Laparoscopic versus Open Non-anatomical Hepatectomy for Hepatocelluar Carcinoma in Cirrhotic Liver

Document Type : Original Article

Authors

1 General Surgery Department, Faculty of Medicine, Ain Shams University. Egypt.

2 Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Egypt.

Abstract

Background: Although the use of laparoscopy has gradually gained favor, the short-term benefits generally observed with laparoscopy applied to patients undergoing partial hepatic resection remains unclear. The aim of the present study was to report and compare the results of patients undergoing laparoscopic hepatectomy (LH) and open hepatectomy (OH) in short term follow up.
Patients and methods: This is a controlled randomized prospective study conducted in Ain Shams University Hospitals between December 2012 and April 2015 comparing laparoscopic non-anatomic hepatectomy (15 patients) and open non-anatomic hepatectomy (15 patients) in the management of HCC in cirrhotic patients.
Results: There were no significant differences between both groups regarding operative time (145 ±43 min Vs 152 ±49.92 min P =0.679), blood loss (376 ±250ml Vs 526 ±307 ml P =0.156). Overall complication rate (46.7% Vs 53.3% P =0.715), post-operative ascitis (P =0.156) and overall thirty day mortality (0% Vs 6.7% P =0.31). Safety margin was adequate in both groups. Hospital stay was significantly lower in the group of LH (9.8 ±3.76 days) than in the group of OH (15 ± 4.76 days) (P = 0.001).
Conclusion: Laparoscopic non-anatomical hepatectomy for HCC in cirrhotic liver is equally safe and feasible in segments II to VI.

Keywords


 

Laparoscopic versus Open Non-anatomical Hepatectomy for

Hepatocelluar Carcinoma in Cirrhotic Liver

 

 

H. Said,1 MD, Mohamed Elnagar,1 MD, MRCS; Ahmed Helal,2 MD.

 

 

1) General Surgery Department, Faculty of Medicine, Ain Shams University.

Egypt.

2) Department of Tropical Medicine, Faculty of Medicine, Ain Shams

University, Egypt.

 

 

Background: Although the use of laparoscopy has gradually gained favor, the short-term benefits generally observed with laparoscopy applied to patients undergoing partial hepatic resection remains unclear. The aim of the present study was to report and compare the results of patients undergoing laparoscopic hepatectomy (LH) and open hepatectomy (OH) in short term follow up.

Patients and methods: This is a controlled randomized prospective study conducted in Ain Shams University Hospitals between December 2012 and April 2015 comparing laparoscopic non-anatomic hepatectomy (15 patients) and open non-anatomic hepatectomy (15 patients) in the management of HCC in cirrhotic patients.

Results: There were no significant differences between both groups regarding operative time (145 ±43 min Vs 152 ±49.92 min P =0.679), blood loss (376 ±250ml Vs 526 ±307 ml P =0.156). Overall complication rate (46.7% Vs 53.3% P =0.715), post-operative ascitis (P =0.156) and overall thirty day mortality (0% Vs 6.7% P =0.31). Safety margin was adequate in both groups. Hospital stay was significantly lower in the group of LH (9.8 ±3.76 days) than in the group of OH (15 ± 4.76 days) (P = 0.001).

Conclusion: Laparoscopic non-anatomical hepatectomy for HCC in cirrhotic liver is equally safe and feasible in segments II to VI.

Key words: Laparoscopic hepatectomy, open non-anatomical hepatectomy, hepatocelluar carcinoma, cirrhotic liver.

 

 

 

 

 

 

Introduction:

Hepatic surgery is one of the most challenging and complex procedures requiring considerable expertise. Laparoscopic hepatic surgery requires additional advanced skills.1

Laparoscopic    liver    resection    was    first performed in the 1990s, and the first formal anatomical resection in 1996.2 Despite the technical difficulties, more centers have been using laparoscopy in hepatic surgery in the last decade.

