Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial.

PURPOSE: To compare outcomes after laparoscopic versus open major liver resection (hemihepatectomy) mainly for primary or metastatic cancer. The primary outcome measure was time to functional recovery. Secondary outcomes included morbidity, quality of life (QoL), and for those with cancer, resection margin status and time to adjuvant systemic therapy. PATIENTS AND METHODS: This was a multicenter, randomized controlled, patient-blinded, superiority trial on adult patients undergoing hemihepatectomy. Patients were recruited from 16 hospitals in Europe between November 2013 and December 2018. RESULTS: Of the 352 randomly assigned patients, 332 patients (94.3%) underwent surgery (laparoscopic, n = 166 and open, n = 166) and comprised the analysis population. The median time to functional recovery was 4 days (IQR, 3-5; range, 1-30) for laparoscopic hemihepatectomy versus 5 days (IQR, 4-6; range, 1-33) for open hemihepatectomy (difference, -17.5% [96% CI, -25.6 to -8.4]; P < .001). There was no difference in major complications (laparoscopic 24/166 [14.5%] v open 28/166 [16.9%]; odds ratio [OR], 0.84; P = .58). Regarding QoL, both global health status (difference, 3.2 points; P < .001) and body image (difference, 0.9 points; P < .001) scored significantly higher in the laparoscopic group. For the 281 (84.6%) patients with cancer, R0 resection margin status was similar (laparoscopic 106 [77.9%] v open 122 patients [84.1%], OR, 0.60; P = .14) with a shorter time to adjuvant systemic therapy in the laparoscopic group (46.5 days v 62.8 days, hazard ratio, 2.20; P = .009). CONCLUSION: Among patients undergoing hemihepatectomy, the laparoscopic approach resulted in a shorter time to functional recovery compared with open surgery. In addition, it was associated with a better QoL, and in patients with cancer, a shorter time to adjuvant systemic therapy with no adverse impact on cancer outcomes observed.

The orange-III study: the use of preoperative laxatives prior to liver surgery in an enhanced recovery programme, a randomized controlled trial.

BACKGROUND: This study evaluates the effect of preoperative macrogol on gastrointestinal recovery and functional recovery after liver surgery combined with an enhanced recovery programme in a randomized controlled setting. METHODS: Patients were randomized to either 1 sachet of macrogol a day, one week prior to surgery versus no preoperative laxatives. Postoperative management for all patients was within an enhanced recovery programme. The primary outcome was recovery of gastrointestinal function, defined as Time to First Defecation. Secondary outcomes included Time to Functional Recovery. RESULTS: Between August 2012 and September 2016, 82 patients planned for liver resection were included in the study, 39 in the intervention group and 43 in the control group. Median Time to First Defecation was 4.0 days in the intervention group (IQR 2.8-5.0) and 4.0 days in the control group (IQR 2.9-5.0), P = 0.487. Median Time to Functional Recovery was day 6 (IQR 4.0-8.0) in the intervention group and day 5 (IQR 4.0-7.5) in the control group, P = 0.752. No significant differences were seen in complication rate, reinterventions or mortality. CONCLUSION: This randomized controlled trial showed no advantages of 1 sachet of macrogol preoperatively combined with an enhanced recovery programme, for patients undergoing liver surgery.

Laparoscopic versus open resections in the posterosuperior liver segments within an enhanced recovery programme (ORANGE Segments): study protocol for a multicentre randomised controlled trial.

BACKGROUND: A shift towards parenchymal-sparing liver resections in open and laparoscopic surgery emerged in the last few years. Laparoscopic liver resection is technically feasible and safe, and consensus guidelines acknowledge the laparoscopic approach in the posterosuperior segments. Lesions situated in these segments are considered the most challenging for the laparoscopic approach. The aim of this trial is to compare the postoperative time to functional recovery, complications, oncological safety, quality of life, survival and costs after laparoscopic versus open parenchymal-sparing liver resections in the posterosuperior liver segments within an enhanced recovery setting. METHODS: The ORANGE Segments trial is an international multicentre randomised controlled superiority trial conducted in centres experienced in laparoscopic liver resection. Eligible patients for minor resections in the posterosuperior segments will be randomised in a 1:1 ratio to undergo laparoscopic or open resections in an enhanced recovery setting. Patients and ward personnel are blinded to the treatment allocation until postoperative day 4 using a large abdominal dressing. The primary endpoint is time to functional recovery. Secondary endpoints include intraoperative outcomes, length of stay, resection margin, postoperative complications, 90-day mortality, time to adjuvant chemotherapy initiation, quality of life and overall survival. Laparoscopic liver surgery of the posterosuperior segments is hypothesised to reduce time to functional recovery by 2 days in comparison with open surgery. With a power of 80% and alpha of 0.04 to adjust for interim analysis halfway the trial, a total of 250 patients are required to be randomised. DISCUSSION: The ORANGE Segments trial is the first multicentre international randomised controlled study to compare short- and long-term surgical and oncological outcomes of laparoscopic and open resections in the posterosuperior segments within an enhanced recovery programme. TRIAL REGISTRATION: ClinicalTrials.gov NCT03270917 . Registered on September 1, 2017. Before start of inclusion. PROTOCOL VERSION: version 12, May 9, 2017.

