1. Introduction

Emergency laparotomy has been associated with high morbility rate, long hospital stay and high mortality rate. A Retrospective study performed in USA with 37553 patients including in it, showed a mortality rate of 14 percent after emergency laparotomy [1]. Other study in Danmark with 4920 patients in it, confirmed high mortality rate after emergency laparotomy, with a 19.5 percent [2]. A study designed in United Kingdom identified the importance of emergency laparotomy cares standardisation to reduce high morbimortality rate [3]. Implementation of Enhancement Recovery After Surgery(ERAS) measures have been widely studied in elective surgery since Ljunquist deployed them [4]. ERAS measures scope within elective surgery has dramatically reduced hospital stay by up to 30 percent without readmission increase. Medical postoperative complications have also declined with ERAS measures scope. But, nevertheless, these measures haven´t been used as much in emergency surgery due to mainly, impossiblity of preoperative measures application because their emergency condition and on the other hand, patients´ diversity, different comorbidities and different systemic impacts such as shock, sepsis and Systemic Inflammatory Response Syndrome (SIRS) [ 1, 5]. Use of ERAS measures in patients suffering from colon obstruction due to neoplasm was associated with a 20-percentage decrease of hospital stay. Postoperative complications decreased a 20 percentage in ERAS group compared with conventional measures in Clavien-Dindo scale type II, III and IV, although, there weren´t significant (p=0.12) [6]. ERAS measures aplication in colon cáncer obstruction has been studied in several studies. There are 3 cohort studies comparing ERAS vs conventional care in Emergency colon obstruction surgery [7. 8, 9]. In all of them, a reduction of hospital stay was demostrated in ERAS group (2 days, 3 days and 3 days, respectively). In the three studies, a postoperative complications decrease rate was shown. Dimitrov et cols [10] study confirmed decrease rate in hospital stay and postoperative complications in ERAS Group in cáncer colon obstruction.

2. Hypotesis

This study has beengenerated from this prospective, multicentre, observational cohort study will help to verify or better understand the suspected benefits of ERAS protocols regarding long-term survival in patients who have undergone colorectal surgery. The data will also help future research studies. anteriormente sobre este tema.

3. Methods and Analysis

Design

A prospective, multicentre, observational cohort study in patients who meet the inclusion criteria. Setting This study will be conducted with different European hospitals promoved by Spanish multimodal rehabilitation group (GERM). All hospital selected received prior standarised the protocol of the study and they have to ask for local committee approbal.

Inclusion criteria

• All adult patients (aged >18 years) with a diagnosis of Malignant obstruction colorectal cancer. Informed consent will be obtained from all subjects who will participate in the study voluntarily.

• ASA I, II and III

• No more than 5 days from symptoms onset.

• Absence of proximal colon severe dilatation (no more than 8 centimeters), severe malnutrition.

• No Inmunocompromised patients

• Patients suffer from segmentary colectomy, with or without anastomosis with o witjhout lateral ileostomy

• Patients suffer from Hartmann procedure. 

Exclusion criteria

• Patient refusal.

• Patients under 18 years of age.

• ASA IV • Stent colocation

• ICU stay more than 2 days

• Peritonitis

• Out of protocol if patient would need total parenteral nutrition (NPT) during postoperative or Clavien-Dindo more or equal than II.

The research project will be monitored closely by a certified external auditor to ensure that study activities are carried out in accordance with the protocol, good clinical practice and applicable regulatory requirements. Local study documents can be selected for a local audit at participating hospitals. Data quality will also be audited.

4. Limitations of the study

The limitations are those inherent to a prospective, non-randomised study, including difficulty in recruiting patients due to potential structural or multidisciplinary team problems and inappropriate number of patients in any of the arms due to a very high or very low level of compliance.

Follow-up

The study is planned to start in March 2025, and for the survival study only patients with a minimum follow-up of 1 years will be considered. However, patients will still be recruited until the end of the 1-year period (March 2025) to allow study of the secondary objectives. The follow-up plan is as follows: tumour markers (used to monitor colorectal neoplasia)-carcinoembryonic antigen determined at [3, 6, 9, 12] and cancer antigen 19.9 determined at [3, 6,9,12,] CT performed at [6, 12] and complete colonoscopy performed at 1-year after surgery.