The  Louisville  Statement  in  2008 suggests  that  laparoscopic  hepatectomy (LH) has become a widely accepted surgical procedure  for  liver  lesions.3  Studies  from


different medical centers have confirmed the safety and feasibility of open hepatectomy (OH)  for  patients  with  an  acceptably  low complication rate and satisfying oncological outcomes.4 Although the use of laparoscopy has  gradually  gained  favor,  the short-term benefits generally observed with laparoscopy applied to patients undergoing partial hepatic resection   remains   unclear.5   Advances   in laparoscopic          techniques       and      instruments have rendered laparoscopic procedures more safe and feasible in surgical operations with less  blood  loss,  shorter  hospital  stay  and without  compromised  complication  rate  or oncological outcomes compared with open

 

 

 

surgery.6

The  aim  of  the  present  study  was  to report and compare the results of patients undergoing laparoscopic hepatectomy (LH) and open hepatectomy (OH) in short term follow up.

 

Aim of this study:

Was to compare between laparoscopic hepatectomy (LH) and open hepatectomy (OH) in short term follow up.

 

Patients and methods:

This is a controlled randomized prospective study conducted in Ain Shams University Hospitals between December 2012 and April

2015. Thirty patients were included in this study and were divided into two groups (LH and OH); fifteen patients in each group.

Inclusion criteria for patients undergoing either LH or OH with

•      Hepatocellular carcinoma.

•      Patients with liver cirrhosis.

•      Child-Pugh classification A.

•      Solitary HCC.

•      Tumor size more than 3 cm.

•      Tumor   size   less   than   3   cm   if sub-capsular.

•      Segment II, III, IVb, V and VI for laparoscopic group.

•       Non-anatomical resection. Exclusion criteria:

•      Child-Pugh classification B or C.

•      Previous treatment of HCC.

•      Tumor less than 3 cm central.

•      Satellite nodules.

•      Segmental portal vein thrombosis.

•       Previous upper abdominal surgery. Hepatocellular carcinoma was diagnosed

with  typical  criteria  by  the  triphasic  CT with  or  without  AFP  elevation.  Triphasic CT  determined  number,  site,  size  of  the HCC, major vascular invasion, lymph node metastasis and ascitis.

Bone scan and chest CT in some patients

with poor prognostic criteria like AFP > 400.

All patients were evaluated by liver function test, coagulation profile for calculation of Child-Pugh classification. Routine  preoperative  assessment  complete


blood count, kidney function as well as routine cardio-respiratory evaluation were done.

 

Surgical technique:

Laparoscopic Hepatectomy (LH):All operations were performed under general anesthesia. Each patient was placed in supine position, legs apart and tilted 30° to the left or right according to the lesion location. The primary surgeon stood between the patient’s legs with one assistant on either side. Left semi-decubitus  position  was  used  if  the lesion was in segment VI with the surgeons stood on the left side of the patient. Three

10–12 mm trocars were inserted routine and the  forth  5  mm  was  inserted  on  demand. First  one  was  placed  supra-umbilical  for

30o scope, other trocars sites were planned case by case according to the site of the lesion. Start with abdominal exploration. Limited liver mobilization according to the need. Liver parenchymal transection was performed using a combination of harmonic scalpel and bipolar forceps. Small vessels were coagulated directly and large vessels (diameter ≥3 mm) were occluded using titanium clip or Hem-o-lok clamping. Major vessels were divided by application of vascular stapling devices (once for lesion in segment II and III). During liver transection, the intravenous fluid was carefully controlled. Central venous pressure was maintained at a low level (<5 mm Hg). Laparoscopic control of bleeding included a transient increase in pneumo-peritoneum pressure to 16 mmHg. The resected specimens were placed in a plastic retrieval bag and removed through a widening in port site. Abdominal drainage tube was usually inserted Figure (1).

Open Hepatectomy (OH): All operations were performed under general anesthesia. The patients were placed in the supine position. The liver resections were performed through a hooky stick incision. Start with exploration of  the  abdominal  cavity  and  mobilization of the liver. The pedicle was prepared to enable performance of the Pringle maneuver when    needed.    Parenchymal    transection was  achieved  with  the  harmonic  scalpel.

 

 

 

 

 

 

Figure (1): Laparoscopic hepatectomy: marking of tumor, excision of the tumor, homeostasis, liver after excision.

 

 

 

Figure (2): Open hepatectomy.

 

 

 

Control  of  minor  bleeding  was  obtained with monopolar electrocoagulation. Clips or nonabsorbale sutures were used for ligation of major vessels. Abdominal drainage tube was usually inserted Figure (2).

All patients were transferred to the intensive care unit (ICU) after the operation and  then  transferred  to  the  general  ward when the condition became stable. Follow up laboratory daily and Doppler ultrasound twice weekly.