Pan-European survey on the implementation of robotic and laparoscopic minimally invasive liver surgery.

BACKGROUND: Laparoscopic and robotic minimally invasive liver surgery (MILS) is gaining popularity. Recent data and views on the implementation of laparoscopic and robotic MILS throughout Europe are lacking. METHODS: An anonymous survey consisting of 46 questions was sent to all members of the European-African Hepato-Pancreato-Biliary Association. RESULTS: The survey was completed by 120 surgeons from 103 centers in 24 countries. Median annual center volume of liver resection was 100 [IQR 50-140]. The median annual volume of MILS per center was 30 [IQR 16-40]. For minor resections, laparoscopic MILS was used by 80 (67%) surgeons and robotic MILS by 35 (29%) surgeons. For major resections, laparoscopic MILS was used by 74 (62%) surgeons and robotic MILS by 33 (28%) surgeons. The majority of the surgeons stated that minimum annual volume of MILS per center should be around 21-30 procedures/year. Of the surgeons performing robotic surgery, 28 (70%) felt they missed specific equipment, such as a robotic-CUSA. Seventy (66%) surgeons provided a formal MILS training to residents and fellows. In 5 years' time, 106 (88%) surgeons felt that MILS would have superior value as compared to open liver surgery. CONCLUSION: In the participating European liver centers, MILS comprised about one third of all liver resections and is expected to increase further. Laparoscopic MILS is still twice as common as robotic MILS. Development of specific instruments for robotic liver parenchymal transection might further increase its adoption.

International multicenter propensity score matched study on laparoscopic versus open left lateral sectionectomy.

BACKGROUND: Despite a lack of high-level evidence, current guidelines recommend laparoscopic left lateral sectionectomy (LLLS) as the routine approach over open LLS (OLLS). Randomized studies and propensity score matched studies on LLLS vs OLLS for all indications, including malignancy, are lacking. METHODS: This international multicenter propensity score matched retrospective cohort study included consecutive patients undergoing LLLS or OLLS in six centers from three European countries (January 2000-December 2016). Propensity scores were calculated based on nine preoperative variables and LLLS and OLLS were matched in a 1:1 ratio. Short-term operative outcomes were compared using paired tests. RESULTS: A total of 560 patients were included. Out of 200 LLLS, 139 could be matched to 139 OLLS. After matching, baseline characteristics were well balanced. LLLS was associated with shorter operative time (144 (110-200) vs 199 (138-283) minutes, P < 0.001), less blood loss (100 (50-300) vs 350 (100-750) mL, P = 0.005) and a 3-day shorter postoperative hospital stay (4 (3-7) vs 7 (5-9) days, P < 0.001). CONCLUSION: This international multicenter propensity score matched study confirms the superiority of LLLS over OLLS based on shorter postoperative hospital stay, operative time, and less blood loss thus validating current guideline advice.

Implementation and outcome of minor and major minimally invasive liver surgery in the Netherlands.

BACKGROUND: While most of the evidence on minimally invasive liver surgery (MILS) is derived from expert centers, nationwide outcomes remain underreported. This study aimed to evaluate the implementation and outcome of MILS on a nationwide scale. METHODS: Electronic patient files were reviewed in all Dutch liver surgery centers and all patients undergoing MILS between 2011 and 2016 were selected. Operative outcomes were stratified based on extent of the resection and annual MILS volume. RESULTS: Overall, 6951 liver resections were included, with a median annual volume of 50 resections per center. The overall use of MILS was 13% (n = 916), which varied from 3% to 36% (P < 0.001) between centers. The nationwide use of MILS increased from 6% in 2011 to 23% in 2016 (P < 0.001). Outcomes of minor MILS were comparable with international studies (conversion 0-13%, mortality <1%). In centers which performed ≥20 MILS annually, major MILS was associated with less conversions (14 (11%) versus 41 (30%), P < 0.001), shorter operating time (184 (117-239) versus 200 (139-308) minutes, P = 0.010), and less overall complications (37 (30%) versus 58 (42%), P = 0.040). CONCLUSION: The nationwide use of MILS is increasing, although large variation remains between centers. Outcomes of major MILS are better in centers with higher volumes.