Q4. Is Post-Operative pain less, and Quality of Life better,
after Laparoscopic Liver Resection (LLR)?
Nick O’Rourke
Mo Abu Hilal
Minoru Tanabe
Introduction
The main reason most surgeons perform laparoscopic surgery is to reduce postoperative pain and improve patient quality of life.
Intuitively, smaller incisions and less fixed abdominal wall retraction should cause
less pain, but as yet, there exists no level 1 evidence of the superiority of LLR. Many
observational trials and some case-matched comparative series do show reduced
pain with LLR, but significant heterogeneity exists not only in outcome measures,
but also in the wide variety of approaches to perioperative pain control making
systematic analysis impossible at this time. (Table 1).
Summary of reported methods used to measure post-operative pain in the
LLR literature:
Direct measures
1. Pain scores, such as Visual Analogue Scores (VAS) or various pain intensity
ratings at various intervals pre- and post- surgery. Clearly, these are only
available in a prospective fashion, although pain intensity scores are often part
of routine nursing observations.
Proxy measures
2. Analysis of analgesia requirement – e.g. Quantity or duration of narcotics
(narcotic equivalents),
3. Need for regional analgesia – e.g. Wound catheter, TAPP catheter or epidural.
Summary of reported methods used for HRQOL:
Multiple scoring systems are available and may be
1. Generic (eg SF-36)
2. Domain/disease specific (eg (FACT-Hep)
3. Cancer specific (eg FACT)
In the absence of good evidence in LLR, evidence from other laparoscopic
procedures has been examined:
The only “blinded” RCT for laparoscopic cholecystectomy did show a
reduction in pain scores after LC. (21) There is evidence from a Cochrane review
that laparoscopic colorectal resection is less painful than open. (22)
A large randomized trial on laparoscopic distal gastrectomy in Korea showed
reduced analgesic requirements in the lap group, as well as highly significant
improvements in quality of life scores out to 3 months. (23)
Can we infer similar benefits in LLR? Probably yes, to some degree, and in
essence cholecystectomy is a liver operation!
With liver resection however, laparoscopic surgery is even more difficult to
compare with open surgery, because of three liver resection variables:
1. Liver parenchyma can be normal, steatotic or cirrhotic.
2. Resection can be: minor, major (possibly extended),
3. LLR can be ‘pure’, ‘hand assist’, or hybrid.
This triple variety makes RCT’s more difficult, and further confounds the bias of
observational studies.
Literature Review, on LLR and Pain (Tables 1 and 2)
1. Laparoscopic hepatectomy (‘Pure’ and all types) vs. open: There are
many case matched series, which demonstrate reduced pain with LLR. (see
table). Most authors have analyzed dose or duration of narcotics, rather
than using pain scores. One of the best-matched studies is from Hong Kong
and demonstrated a highly significant pain difference in the median narcotic
dosage when comparing pure LLR vs. open (Lee 2007). Combining these
papers is not statistically reliable, because of different methodologies, but
one can say that 12 of the 15 published reports examining postoperative
pain claimed significantly reduced pain after LLR. Three showed no
difference.
2. Hand assist vs. open hepatectomy: A recent abstract from Noida, India,
claims less pain in lap hand assist donor right hepatectomies, compared to
an unspecified open donor group (2)
3. Lap Hybrid vs. open hepatectomy: There is a good series from Japan
looking at a consecutive series of left sided donor hepatectomy, with 31 lap
hybrid patients, compared to 79 previous open patients. There was no
difference in pain scores (VAS)(4)
Quality of Life Comparisons.
Very little data on formal quality of life analysis exists. A recent small case control
series, with poor matching, from Naples suggests significant improvement in SF36
scores, at 1 month (with conversions excluded) and 6 months, but no difference at
12 months. (1)
Using SF8 scores, surgeons from Noida (Delhi, India) demonstrated better quality
of life in patients undergoing hand assist donor right hepatectomy, compared to
those undergoing standard right hepatectomy. (2)
Over 80% of published comparative studies show reduced length of stay after LLR,
(Cherqui 2014, CQ1, Iwate.) and this may possibly be considered a surrogate marker
for Quality of Life.
The Norwegian RCT on lap vs open liver resection for up to 3 segments:
Unpublished data, (kindly provided by Bjorn Edwin and Asmund Fretland)
from the CoMeT trial from Norway, with 130 randomized patients ,does
demonstrate statistically significant improvement in “physical role” at both
4 weeks and 4 months.
Pain scores were not different at 4weeks or 4 months.