Comparison between both groups regarding operative  time,  intra-operative  blood  loss,


blood transfusion, safety margin, hospital stay, post-operative ascitis, post-operative complications and mortality. Postoperative complications     were    stratified   according to the Clavien-Dindo classification,7 and complications of grade III or greater were considered severe Table (1).

Statistical   analysis:   Analysis   of   data was done by IBM computer using SPSS (statistical program for social science version

16) as follows: description of quantitative variables as mean, SD and range, description of   qualitative   variables   as   number   and

 

 

Table (1): The Clavien-Dindo Classification of Surgical Complications.

 

Grades

 

Definition

 

 

 

Grade  I:

Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions.

 

 

Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgesics, diuretics and electrolytes and physiotherapy. This grade also includes wound infections opened at the bedside.

Grade  II:

Requiring pharmacological treatment with drugs other than such allowed for grade I complications.

Blood transfusion and total parenteral nutrition are also included.

Grade  III:

Requiring surgical, endoscopic or radiological intervention.

Grade

III-a:

Intervention not under general anesthesia.

Grade

III-b:

Intervention under general anesthesia.

Grade IV:

Life-threatening complications (including CNS complications)‡ requiring IC/ ICU-management.

Grade

IV-a:

Single organ dysfunction (including dialysis).

Grade

IV-b:

Multi-organ dysfunction.

 

Grade V:

Death of a patient.

 

Suffix ‹d›:

If the patient suffers from a complication at the time of discharge,  the suffix

“d” (for ‘disability’) is added to the respective grade of complication. This label indicates the need for a follow-up to fully evaluate the complication.

‡ brain hemorrhage, ischemic stroke, subarachnoidal bleeding,but excluding transient ischemic attacks (TIA);IC:

Intermediate care; ICU: Intensive care unit. Dindo D., Demartines N., Clavien P.A.; Ann Surg. 2004; 244:

931–937.

 

 

Table (2) Demographic data:

 

 

Group A: Laparoscopic hepatectomy

Group B: Open hepatectomy

 

P value

 

Sex (number /frequency)

Male 12 (80%) Female 3 (20%)

Male 11 (73.3%) Female 4 (26.7%)

 

0.66

Age  (mean ±SD)

52.66 ± 6.52

58.6 ± 7.61

0.68

 

HCV (number /frequency)

Yes 14(93.3 %) No   1 (6.7%)

Yes 13 (86.7 %) No  2 (13.3%)

 

0.14

 

HBV (number /frequency)

Yes 2 (13.3 %) No 13 (86.7%)

Yes 1 (93.3 %) No   14 (6.7%)

 

0.54

PORTAL HYPERTENSION (number /frequency)

Yes 3 (20 %) No   12 (80%)

Yes 3 (20 %) No   12 (80%)

 

1

AFP (mean ±SD)

270.93 ± 617.1

184.66 ± 234.44

0.617

Tumor size (mean ±SD)

4.3 ± 1.6

5.7 ± 1.3

0.179

 

 

Table (3) Comparison between I-O data, post-operative data and safety margin:

 

 

Group A

Laparoscopic hepatectomy

Group B

Open hepatectomy

P value

Operative time (mean ±SD)

145.53 ± 43.34

152 ± 49.92

0.679

I-O blood loss (mean ±SD)

376 ± 256.92

526.66 ± 307.56

0.156

Drain amount (mean ±SD)

283.33 ± 180.93

396.67 ± 222.37

0.156

Postoperative complication (number

/frequency)

Yes 7 (46.7%) No 8 (53.3%)

Yes 8 (53.3%) No 7 (46.7%)

0.715

Complication grade  (median/range)

1 (0 – 3)

2 (1 – 5)

0.704

Hospital stay (mean ±SD)

9.8 ± 3.76

15 ± 4.76

0.001

Mortality (number /frequency)

No 15 (100%)

No 14(93.3) Yes 1 (6.7%)

0.31

Safety margin (number /frequency)

Yes 13 (86.7%) No 2 (13.3%)

Yes 14 (93.3%) No 1(6.7%)

0.543

 

 

 

percentage, Chi-square test was used to compare matched pairs before and after intervention. P value >0.05 was considered insignificant, P<0.05 was considered significant, P<0.001 was considered highly significant.

