A randomised controlled trial of optimised surgical recovery after left lateral hepatic sectionectomy: open versus laparoscopic surgery within an enhanced recovery programme.

Liver resection for colorectal metastasis is the only curative therapy and has
become the standard of care in appropriately staged patients, offering 5-year
survival rates of approximately 35-40%. Also for symptomatic benign lesions,
liver resection is a widely accepted treatment. Recent developments in liver
surgery include the introduction of laparoscopic surgery and enhanced recovery
programmes, which focus on optimalisation of postoperative recovery and/or
shorter hospital length of stay. Laparoscopic liver resection was first
described in 1995. Over the years laparoscopic liver resection has gained wide
acceptance for various liver resection procedures and a lot of effort has been
made to make this procedure safe and effective. Recently, various retrospective
case series and reviews comparing open with laparoscopic liver resection
indicate that laparoscopic liver resection can be applied safely for both
malignant and benign diseases. Several other case series reported that
laparoscopic liver resection was associated with shorter length of hospital
stay, less postoperative pain and earlier recovery. Stoot et al. found in a
retrospective study that hospital length of stay could be reduced with 3 days
in patients undergoing a left lateral hepatic sectionectomy (from 10 tot 7)
comparing to patients undergoing a open left lateral hepatic sectionectomy.
Furthermore, no evidence of a compromised oncological clearance in
laparoscopic liver resection has been found6. However, the type of
surgery/procedure itself is not the only variable that influences recovery and
hospital length of stay. Regarding postoperative care, enthusiasm was raised
for the so-called ERAS®-programme (enhanced recovery after surgery). This
multimodal program involves optimalisation of several aspects of the
perioperative management of patients undergoing major abdominal surgery. In
patients undergoing colectomy, the ERAS® programme enabled earlier recovery
and consequently shorter length of hospital stay. Also reduction of
postoperative morbidity in patients undergoing intestinal resection was
reported. These results stimulated liver surgeons of the ERAS® group
(Maastricht, Edinburgh and Tromso) to set up an ERAS-programme for every
patient undergoing open liver resection. Van Dam et al. found a significantly
accelerated recovery after open liver resection when patients were managed
within a multimodal ERAS protocol. Median hospital length of stay was reduced
from 8 to 6 days (25%). Also, the data suggested that a further reduction of
stay should be possible since there was a delay between recovery and discharge
of the patients. Maessen et al. reported a median delay of 2 days after
patients were functionally recovered. Regarding the results of previous,
non-randomised studies and case series, it seems that laparoscopic left lateral
liver sectionectomy is associated with shorter hospital length of stay, less
post-operative pain, better quality of life and a faster recovery. In most
trials aiming at a reduction of hospital length of stay, surgery and/or
perioperative management are not standardised. In addition, the added value of
laparoscopy compared to open liver surgery in left lateral liver sectionectomy
within an ERAS programme in terms of functional recovery, hospital length of
stay and postoperative morbidity and mortality has never been studied in a
randomised controlled setting. Therefore, this is the subject of the present
study proposal.

The ORANGE-II trial is a randomised controlled trial that will provide evidence
on the merits of laparoscopic surgery in patients undergoing a left lateral
hepatic sectionectomy and participating in an enhanced recovery programme.

The ORANGE-II trial is a prospective superiority study with an experimental
design, that produces two double blinded randomized controlled arms and a
prospective registry to determine whether laparoscopic surgery is to be
preferred over open surgery in patients undergoing a left lateral hepatic
sectionectomy and participating in an enhanced recovery programme.
In the participating randomizing centres patients, medical and nursing staff
(not the operating surgeon) will be blinded for the type of intervention using
an abdominal dressing until post operative day 4.
To capitalise on both centres with and without preference for laparoscopic
liver surgery, and to thereby acquire an uninterrupted prospective series of
patients, all non-randomizable patients undergoing a left lateral sectionectomy
will approached to participate in the prospective registry. The combination of
a RCT and a prospective registry will improve overall power and strengthen the
external validity and generalizability of study results.

The ORANGE II * Trial investigates whether the open or laparoscopic procedure
is superior in patient undergoing a segment 2-3 resection (left lateral
sectionectomy). This will be expressed by a shorter time to functional recovery
after one of these two procedures.
In the Netherlands only 5% of all liver resections are performed
laparoscopically and the vast majority of all 2-3 resection are still resected
by a subcostal or midline incision. Therefore, the standard surgical approach
for lesions in liver segment 2-3 is still the open procedure In Dutch
participating centres. Patients are only eligible for laparoscopy if they agree
to participate and randomize for their surgical treatment in the ORANGE II *
Trial or if the surgeon explicitly objects to open surgery. Patients randomized
in the ORANGE II * Trial will have a 50% chance of getting a laparoscopic
intervention. If they do not wish to participate in the trial they will be
offered the open segment 2-3 resection as part of the standard surgical care.

Both standard treatments will be compared. Extra burden for patients is filling
in questionnaires. 4 questionnaires at admission, a patient diary during
admission, 3 questionnaires at discharge, 3 questionnaires after 10 days, 4
questionnaires at 3 months, 6 months and 1 year after discharge. Furthermore,
patients will recieve an additional ultrasound to diagnose incisional hernia.