Q4. Is Post-Operative Pain Less, and Quality of Life Better, After Laparoscopic Liver

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 post-operative 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

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

Analysis of analgesia requirement – e.g. Quantity or duration of narcotics (narcotic equivalents),

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

Generic (eg SF-36)
Domain/disease specific (eg (FACT-Hep)
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 LLRand Pain(Tables 1 and 2)

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 dosagewhen 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.

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)

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 AsmundFretland) from the CoMeT trial from Norway, with 130 randomized patients ,does demonstrate statistically significant improvement in “physical role” at both 4 weeks and 4months.

Pain scores were not different at 4weeks or 4 months.

Conclusions

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.

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 / Study type / Population / Matching$ / Lap
(No. ofpt) / Open
(No. ofpt) / NOS scale# / Pain measure and assessment / Outcome / Comments
Makki
India
2014
Makki_2014 / Prospective cohort study / HALS vs. open live donor R hepatectomy / Not Done / 26 / 24 / ****/0/*** / 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 / 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 indication and anatomy of lesions / 45
(43 pure) / 17 / **/**/*** / IV pain med>5d/
ND (0.17)
No pain score measure / NO DIFFERENCE / -Duration of study not statedvolume of centre
-No stats for matching-size (6.4 vs. 10.5)/lesions/resection
-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 pain score measure / NO DIFFERENCE / 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 DIFFERENCE / Selection bias between groups
Treatment bias (no epi for lap)
Crossover bias (lap->open? epidural)-not analyzed as intention to treat
Nquyen
USA
2010
LLM00288 / Retrospective case control
(review paper with local data) / CRC mets and HCC compared separately
Mixed pure lap (56.1%) hand assist (37.3%) hybrid(3.5%) robotic (<0.1%) / Not stated / 24(CRC)
17(HCC) / 25(CRC)
20(HCC) / NA / Less epidural placement for postoperative pain control (8.3% lap, 40% open) p=0.01 / LAP BETTER / Unusual to need ‘post-op placement ‘ of epidural, unless they mean an epidural left in after surgery.
Endo
Japan
2009
LLM00101 / Retrospective case control / LLS for HCC / 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
Tsinberg
USA
2009
LLM00081 / Retrospective case control / Mixed benign/
malignant
Some hand ports (unspecified number) / 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
Ito
France
2009
LLM00037 / Retrospective case control (historical control) / All tumours benign/malignant
(56.1% Hand assisted) / 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
Carswell
UK
2009
LLM00018 / Retrospective cohort study / LLS mixed benign/
malignant / 5 / 10 / 10 / ***/*/*** / 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 / Small series
Selection bias
No standardization of opioid usage, confounder of epidural in open group
Saint Marc Italy
2008
LLE00084 / Retrospective cohort study / Major hepatectomy only
All benign / 5 / 6 / 6 / **/*/** / Lap better
Paracetamol/
Morphine (days)
(2.6 lap, 4.8 open)
No pain score assessment / LAP BETTER / Limited details re: open group for matching
No analgesic regime? Epidural
Opiate delivery not clear
Cai
China
2008
LLM00079 / Retrospective case control / Malignant liver tumours / 1-9 / 31 / 31 / */**/* / Analgesic requirement (cases)
Lap better
0.03
No pain score measurement / LAP BETTER / ? Majority no analgesia No documentation of analgesia type/use/route/assessment
Lee
HK
2007
LLM00029 / Retrospective case control / Well matched series, pure LLR vs. open / 1-9 / 25 / 25 / ***/**/* / Median morphine dosage
Lap better
<0.001 / LAP BETTER / Very good matching.
Tang
HK
2005
Tang_2005 / Retrospective cohort study / LLS for RPC
(Hand assist) / ND / 10 / 7 / ****/0/*** / Fewer intramuscular pethidineinjections(mg)/
less oral dologesic(tab)
Lap better
0.002
No pain score measurement / LAP BETTER / Non matched retrospective cohort of lap (hand assisted) vs. open (historic)
Mala
Norway
2002
Mala_2002 / Retrospective case control / CLR mets / Minor resections, type of resection
1,2,3,4,7,8,9 / 13(15 procedures) / 14(14 procedures) / */**/** / Post operative need for opiates (days) 1(0-7) vs. 5(2-11)
Lap better
0.001
No pain score measurement / LAP BETTER / Assessment, selection bias. No documentation of analgesia type, epidural/IV analgesia
Farges
France
2002
LLM00042 / Retrospective case control (2 years vs. 5 years open) / All benign tumours / 1,2,4,5 / 21 / 21 / */*/** / Cumulative dose of morphine/acetaminophen
Lap better
0.02 (sig for morphine)
No pain score measurement / LAP BETTER / Most benefit day 1 post op
Review papers addressing pain control
Author/Year
Unit/Code / Study type / Population / Matching$ / Lap
(No. ofpt) / Open
(No. ofpt) / NOS scale# / Pain measure/
Outcome (p) / Outcome / Comments
Croome
USA
2010
Croome_2010 / Meta-analysis / Benign and malignant / NA / NA / NA / NA / Duration of IV narcotics favours lap ->2.15 days shorter (p<0.001) / LAP BETTER / 3 studies included
Heterogeneity not significant
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/YearUnit/Code / Study type / Population / Matching$ / Lap
(No. ofpt) / Open
(No. ofpt) / NOS scale# / QOL measure and results / Outcome / Comments
Giuliani
Italy
2014
Guilaini_2014 / Retrospective cohort study / All benign
Only 2 major (RH/LLS+
IVb) for lap
Included non resectional procedures (fenestration/pericystectomy) / ND / 29 / 46 / **/0/** / 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.
Makki
India
2014
Makki_2014 / Prospective cohort study / HALS vs. open live donor R hepatectomy / ND / 26 / 24 / ****/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
Marubashi
Japan
2013
LLM00120 / Prospective consecutive cohort series / Live lap LDLT donors left sided grafts
Historical open controls / 5 (type resection) / 31 / 79 / **/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

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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)
Slakey et al. Complications of liver resection: laparoscopic versus open procedures. JSLS (2013) 17:46-55.
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