 

Results:

Thirty  patients  were  included  in  this study divided into 2 groups. Group (A), fifteen patients undergoing laparoscopic hepatectomy and group (B), fifteen patients undergoing open hepatectomy. Demographic data of both groups were comparable Table (2). In the LH group males to females ratio was (12:3), while in OH group males to females ratio was (11:4). Mean age in group A was

52.6±6 and in group B was 58.6±7. Thirteen patients in group A had HCV, one patient had HBV and one patient had HCV and HBV. In group B thirteen patients had HCV, one had HBV and one had cryptogenic cirrhosis. All patients in both groups were CTP A and 20% of both group had manifestation of portal hypertension  (spleenomegally  and  platelet

<100).

Tumor data regarding size, site and Alpha Feto-protein   were   comparable.   In   group A tumor  size  ranged  from  2–7  cm  (mean

4.3±1.6), AFP ranged  from  8–2400  (mean

270±617) and commonest tumor sites were segment IVb (26.7%) followed by segment


III, V and VI (20% for each). In group B tumor size  ranged  from  3–9  cm  (mean  5.7±1.3), AFP ranged from 14–900 (mean 184±231) and  commonest  tumor  sites  were  segment IVa, V and VII (20% for each) followed by segment VI (13.3%).

Operative  and  postoperative  outcomes: Intra-operative   data,   post-operative   data and adequate safety margin were all non significant differences between both groups except for hospital stay. Mean operative time was 145±43 min. in group A versus 152±49.92 min in group B (P =0.679). In spite of lower blood loss in group A (376±250) than in group B (526±307) but it was statistically non significant (P =0.156).

Conversion to open occurred in two cases, first was for apparent bleeding and second was for colonic injury at hepatic flexure during mobilization of the right lobe. Primary repair was done with smooth post-operative course.

Overall morbidity was (46.7%) for LH versus (53.3%) for OH; P =0.715) and severity of complications were not different between  the  two  groups.  Specifically, the rate of minor morbidity (Clavien- Dindo grades I-II) was similar (33.3% for LH; Vs

40% for OH P =.67), as was the rate of major morbidity       (Clavien-Dindo   grades   III-V) (13.3% in each group; P >.99). There was no  significant  difference  regarding  ascitis

 

 

 

between  both  groups  (P  =0.156).  Overall

thirty day mortality was (0%for LH versus

6.7% for OH; P =0.31). Safety margin was

adequate in both groups.

Length of hospital stay was significantly lower in group A (9.8±3.76 days) than in group B (15±4.76 days) (P =0.001).

 

Discussion:

Although recent studies suggested the feasibility of LH, this procedure remains challenging and demands both laparoscopic and hepatobiliary surgery expertise especially in cirrhotic patients.8 One of the initial barriers to perform laparoscopic partial hepatic resection was concerned with the safety of laparoscopic hemostatic technique. Despite the technical difficulties, more centers have been using laparoscopy in hepatic surgery in the last decade.9

Liver resection has been associated with increased blood loss and blood product transfusion when compared with other surgical procedures leading to increase risk of short-term or long-term morbidity and mortality.10  Several factors may contribute to the decreased blood loss in laparoscopic hepatectomy. The application of laparoscopy allows more meticulous hemostasis, which offered the surgeons a very clear view with magnification. The raised intra-abdominal pressure from pneumo-peritoneum minimizes oozing of blood during the operation.11  In this study, blood loss decreased in LH group but not statistically significant ( LH vs. OH was 356 Vs 526 ml with P 0.156). This finding may be due to early experience with laparoscopic hepatectomy or unlimited tumor size, as we had four cases with tumor >5cm and all of our patients had liver cirrhosis.

The largest meta-analysis up to date on the subject of LH versus OH reported a 59.9% lower  risk  of  postoperative  complications after LH. However, the decrease in complications was not universally observed among  the  included  studies.  Only  8  of those   26   studies   even   reported   a   liver- specific complication (bile leakage) and no significant difference was noted.12 However, in our study with regard to the short-term


outcome of overall complications, there was no difference between the groups with regard to the significant complication rate (46.7% Vs 53.3%: P =0.715). Defined as Clavien- Dindo (CD) classification, the rate was for CDI & II ( 33% vs. 40%) for LH versus OH and for CD III–V was the same (13.3%) for both.  Respiratory  complications  were  the most common complication. Bile leakage happened only in OH. Regarding mortality within thirty days, it occurred in one patient in OH group.

