range) unless otherwise indicated ALT alanine aminotransferase, AST aspartate aminotransferase, HBsAg hepatitis B virus surface antigen, HCV hepatitis C virus, INR international normalized ratio

groups (Table 3). There was also no significant difference in the clearance of resection margin (p = 0.542). The 3-year overall survival rates (Fig. 2) for the laparoscopic and open groups were 60.0 and 89.3 %, respectively (p = 0.279), and the corresponding disease-free survival rates (Fig. 3) were 18.9 and 45.7 %, respectively (p = 0.575).

Discussion Re-resection is an effective treatment for postoperative tumor recurrence. Recent studies have shown the survival benefit of such an aggressive treatment strategy with an acceptably low postoperative morbidity and mortality rate [5, 6, 13]. Concern regarding oncological clearance via the laparoscopic approach may not be justified given the adequate resection margin obtained for our patients. However, one of the technical challenges for surgeons when embarking on re-resection is dealing with densely formed adhesions from previous operations. Adhesiolysis forms an integral part of the operative strategy for reoperation, and only meticulous technique can minimize

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Atrial fibrillation

1

0

Bile leak

1

0

Subphrenic collection

0

1

Hospital stay (days)

6 (3–17)

5 (3–15)

0.831

Data are presented as n (%) or (range) unless otherwise indicated AFP alpha-fetoprotein

bleeding and prevent bowel injury that would have an impact on postoperative morbidity. Nonetheless, adhesions after previous open liver resection may not always be a deterring factor for laparoscopic re-do surgery. In our cohorts, none of the four patients who had previous major right liver resections were identified as having severe adhesions that precluded an attempt at laparoscopic surgery. The pneumoperitoneum could tense up the adhesion bands that would facilitate a more precise dissection during lysis of adhesions. Furthermore, the high-resolution view offered by laparoscopy due to advances in high-definition optical technology in recent years has greatly enhanced the visual preciseness in identifying vital structures, especially in areas obscured by highly vascularized adhesions. Hence, intrahepatic recurrence in the left liver remnant after a previous open right hepatectomy may not necessarily be regarded as an absolute contraindication for the laparoscopic approach. Due to the small sample size in the present study, further studies are warranted to define the selection criteria for laparoscopic re-resection.

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more meticulous parenchymal transection. Because of our vast experience with CUSA in parenchymal transection over the past decades [17], it is conceivable for us to transfer the same operating technique to a newer approach in order to ensure a satisfactory postoperative outcome. In fact, further comparative analysis confirmed that the postoperative outcomes after open approach could be reproduced in the laparoscopic group but with less perioperative blood loss. Furthermore, the oncological outcomes in terms of R0 resection and prognosis appeared to be comparable between the two groups after a median follow-up of 25.6 months. In view of both favorable short- and long-term results, laparoscopic re-resection should be considered for recurrent HCC whenever it is technically feasible.

Fig. 2 Overall survival after re-resection: laparoscopic versus open approach

Conclusion Our study showed that laparoscopic re-resection for recurrent HCC was feasible with satisfactory postoperative and oncological outcomes, even in patients with previous major liver resections. Further studies are needed to elucidate its role in the management of recurrent HCC. Conflict of interest Funding

The authors have no conflicts of interest.

No additional funding was required.

References

Fig. 3 Disease-free survival after re-resection: laparoscopic versus open approach

Our recent study illustrated the potential benefit of laparoscopic liver resections over the conventional open approach in the management of primary HCC in terms of postoperative outcome [14]. However, data are scarce on the application of laparoscopic surgery to repeated liver resection [15]. Our preliminary experience suggested that laparoscopic re-resection is safe and feasible with early recovery of liver function, low postoperative morbidity, and limited hospital stay. Belli et al. [16] also reported their experience of laparoscopic re-resections in 12 patients with recurrent HCC. The relatively prolonged operating time (median 173 min) but lesser degree of blood loss (median 100 mL) in our patients as compared with their series could be attributed to the use of CUSA, which is associated with slower but

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Feasibility of laparoscopic re-resection for patients with recurrent hepatocellular carcinoma.

Repeated resection via an open approach is an effective treatment for post-operative recurrent hepatocellular carcinoma (HCC). However, there are limi...
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