Conclusions
1. Pure laparoscopic liver resection seems to cause less pain than open liver
surgery. There may be little difference in pain following hybrid liver
operations. All centers should be encouraged to record pain scores
prospectively, in a standardized format.
2. Meaningful Quality of Life data is lacking. Scoring (SF36, FACT –G, FACT –
HEP,) should be considered for all benign cases. It may be more difficult in
malignancy with many patients undergoing adjuvant chemotherapy, or
further surgery.
TABLE 1. SUMMARY LIST OF STUDIES WITH PAIN CONTROL OUTCOMES
Case control/Cohort studies
Author/
Country/
Year
Unit/Code
Makki
India
2014
Makki_201
4
Study type
Population
Matching
$
Lap
(No. of
pt)
Open
(No. of
pt)
NOS scale#
Pain measure and
assessment
Outcome
Comments
Prospective
cohort study
HALS vs.
open live
donor R
hepatecto
my
Not Done
26
24
****/0/***
LAP
BETTER
QOL study
administered by
member of transplant
team –Risk of bias
No preoperative QOL
study for comparison
Slakey
USA
2013
LLM00055
Retrospective
Case control
Consecutive
series of
laparoscopic
resection
Benign and
malignant
liver lesions
Control
from same
time period
of study
1-9
Priority
indicatio
n and
anatomy
of lesions
45
(43 pure)
17
**/**/***
Mean morphine 1st 3
days requirement to
maintain VAS
<3(140.76 lap, 172.71
open) p=0.016
VAS for pain severity
lower POD4-10 with
lap, p=0.02
IV pain med>5d/
ND (0.17)
No pain score
measure
NO
DIFFEREN
CE
-Duration of study not
statedvolume of
centre
-No stats for
matching-size (6.4 vs.
10.5)/lesions/resectio
n
-Small numbers
Marubashi
Japan
2013
LLM00120
Prospective
consecutive
cohort series
Live lap
LDLT
donors left
sided grafts
Historical
open
controls
5 (type of
resection
)
31
79
**/0/***
40hr IV fentanyl +
analgesia till POD7
NO
DIFFEREN
CE
Different time period
of study groups
No matching
performed
SF36 not performed
on open group in
same series –
comparison to other
group? Validity
Schultz
Denmark
2013
LLM00302
Prospective
consecutive
cohort series
Liver
resection in
context of
ERAS
Not Done
13
87
(55 <3seg
minor)
***/0/**
Paracetamol/
Celecoxib/Gabapentin
+ epidural (open)
Nil diff on pain score
(Visual analog scale)
NO
DIFFEREN
CE
Nquyen
USA
2010
LLM00288
Retrospective
case control
(review paper
with local
CRC mets
and HCC
compared
separately
Not
stated
24(CRC)
17(HCC)
25(CRC)
20(HCC)
NA
Less epidural
placement for
postoperative pain
control (8.3% lap, 40%
LAP
BETTER
Selection bias
between groups
Treatment bias (no epi
for lap)
Crossover bias (lap>open? epidural)-not
analyzed as intention
to treat
Unusual to need ‘postop placement ‘ of
epidural, unless they
mean an epidural left
No pain score
measure
data)
Endo
Japan
2009
LLM00101
Retrospective
case control
Tsinberg
USA
2009
LLM00081
Retrospective
case control
Ito
France
2009
LLM00037
Retrospective
case control
(historical
control)
Carswell
UK
2009
LLM00018
Mixed pure
lap (56.1%)
hand assist
(37.3%)
hybrid
(3.5%)
robotic
(<0.1%)
LLS for HCC
open) p=0.01
in after surgery.
4,5,6,8
10
11
*/*/**
Total number of times
analgesics given.
Lap better
(p<0.05)
No pain score
measurement
LAP
BETTER
No standardization of
analgesics given/detail
of type of analgesics
Mixed
benign/
malignant
Some hand
ports
(unspecifie
d number)
All tumours
benign/mal
ignant
(56.1%
Hand
assisted)
1,4,5
31
43
***/0/**
IV narcotics
requirements (days)
Lap better <0.001
No pain score
measurement
LAP
BETTER
Not detailed type of
narcotics/oral
duration of meds
1-9
65
65
***/**/***
*
Time to oral analgesia
(days) 3 vs. 4
Lap better
<0.001
No pain score
measurement
LAP
BETTER
Assessment, selection
bias.
