Stefanus J. van Rooijen

Importance: Colorectal surgery is associated with substantial morbidity rates and a lowered functional capacity. Optimization of the patient's condition in the weeks prior to surgery may attenuate these unfavorable sequelae. Objective: To determine whether multimodal prehabilitation before colorectal cancer surgery can reduce postoperative complications and enhance functional recovery. Design, Setting, and Participants: The PREHAB randomized clinical trial was an international, multicenter trial conducted in teaching hospitals with implemented enhanced recovery after surgery programs. Adult patients with nonmetastasized colorectal cancer were assessed for eligibility and randomized to either prehabilitation or standard care. Both arms received standard perioperative care. Patients were enrolled from June 2017 to December 2020, and follow-up was completed in December 2021. However, this trial was prematurely stopped due to the COVID-19 pandemic. Interventions: The 4-week in-hospital supervised multimodal prehabilitation program consisted of a high-intensity exercise program 3 times per week, a nutritional intervention, psychological support, and a smoking cessation program when needed. Main Outcomes and Measures: Comprehensive Complication Index (CCI) score, number of patients with CCI score more than 20, and improved walking capacity expressed as the 6-minute walking distance 4 weeks postoperatively. Results: In the intention-to-treat population of 251 participants (median [IQR] age, 69 [60-76] years; 138 [55%] male), 206 (82%) had tumors located in the colon and 234 (93%) underwent laparoscopic- or robotic-assisted surgery. The number of severe complications (CCI score >20) was significantly lower favoring prehabilitation compared with standard care (21 of 123 [17.1%] vs 38 of 128 [29.7%]; odds ratio, 0.47 [95% CI, 0.26-0.87]; P = .02). Participants in prehabilitation encountered fewer medical complications (eg, respiratory) compared with participants receiving standard care (19 of 123 [15.4%] vs 35 of 128 [27.3%]; odds ratio, 0.48 [95% CI, 0.26-0.89]; P = .02). Four weeks after surgery, 6-minute walking distance did not differ significantly between groups when compared with baseline (mean difference prehabilitation vs standard care 15.6 m [95% CI, -1.4 to 32.6]; P = .07). Secondary parameters of functional capacity in the postoperative period generally favored prehabilitation compared with standard care. Conclusions and Relevance: This PREHAB trial demonstrates the benefit of a multimodal prehabilitation program before colorectal cancer surgery as reflected by fewer severe and medical complications postoperatively and an optimized postoperative recovery compared with standard care. Trial Registration: trialregister.nl Identifier: NTR5947.

BACKGROUND: Colorectal cancer (CRC) is the second most prevalent type of cancer in the world. Surgery is the only curative option. However, postoperative complications occur in up to 50% of patients and are associated with higher morbidity and mortality rates, lower health related quality of life (HRQoL) and increased expenditure in health care. The number and severity of complications are closely related to preoperative functional capacity, nutritional state, psychological state, and smoking behavior. Traditional approaches have targeted the postoperative period for rehabilitation and lifestyle changes. However, recent evidence shows that the preoperative period might be the optimal moment for intervention. This study will determine the impact of multimodal prehabilitation on patients' functional capacity and postoperative complications. METHODS/DESIGN: This international multicenter, prospective, randomized controlled trial will include 714 patients undergoing colorectal surgery for cancer. Patients will be allocated to the intervention group, which will receive 4 weeks of prehabilitation (group 1, prehab), or the control group, which will receive no prehabilitation (group 2, no prehab). Both groups will receive perioperative care in accordance with the enhanced recovery after surgery (ERAS) guidelines. The primary outcomes for measurement will be functional capacity (as assessed using the six-minute walk test (6MWT)) and postoperative status determined with the Comprehensive Complication Index (CCI). Secondary outcomes will include HRQoL, length of hospital stay (LOS) and a cost-effectiveness analysis. DISCUSSION: Multimodal prehabilitation is expected to enhance patients' functional capacity and to reduce postoperative complications. It may therefore result in increased survival and improved HRQoL. This is the first international multicenter study investigating multimodal prehabilitation for patients undergoing colorectal surgery for cancer. TRIAL REGISTRATION: Trial Registry: NTR5947 - date of registration: 1 August 2016.

Colorectal anastomotic leakage (CAL) is a major surgical complication in intestinal surgery. Despite many optimizations in patient care, the incidence of CAL is stable (3–19%) [1]. Previous research mainly focused on determining patient and surgery related risk factors. Intraoperative non-surgery related risk factors for anastomotic healing also contribute to surgical outcome. This review offers an overview of potential modifiable risk factors that may play a role during the operation. Two independent literature searches were performed using EMBASE, Pubmed and Cochrane databases. Both clinical and experimental studies published in English from 1985 to August 2015 were included. The main outcome measure was the risk of anastomotic leakage and other postoperative complications during colorectal surgery. Determined risk factors of CAL were stated as strong evidence (level I and II high quality studies), and potential risk factors as either moderate evidence (experimental studies level III), or weak evidence (level IV or V studies). The final analysis included 117 articles. Independent factors of CAL are diabetes mellitus, hyperglycemia and a high HbA1c, anemia, blood loss, blood transfusions, prolonged operating time, intraoperative events and contamination and a lack of antibiotics. Unequivocal are data on blood pressure, the use of inotropes/vasopressors, oxygen suppletion, type of analgesia and goal directed fluid therapy. No studies could be found identifying the impact of body core temperature or mean arterial pressure on CAL. Subjective factors such as the surgeons' own assessment of local perfusion and visibility of the operating field have not been the subject of relevant studies for occurrence in patients with CAL. Both surgery related and non-surgery related risk factors that can be modified must be identified to improve colorectal care. Surgeons and anesthesiologists should cooperate on these items in their continuous effort to reduce the number of CAL. A registration study determining individual intraoperative risk factors of CAL is currently performed as a multicenter cohort study in the Netherlands. • There are many intraoperative risk factors of CAL which are modifiable by improvements in perioperative care. • Multicenter registration study is necessary to determine the exact contribution of each intraoperative risk factor of CAL. • Modifiable risk factors are: <36° Celsius, anemia, blood loss and transfusion, events and contamination, duration of surgery. • Even in non-diabetes patients perioperative hyperglycemia increases the risk of CAL. • Surgeons and anesthesiologists should cooperate in their continuous effort to reduce the number of CAL.

BACKGROUND: Considering the relation between preoperative functional capacity and postoperative complications, enhancing patients' functional capacity before surgery with a prehabilitation program may facilitate faster recovery and improve quality of life. However, time before surgery is short, mandating a multimodal and high-intensity training approach. This study investigated feasibility and safety of a prehabilitation program for colorectal cancer. METHODS: Multimodal prehabilitation was offered to patients eligible for participation and they were assigned to an intervention or control group by program availability. The prehabilitation program consisted of the following four interventions: in-hospital high-intensity endurance and strength training, high-protein nutrition and supplements, smoking cessation, and psychological support. Program attendance, patient satisfaction, adverse events, and functional capacity were determined. RESULTS: Fifty patients participated in this study (prehabilitation 20, control 30). Program evaluation revealed a high (90%) attendance rate and high level of patient satisfaction. No adverse events occurred. Endurance and/or strength were improved. Eighty-six percent of patients with prehabilitation recovered to their baseline functional capacity 4 weeks postoperatively, 40% in the control group (P < 0.01). CONCLUSIONS: Multimodal prehabilitation including high-intensity training for colorectal cancer patients is feasible, safe, and effective. A randomized controlled trial (NTR5947) was initiated to determine whether prehabilitation may lower morbidity and mortality rates in colorectal surgery.