5. Data Collection and Data Management Data will be collected using an online data collection form via a secure, password-protected platform with predefined data fields at each centre. The variables to be collected are displayed in (Table 1). For the purpose of the study, we will record the following: complications at 60-day follow-up (surgical complications, infectious complications, cardiovascular complications), each rated as mild, moderate or severe and also according to the Clavien-Dindom classification; perioperative mortality (the number and percentage of deaths within 60 days of surgery); hospital stay, defined as the duration from the date of the end of surgery to the date of discharge from the hospital (in days); overall survival (the number and percentage of deaths that occur from the intervention to the end of follow-up); disease-free survival (the number of patients alive and with no cancer recurrence from the intervention period to the end of follow-up); and recurrence of the disease (detected by CT or FCC), from the day of the intervention until the end of follow-up. The data collection platform Castor EDC (https://www. castoredc. com) will be used. This platform complies with all applicable laws and regulations. All identifiable data collected, processed and stored for the purposes of the project will be kept confidential at all times and comply with Good Clinical Practice guidelines for Research and the General Data Protection Regulation

6. Statistical analysis

Given that the main objective (survival) may be subject to aspects inherent to each centre, irrespective of the intervention, it will be necessary to create comparable groups using the propensity score method (propensity score matching). A descriptive analysis of the data will be carried out. Qualitative variables will be represented by a frequency distribution of the percentages for each category, and quantitative variables will be explored using the Kolmogorov-Smirnov conformity test. The association between factors will be investigated using hypothesis contrast tests, with a comparison of proportions when both variables are qualitative (I2, Fisher’s exact test), a comparison of mean when one of them is quantitative (Student’s t-test, analysis of variance (ANOVA), and the MannWhitney U test or the Kruskall-Wallis test if they do not follow a normal distribution) and a bivariate correlation (Pearson correlation coefficient) when both are quantitative or the Spearman correlation if the conditions for application of the former are not met. For comparisons in related samples when one of them is quantitative, Student’s t-test and/or ANOVA will be used (Wilcoxon or Friedman’s test if they do not follow a normal distribution). The analysis will be completed using multivariate regression models. A survival analysis will be performed using the Kaplan-Meier method, and the log-rank test will be used for survival comparisons between groups. Effects will be considered to be significant with a p value of less than 0.05.

References

1. Al-Temimi MH, Griffee M, Enniss TM, Preston R, Vargo D, Overton S, et al. When Is Death Inevitable after Emergency Laparotomy? Analysis of the American College of Surgeons National Surgical Quality Improvement Program Database. J Am Coll Surg. 2012; 215(4): 503-11.

2. Vester-Andersen M, Lundstrøm LH, Møller MH, Waldau T, Rosenberg J, Møller AM. Danish Anaesthesia Database Mortality and postoperative care pathways after emergency gastrointestinal surgery in 2904 patients: a population-based cohort study. Br J Anaesth. 2014; 112: 860–870.

3. Huddart S, Peden C, Quiney N. Emergency major abdominal surgery – ‘the times they are a-changing’. Colorectal Dis. 2013; 15: 645–9.

4. Ljungqvist O, Scott M, Fearon KC. Enhanced recovery after surgery: a review. JAMA Surg 2017 ;152(3): 292–298.

5. Daniel VT, Ingraham AM, Khubchandani JA, Ayturk D, Kiefe CI, Santry HP. Variations in the delivery of emergency general surgery care in the eraof acute care surgery. Jt Comm J Qual Patient Saf. 2019; 45(1): 14–23.

6. Aggarwal A, Irrinki S, Kurdia KC, Khare S, Naik N, Tandup C, et al. Modified Enhanced Recovery After Surgery (ERAS) Protocol Versus Non-ERAS Protocol in Patients Undergoing Emergency Laparotomy for Acute Intestinal Obstruction: A World J Surg. 2023;47(12): 2990-2999.

7. Lohsiriwat V. Enhanced recovery after surgery vs conventional care in emergency colorectal surgery. World J Gastroenterol. 2014; 20: 13950– 5. 8. Shida D, Tagawa K, Inada K, Nasu K, Seyama Y, Maeshiro T, et al. Modified enhanced recovery after surgery (ERAS) protocols for patients with obstructive colorectal cancer. BMC Surg. 2017; 17: 18.

9. Shang Y, Guo C, Zhang D. Modified enhanced recovery after surgery protocols are beneficial for postoperative recovery for patients undergoing emergency surgery for obstructive colorectal cancer: A propensity score matching analysis. Medicine (Baltimore) 2018; 97: e12348.

10. Dimitrov, VM. Application of Enhanced Recovery after Surgery Protocols in Colorectal Cancer, Complicated by Malignant Bowel Obstruction: a Review of the Literature. Journal of Biomedical and Clinical Research. 2021; 14(1): 10- 15.