No documentation of
analgesia type,
epidural/IV analgesia
Retrospective
cohort study
LLS mixed
benign/
malignant
5
10
10
***/*/***
LAP
BETTER
Small series
Selection bias
No standardization of
opioid usage,
confounder of
epidural in open group
Saint Marc
Italy
2008
LLE00084
Retrospective
cohort study
Major
hepatecto
my only
All benign
5
6
6
**/*/**
Epidural use (9/10
open, 1/10 lap)
p=0.003
Median Opioid use
(2days lap, 5days
open) p=0.005
Lap better
No pain score
assessment
Lap better
Paracetamol/
Morphine (days)
(2.6 lap, 4.8 open)
No pain score
assessment
LAP
BETTER
Cai
China
2008
LLM00079
Retrospective
case control
Malignant
liver
tumours
1-9
31
31
*/**/*
LAP
BETTER
Lee
HK
2007
LLM00029
Retrospective
case control
1-9
25
25
***/**/*
Tang
HK
2005
Tang_2005
Retrospective
cohort study
Well
matched
series, pure
LLR vs.
open
LLS for RPC
(Hand
assist)
Analgesic requirement
(cases)
Lap better
0.03
No pain score
measurement
Median morphine
dosage
Lap better
<0.001
Limited details re:
open group for
matching
No analgesic regime?
Epidural
Opiate delivery not
clear
? Majority no
analgesia No
documentation of
analgesia
type/use/route/assess
ment
Very good matching.
ND
10
7
****/0/***
LAP
BETTER
Non matched
retrospective cohort
of lap (hand assisted)
vs. open (historic)
Mala
Norway
2002
Mala_2002
Retrospective
case control
CLR mets
Minor
resection
s, type of
resection
13(15
procedur
es)
14(14
procedur
es)
*/**/**
Fewer intramuscular
pethidine
injections(mg)/
less oral
dologesic(tab)
Lap better
0.002
No pain score
measurement
Post operative need
for opiates (days) 1(07) vs. 5(2-11)
Lap better
LAP
BETTER
Assessment, selection
bias. No
documentation of
analgesia type,
LAP
BETTER
1,2,3,4,7,
8,9
Farges
France
2002
LLM00042
Retrospective
case control
(2 years vs. 5
years open)
All benign
tumours
1,2,4,5
21
21
*/*/**
Open
(No. of
pt)
NA
NOS scale#
0.001
No pain score
measurement
Cumulative dose of
morphine/acetaminop
hen
Lap better
0.02 (sig for
morphine)
No pain score
measurement
epidural/IV analgesia
LAP
BETTER
Most benefit day 1
post op
Pain measure/
Outcome (p)
Outcome
Comments
NA
Duration of IV
narcotics favours lap >2.15 days shorter
(p<0.001)
LAP
BETTER
3 studies included
Heterogeneity not
significant
Review papers addressing pain control
Author/Year
Unit/Code
Study type
Population
Matching
$
Croome
USA
2010
Croome_20
10
Metaanalysis
Benign and
malignant
NA
Lap
(No. of
pt)
NA
Reddy
USA
2011,
LLM00307
Nguyen
USA
2010
LLM00288
Good
review.
Plus data
from
Pittsburgh.
NA
NA
NA
NA
NA
Significantly better lap
cf. days of narcotic
pain medications
needed and total
amount of pain meds
required
LAP
BETTER
Systematic review
Pulitano
Italy
2008
LLE00077
Review
NA
NA
NA
NA
NA
Less pain with lap
LAP
BETTER
Used papers (Mala,
Farges) for data on
pain
TABLE 2. SUMMARY LIST OF STUDIES WITH QOL OUTCOMES
Case control/Cohort studies
Author/Year
Unit/Code
Study type
Population
Matching Lap
$
(No. of pt)
Open
(No. of pt)
NOS scale#
Giuliani
Italy
2014
Guilaini_20
14
Retrospectiv
e cohort
study
All benign
Only 2
major
(RH/LLS+
IVb) for lap
Included
non
resectional
procedures
(fenestratio
n/pericyste
ctomy)
ND
29
46
**/0/**
Makki
India
2014
Makki_201
4
Prospective
cohort study
HALS vs.
open live
donor R
hepatecto
my
ND
26
24
Marubashi
Japan
2013
LLM00120
Prospective
consecutive
cohort series
Live lap
LDLT
donors left
sided grafts
Historical
open
controls
5 (type
31
resection
)
79
QOL measure and
results
Outcome
Comments
Better at 6 (PF, BP)
and 12 (PF) months.
Better at 1(BP, PF)
month, (When
conversions added to
open group)
LAP
BETTER
ITT analysis.
Much higher
percentage of majors
done open (48%) vs.
lap (7%)
High dropout rate
(15%) for open group
esp. majors vs. lap
(3%).
Classification for lap
major’s not standard
definition.
