Enhanced recovery after surgery (ERAS) interventions and outcome from colorectal surgery

Abstract: Although immense progress has been made in the fields of chemo- and radiotherapy during the last decades, surgery is still the ultimate cure for the majority of patients with colorectal cancer. Since colorectal cancer most often presents at a high age and in patients often suffering from a large burden of comorbidity, it is important to develop strategies to improve postoperative recovery and outcome, not only for the patient, but also from a health economic perspective. ERAS (Enhanced Recovery After Surgery) is an evidence-based concept aiming to reduce surgical stress, shown to reduce perioperative morbidity, improve postoperative recovery and shorten length of stay (LOS). Today, the international ERAS® Society Interactive Audit System (EIAS) includes a database containing more than 80 000 patients, each patient with more than 300 perioperative variables recorded. The database is a valuable source for research and a guide for surgical centres to sustain and improve principles of perioperative care. Within the research field of ERAS, our research group identified two major questions that need further investigation. First, single interventions included in the ERAS protocol require further evaluation regarding the impact on the protocol as a whole. Second, most studies have so far been focusing on short-term outcomes after surgery. The effect of an ERAS-program on long- term outcome is however, largely unknown. The overall aim of this thesis was to investigate these topics and hopefully fill some of the knowledge gaps concerning these questions. In paper I we evaluated the effect of perioperative fluid management on short-term postoperative outcomes and 5-year survival after surgery. This single-center cohort study included patients with colorectal cancer operated between 2002 to 2007. In all, 911 patients were enrolled. Patients receiving < 3000 mL iv fluid on the day of surgery were compared with patients receiving > 3000 mL. A restrictive fluid management was associated with shorter LOS (mean 5.6 vs 9.0 days, p < 0.001), lower risk of complications (odds ratio (OR) 0.44, 95 % confidence interval (CI) (0.28 – 0.71)) and symptoms delaying discharge (OR 0.47, 95 % CI (0.32 - 0.70)). The risk of cancer specific death was significantly reduced (hazard ratio (HR) 0.45, 95 % CI (0.25 – 0.81)). The study concluded a possible association between a restrictive fluid regimen and improved short- and long-term outcomes. In paper II the aim was to compare robotic and laparoscopic rectal tumor surgery within an ERAS setting regarding short-term outcomes and compliance to the ERAS protocol. This single-center cohort study included 47 patients operated with laparoscopic technique between January 2011 to April 2014 and 72 patients operated with robotic technique between April 2014 to January 2017. Robotic surgery was associated with shorter LOS (median 3 vs 7 days, p < 0.001), lower rate of complications (25 % vs 49 %, p < 0.01) and a lower conversion rate to open surgery (11 % vs 34 %, p = 0.002). Results endured in multivariate analysis. Compliance to the ERAS protocol showed no difference between groups. The conclusion, in this single-center cohort study, was that robotic rectal tumor surgery demonstrated superior short-term outcomes compared to laparoscopic rectal tumor surgery. In paper III the Swedish part of the international ERAS database was used to compare short- term outcome in patients operated on with robotic, laparoscopic and open rectal tumor surgery. Compliance to the ERAS® Society Guidelines was compared between groups. This multi- center retrospective cohort study included 3125 patients between January 2010 to February 2020. Robotic surgery showed similar complication rates compared to open surgery (35.9 % vs 40.9 %, OR 1.15, 95% CI (0.93, 1.41)) and laparoscopic surgery (35.9 % vs 31.2 %, OR 0.88, 95% CI (0.71, 1.08)). LOS was shorter in the robotic group, median 6 days vs 9 days in the open group (incidence rate ratio (IRR) 1.35, 95% CI (1.27, 1.44)) and 7 days in the laparoscopic group (IRR 1.14, 95% CI (1.07, 1.21)). Robotic surgery had a lower conversion rate compared to laparoscopic surgery (8.3 % vs 18.0 %, OR 2.58, 95 % CI (1.85, 3.60)). Pre- and intraoperative compliance to the ERAS protocol were similar between groups. In conclusion, this multi-center cohort study demonstrated shorter LOS in robotic surgery vs open and laparoscopic surgery and lower conversion rate to open surgery in the robotic group vs the laparoscopic group. In paper IV the aim was to identify predictors for anastomotic leakage (AL) in patients operated with anterior resection (AR) included in the Swedish part of the international ERAS database. Altogether 1900 patients were investigated between January 2010 to February 2020, 155 patients with AL and 1745 patients without AL. Obesity (OR 1.71, 95 % CI (1.04, 2.80)), male gender (OR 1.88, 95 % CI (1.28, 2.75)), duration of primary surgery (OR 1.13, 95 % CI (1.02, 1.24)), peritoneal contamination (OR 1.78, 95 % CI (1.01, 3.16)) and surgery late in the study period (OR 1.89, 95 % CI (1.18, 3.01)) were all independent predictors for AL. Patients suffering from AL had longer LOS (median 7 vs 15 days, p < 0.001) and higher rate of reoperations (69.7 % vs 6.6 %, p <0.001) compared to patients without AL. No difference in pre- and intraoperative compliance was seen between groups. In conclusion, this multi-center cohort study showed that male gender, obesity, duration of surgery, surgery late in the study period and peritoneal soiling were independent predictors for AL.

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