The impact of retractor SPONGE-assisted laparoscopic surgery on duration of hospital stay and postoperative complications in patients with colorectal cancer (SPONGE trial): study protocol for a randomized controlled trial

The SPONGE trial is the first randomized controlled trial to evaluate the impact of the use of the retractor sponge during laparoscopic colorectal surgery on duration of hospital stay and postoperative complications. Since no alternative for the Trendelenburg position has been available, the clinical relevance of the effects related to this position has never been investigated. Recently, results of a pilot study suggested that avoidance of the Trendelenburg position might reduce the postoperative hospital stay [10]. This effect could potentially be explained by a more stable perioperative hemodynamic status, which may make patients less prone to develop complications. Since this pilot study was a nonrandomized retrospective matched analysis, the risk of bias is considerable. Therefore, a randomized trial is warranted to estimate an unbiased effect of the Trendelenburg position on postoperative complications and hospital stay.

This trial is relevant because the number of (non-)surgical postoperative complications after colorectal surgery is substantial and result in a relatively high morbidity and mortality rate [19, 20]. Even though laparoscopic colorectal surgery is associated with certain benefits as a shorter hospital stay, less blood loss, and a faster recovery of bowel function, the risk on postoperative cardiopulmonary complications is not evidently lower than in open surgical procedure. A systematic review on nonsurgical complications following laparoscopic or open surgery for colorectal cancer showed no difference in the risk of pulmonary complications (pooled analysis for laparoscopy in colon cancer (OR 0.78, 95 % CI 0.53 to 1.13) and in rectal cancer (OR 1.19, 95 % CI 0.74 to 1.90)) [21]. Significantly fewer cardiac adverse events were observed in patients undergoing colectomy, but not in those undergoing rectal surgery (OR 0.28, 95 % CI 0.11 to 0.71 and OR 0.85, 95 % CI 0.41 to 1.71, respectively). This could be a result of the more extensive surgery, longer operation time, and higher risk on overall postoperative morbidity in rectal surgery [22]. Several studies presented the effects of the Trendelenburg position on perioperative cardiopulmonary parameters, but postoperative data are lacking [7, 8, 23‐26]. Besides, the effect of a patient’s position as an independent factor is hard to evaluate because the perioperative hemodynamic parameters are partly influenced by pneumoperitoneum, which is the CO₂ gas insufflation in the abdominal cavity [3].

The retractor sponge may provide two additional advantages. In the Trendelenburg position, cephalad excursion (sliding) of the patient while on the operation table can be problematic, particularly for obese patients or when the tables are positioned at steep angles. Sliding can cause skin and neuropathic injuries and can disturb the surgical procedure [27, 28]. Some devices used for sliding prevention, such as shoulder braces or headrests, can induce neuromuscular injuries, particularly brachial plexus injury, and are therefore not recommended [27]. In sponge-assisted surgery, patients are operated in horizontal position with no risk of sliding. Another potential benefit of a horizontal position is a more comfortable ergonomic position for the surgeon. The retractor sponge allows the surgeon to work with laparoscopic instruments in a horizontal line with the patient, which may reduce tension in the arms and neck. Unfortunately, we are not able to investigate these potential ergonomic benefits because this trial is performed at only one center with extensive experience in sponge-assisted surgery.

This study uses the cmRCT design. This design aims to overcome shortcomings of classic RCTs such as slow recruitment, disappointment bias in patients randomized to the control arm, and poor generalizability due to enrollment of only a small proportion of eligible patients [14, 29]. Trial recruitment within the PLCRC cohort is expected to be more efficient because patients are recruited from a large patient cohort, and only patients randomly selected for the intervention are informed about the intervention. In popular low risk interventions, such as the one used in the present study, the risk of disappointment bias or dropout in the control arm, due to a strong preference for the sponge intervention, is therefore diminished.

A challenging aspect of the cmRCT design is the fact that multiple trials are conducted simultaneously within one cohort. In patients eligible for multiple trials, interference of endpoints between trials might occur. As mentioned earlier, some of the patients eligible for the SPONGE trial will have participated in the RECTAL BOOST study [14]. Patients having received the boost intervention potentially have a higher risk on acute toxicity than patients who undergo standard chemoradiation [30], which could result in perioperative complications and thereby prolonged hospital stay. In order to balance the number of patients treated with the experimental boost intervention between both arms, stratified randomization is required. The main advantage of stratified randomization is the systematic balance of factors, which may influence outcome measures between treatment groups resulting in trial efficiency, increased power and less need for (biased) post-hoc analysis [31]. Furthermore, stratified randomization enables the possibility to detect potential interactions between the boost intervention and outcome measures of the SPONGE trial. On the other hand, the more trials conducted within one cohort, the more strata required for randomization in every new trial. This will result in complex trial coordination, treatment allocation, and trial administration. Having too much trial-induced strata may result in overstratification. This could lead to unfilled strata, unequal distribution of stratification factors, or the need for adjusted analysis [31‐33]. In addition, it is yet unclear if there is such as a limit in number of interventions per patient within the cmRCT design. In our cohort, these new methodological challenges should be taken into account when a new trial is initiated. In the future, expertise of clinicians will be essential in the design of new cmRCT-based trials because overlap of endpoints must be considered in an early stage since this could affect potential recruitment rates and thereby the succeeding of a trial.

A limitation of this study is that the trial is performed in a single center by a surgeon experienced with sponges. In the near future, other centers may participate, which will enhance the generalizability of the results. In addition, the trial is performed unblinded. The pragmatic cmRCT design makes blinding impossible because information must be provided to randomly selected patients because they have to choose whether they want to undergo sponge-assisted or standard surgery. Clinicians cannot be blinded because perioperative use of the sponge must be reported in the operation report for safety reasons. To minimize observer bias in physicians responsible for discharge of the patients, we use an objective primary endpoint in the form of a discharge checklist. Both intervention arm and control patients will be assessed by this checklist provided to attending physicians. According to the cmRCT design, patients in the control arm are not aware of the fact that a sponge intervention is available, which may minimize disappointment bias.

In conclusion, this trial will evaluate the clinical effects of sponge-assisted laparoscopic colorectal surgery compared to the standard Trendelenburg positioning. Results of the trial will be applicable to other institutions performing laparoscopic colorectal surgery, as well as to other laparoscopic pelvic procedures that make use of the Trendelenburg position.