****/0/***
SF-8 used.
At 4 weeks- better
QOL mental
component with lap
(p<0.01) but physical
component no diff.
No diff at 6 months
LAP
BETTER
QOL study
administered by
member of transplant
team –response bias
No preoperative QOL
study for comparison
**/0/***
Claim better SF36
against other series
(diff population)
LAP
BETTER
Different time period
of study groups
No matching
performed
SF36 not performed
on open group in
same series –
comparison to other
group? Validity
Table Legend: # Based on Newcastle-Ottawa Scale with maximum of **** for selection, ** for
comparability and **** for outcome
$ Matching/comparable factors are (1) age, (2) sex, (3) number of benign or malignant tumours, (4)
mean size of tumours, (5) location of resection, (6) cirrhosis, (7) liver metastasis, (8) Primary
malignant tumour, and (9) neoplasm histological finding
References for articles
1. Giuliani et al. Laparoscopic vs. open surgery for treating benign liver lesions:
assessing quality of life in the first year after surgery. Updates Surg. 2014
Jun; 66(2): 127-33
2. Makki et al. Laparoscopic assisted versus conventional (open) donor
hepatectomy for live donors: When you know better, you do better. Liver
Transpl 2014 Jun 25. Doi:10.1002/lt.23940 (Epub ahead of print)
3. Slakey et al. Complications of liver resection: laparoscopic versus open
procedures. JSLS (2013) 17:46-55.
4. Marubashi et al. Laparoscopy-Assisted Hybrid Left-Side Donor
Hepatectomy. World J Surg (2013) 37:2202-2210.
5. Schultz et al. Evaluation of a fast-track programme for patients undergoing
liver resection. BJS 2013; 100:138-143
6. Nguyen et al. Comparative benefits of Laparoscopic vs. Open Hepatic
Resection. Arch Surg 2011; 146(3): 348-3
7. Endo et al. A comparative study of Long-term Outcomes After Laparoscopyassisted and Open Left Lateral Hepatectomy for Hepatocellular Carcinoma.
Surg Laparosc Endosc Percutan Tech 2009;19: e171-174
8. Tsinberg et al. Comparison of laparoscopic versus open liver tumor
resection: a case-controlled study. Surg Endosc 2009; 23:847-853
9. Ito et al. Laparoscopic versus open liver resection: A Matched-Pair Case
Control Study. Gastrointest Surg 2009; 13: 2276-2283
10. Carswell et al. Laparoscopic versus open left lateral segmentectomy. BMC
Surgery 2009; 9:14
11. Saint Marc et al. Early experience with laparoscopic major liver resections.
Surg Laparosc Endosc Percutan Tech 2008; 18:551-555
12. Cai et al. Clinical study of laparoscopic versus open hepatectomy for
malignant liver tumors. Surg Endosc 2008; 22:2350-2356
13. Lee et al. Laparoscopic versus open hepatectomy for liver tumours: a case
control study. Hong Kong Med J 2007; 13:442-8
14. Tang et al. Laparoscopy vs. open left lateral segmentectomy for recurrent
pyogenic cholangitis. Surg Endosc 2005; 19:1232-1236
15. Mala et al. A Comparative study of the short-term outcomes following open
and laparoscopic liver resection for colorectal metastases. Surg Endosc
2002; 16:1059-1063
16. Farges et al. Prospective assessment of the safety and benefit of
laparoscopic liver resections. J Hepatobiliary Pancreat Surg 2002; 9:242248
17. Kaneko et al. Laparoscopic liver resection of hepatocellular carcinoma. The
American Journal of Surgery 2005; 189: 190-194
18. Reddy et al. Laparoscopic liver resection. World J Surg 2011; 35: 1478-1486
19. Pulitano et al. The current role of laparoscopic liver resection for the
treatment of liver tumors. Nat Clin Pract Gastroenterol Hepatol 2008 Nov;
5(11): 648-54
20. Croome et al. Laparoscopic vs. Open Hepatic Resection for Benign and
Malignant tumors. Arch Surg 2010; 145(11):1109-1118.
21. Squirrell et al. A randomized, prospective, blinded comparison of
postoperative pain, metabolic response, and perceived health after
laparoscopic and small incision cholecystectomy. Surgery 1998 May;
123(5): 485-95
22. Schwenk et al. Short-term benefits for laparoscopic colorectal resection.
Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003145
23. Kim et al. Improved quality of life outcomes after laparoscopy-assisted distal
gastrectomy for early gastric cancer: results of a prospective randomized clinical
trial. Ann Surg. 2008 Nov; 248(5):721-7