Laparoscopic   procedures   may   in   fact also provide oncological benefits compared to open approach. In a recent study by Shi and colleagues, it was shown that a resection margin of 2 cm provided better long-term outcomes for HCC compared to the traditional

1 cm. The results of this meta-analysis had shown that surgeons performing laparoscopic procedures returned wider histological tumour margins following resection when compared to       the   open   approach.   High   definition magnification may provide easier assessment of the affected tissue and aid the surgeon to resect a tumour-free wide margin.13 In our study adequate safety margin (>1 cm) was achieved in both groups.

Decreased hospital stay has been shown to be a benefit of LH. The benefit is presumed to be related to the observed decrease in duration of intravenous narcotics and the time to oral intake.14 We observed a significant decrease in hospital stay between both group (mean hospital stay was 9.8±3.76 and 15±4.76 for LH and OH groups respectively P =0.001). Patients underwent laparoscopic hepatectomy showed better organ function reserve and faster  postoperative  rehabilitation  in  terms of ICU stay, first mobilization out of bed, starting oral intake and laboratory test results.

 

Conclusion:

Laparoscopic non-anatomical hepatectomy for HCC in cirrhotic liver is equally safe and feasible in segments II to VI.

 

Reference:

1-    Nguyen KT, Gamblin TC, Geller DA: World review of laparoscopic liver resection-2804

 

 

 

patients. Ann Surg 2009; 250: 831–841.

2-   Azagra JS, Goergen M, Gilbart E, Jacobs D: Laparoscopic anatomical (hepatic) left lateral segmentectomy: Technical aspects. Surg Endosc 1996; 10(7): 758–761.

3-   Buell JF, Cherqui D, Geller DA, O’Rourke N, et al: The international position on laparoscopic liver surgery. Ann Surg 2009;

250(5): 825–830.

4-   Adam R, Frilling A, Elias D, et al: Liver resection of colorectal metastases in elderly patients. Br J Surg 2010; 97: 366–376.

5-    Jensen  EH,  Vickers  SM:  The  maximally invasive hepatobiliary surgeon: A dying breed. Arch Surg 2010; 145(11): 1118.

6-   Afaneh C, Kluger MD: Laparoscopic liver resection: Lessons at the end of the second decade. Semin Liver Dis 2013; 33: 226–235.

7-   Dindo   D,   Demartines   N,   Clavien   PA: Classification of surgical complications: A new proposal with evaluation in a cohort of

6336 patients and results of a survey. Ann

Surg 2004; 240(2): 205–213.

8-   Dagher I, Di Giuro G, Dubrez J, Lainas P, Smadja C, Franco D: Laparoscopic versus open right hepatectomy: A comparative study. Am J Surg 2009; 198: 173–177.

9-   Ito  K,  Ito  H, Are  C,  et  al:  Laparoscopic

 

versus open liver resection: A matched-pair case control study. J Gastrointest Surg 2009;

13(12): 2276–2283.

10- Aramaki O, Takayama T, Higaki T, et al: Decreased blood loss reduces postoperative complications in resection for hepatocellular carcinoma.  J  Hepatobiliary  Pancreat  Sci

2014; 21: 85–91.

11-  Inoue Y, Hayashi M, Tanaka R, Komeda K, Hirokawa F, Uchiyama K: Short-term results of laparoscopic versus open liver resection for liver metastasis from colorectal cancer: A comparative study. Am Surg 2013; 79(5):

495–501.

12- Croome KP, Yamashita MH: Laparoscopic versus open hepatic resection for benign and malignant tumors: An updated meta-analysis. Arch Surg 2010; 145(11): 1109–1118.

13-  Twaij A, Pucher PH, Sodergren MH, Gall T, Darzi A, Jiao LR: Laparoscopic versus open approach to resection of hepatocellular carcinoma in patients with known cirrhosis: Systematic review and meta-analysis: World J Gastroenterol 2014; 20(25): 8274–8281.

14-  Olsén MF, Wennberg E: Fast-track concepts in major open upper abdominal and thoraco- abdominal surgery: A Review World J Surg

2011; 35(12): 2586–2593.