The results of this study support the thesis that the adoption of the ERAS protocol is effective and applicable in patients with colorectal cancer clinically staged T4, reducing significantly their LOS without affecting surgical postoperative outcomes. It is interesting to note that the decreased compliance with postoperative items does not affect the main ERAS outcome, suggesting the importance of the pre/intraoperative phase, especially patient counseling regarding advantages and duties of the ERAS protocol.
Since the first report by Kehlet et al  back in 1997, the adoption of fast track protocols in elective colorectal surgery has shown to reduce postoperative length of stay and results in a faster recovery when compared to traditional care [14-16].
However, the impact of fast track protocols on patients affected by advanced colorectal cancer has never been investigated. Many studies that compared ERAS to standard of care analyze all stages of colorectal cancer as a single group [17,18]. As a matter of fact, T4 colorectal cancer patients’ undergoing surgical resections are a minority (5-8%) and probably their weight is not influential. On the contrary, in other trials, patients with complex and/or multi organ resections and/or patients who were previously treated with neoadjuvant chemo radiotherapy are excluded in order to limit the heterogeneity of the study population [20-22]. The primary reasons being that a larger number of patients are exposed to more complex surgery and, therefore, are more likely to develop postoperative complications. Clearly, they would represent a mark in the analysis of outcomes such as complication rates and LOS.
Nevertheless, patients treated with ERAS protocol from Gatt, Fosmo and Feng, who all excluded either multi-visceral resections or advanced stage of disease from their studies, do not differ from those of Gouvas and Nanavati who included T4 resections, with regard to median postoperative LOS (5 days; 5 days and 5.5 days vs 5.5 days and 4,75 days respectively).
Another explanation for the exclusion of advanced stage colorectal cancer patients in ERAS trials, lies in the belief that they would have a more difficult compliance with some specific perioperative items such as the avoidance of abdominal drains, early urinary catheter removal, early feeding and mobilization
Lately those items have been the focus of a debate about their nature, since they could be considered markers of both protocol compliance and recovery . Since many postoperative items are strongly linked to the onset of postoperative complications it is difficult to figure out whether a given patient had better recovery because he was eating and ambulating early or whether he tolerated early eating and walked early thanks to rapid recovery. For the aforementioned reasons we have included in our study group all cT4 patients undergoing colorectal resections under an established ERAS protocol, with no exception. All patients were included in the analysis of results even in case of complex surgery and multiorgan resections. However, in such cases, a part of the ERAS principles could not be respected and the overall postoperative compliance was scarce. Despite a lower compliance, the study group obtained better outcomes in terms of PLOS and time to tolerate solid food compared to patients treated with traditional care.
Some other institutions focused their research on special subgroups of patients undergoing colorectal surgery such as patients affected by Crohn’s disease [24,25] and elderly patients [26-29], proving that even fragile patients could benefit from a faster recovery obtained through the ERAS protocol. Small series by Feroci et al  and Kisialeuski et al  confirmed a lower adherence to overall ERAS items in elderly compared to younger patients, especially regarding mobilization and i.v. fluid therapy duration, while they recorded similar median postoperative LOS in the ERAS groups regardless of compliance.
However, lower level of compliance for both caregivers and patients, was found for some intra and postoperative items, inter alia minimally invasive approach (50% for T4a VS 7% for T4b), drainage of abdominal cavity (10%), postoperative analgesia (47%) and early urinary catheter removal (55%), which are to be related to the advanced nature of the disease.
Minimal invasive approach is considered a fundamental tool to maximize the results of enhanced recovery and two RCTs already compared the adoption of ERAS protocols between open and laparoscopic surgery with or without an implementation with fast track. A combination of ERAS with laparoscopy results in a significant faster recovery compared with all other combinations (Open + ERAS, Laparoscopy + standard, Open + standard). However, the Open approach + ERAS also reduces the LOS, thus demonstrating a success of the ERAS program [32,33].
Even if not recommended by guidelines[34-36], feasibility and safety of laparoscopic resection in T4 colorectal tumors have been investigated by some series concluding that, despite the increased odds of conversion, in specialized centers and selected patients laparoscopy can be applied to patients with T4 colorectal tumors without worse long term outcomes [37-44]. In our study, we treated laparoscopically with an R0 resection 37 patients out of 82; in nine patients it was necessary to complete the operation with a conversion to open surgery. However, the number of patients who underwent laparoscopic resections, did not differ significantly in the two groups (p=0,83); therefore, the beneficial effects of laparoscopic surgery were present in equal manners in both the study group and the control group.
Although there are guidelines for implementing an enhanced recovery protocol for colorectal surgery, variation in the number and definition of protocol components, as well as variation in the criteria for adherence, contributes to difficulties in determining which components are most important for improving patient outcomes [45-47]. Our results suggest that a complex surgery with an expected overall lower compliance to ERAS items should not be a deterrent to fast track application, considering the benefits in terms of faster recovery, with no differences in terms of complications.
Limitations of this analysis are the retrospective nature of the study, which is also a single unit study, the lack of contemporaneous controls and the small sample size of the study group. The small sample size does not permit a risk adjustment analysis for factors as complications and confounding factors; in the face of a huge average effect on the primary outcome, the lack of specificity of the effect is a major limitation. However, it should be take into account that some ERAS strategies, such as antimicrobial prophylaxis, prevention of hypothermia, thoracic epidural anesthesia during open surgery, but also laparoscopy in colon surgery, are considered the current ‘standard of care’, therefore it may be considered unethical and difficult to perform randomized trials to evaluate the benefits of each of the ERAS items. Further multicentric prospective studies with lager sample size are warranted to help define the benefits of ERAS protocol in advanced colorectal patients.