Complications and postoperative ileus in laparoscopic versus open colectomy: A retrospective cohort study [version 1; peer review: 1 approved with reservations]

Background: Postoperative complications are a major concern after colorectal surgery, and can lead to an increased burden on patients and the healthcare system. Complications include postoperative ileus (POI) and prolonged postoperative ileus (PPOI). There are wellestablished risk factors and potential modifiable risk factors that affect the incidence of POI and PPOI, including invasive techniques, operative difficulty, perioperative blood loss, and delayed mobilization. We compared the incidence of POI,  PPOI, and other postoperative complications between laparoscopic colectomy and open colectomy. Methods: This retrospective review investigates 120 patients who underwent either laparoscopic or open colectomy in King AbdulAziz University Hospital in Jeddah, Saudi Arabia, between January 2016 and June 2019. Data were collected from patients’ electronic medical records. Patients were classified into laparoscopic and open colectomy groups. The main outcomes of interest were POI, PPOI and the overall complication rate. These outcomes were calculated and compared between the two groups. Results: The overall incidence of POI and PPOI was 4.2% and 15%, respectively. There was a higher incidence of POI in the laparoscopic approach group (7.2% vs. 1.5%, P=0.03); however, the incidence of PPOI was higher in the open approach group (20% vs. 9.1%, P=0.03). The open surgery group showed a higher rate of overall complications (P=0.001). The mean estimated blood loss was lower in the laparoscopy group (139.09±145.83 vs. 343.85±307.78 mL; P<0.001). Significant earlier mobilization was observed in the laparoscopic group (3.12±1.77 vs. 5.39±3.48 days; P<0.001). Open Peer Review


Introduction
Postoperative complications are often inevitable following abdominal surgeries. They range from altered postoperative recovery which does not require medical intervention, to life-threatening conditions requiring intensive care management and may lead to mortality. 1,2 Among these complications, postoperative ileus (POI) is still the most common postoperative problem causing delays in patient discharge, while anastomotic leak is considered the most important factor that leads to readmission within 30 days. 3 Along with other complications, POI and anastomotic leak contribute heavily to the economic burden on the healthcare system. 3 The incidence of POI across extensive studies was found to range from 10% to 30%, leading to a 29% increase in the length of stay (LOS) in the hospital. 4,5 The term ileus refers to the disability of gastrointestinal peristalsis, which is characterized by absent or decreased peristalsis that results in the accumulation of digestive secretions leading to intolerance to oral feeding, abdominal distention, abdominal pain, failure to pass flatus, absence of bowel movement, nausea, and vomiting. These complications increase the risk of aspiration pneumonia, malabsorption, and anastomosis leakage. 4 Normally, the functionality of the small intestine returns within 24-48 hours postoperatively, while the colon requires 48-72 hours of recovery. 6 In Saudi Arabia, data on surgical outcomes and the differences between laparoscopic and open approaches in terms of postoperative ileus are scarce. Our goal was to evaluate the incidence of POI and prolonged postoperative ileus (PPOI) as well as postoperative complication rates between the two different approaches, following colorectal surgery in our institution. This was with a view to assessing the potential contributing factors.

Setting and patient population
We conducted a retrospective cohort study at King AbdulAziz University Hospital (KAUH), a tertiary center in Jeddah, Saudi Arabia. Data of 134 adult patients who underwent colectomy for colorectal cancer from January 2016 to June 2019 were collected from the electronic medical database and reviewed. Patients were divided into two groups, laparoscopy, and laparotomy approach. A total of 14 patients were excluded due to their conversion from laparoscopy to open surgery. The final population size was 120.

Ethics statement
This study was approved by the Institutional Review Board of KAUH in 2019 (ref. . The need for obtaining patient consent was waived by the IRB.

Inclusion and exclusion criteria
All adult patients aged > 18 years that were diagnosed with non-metastatic colon or rectal cancer and who had undergone operation were extracted from the hospital's data base and included. Patients who had laparoscopic conversion to open, i.e. surgeries which started with laparoscopy that ended up being laparotomy were excluded. In addition, patients with disseminated cancer, concurrent procedure, or sepsis (in the form of peritonitis) were excluded from the study to avoid confounders. Patients with incomplete records were also excluded from the analysis of that particular entity.

Definition of variables
The data collected included demographic information (age, sex, Body Mass Index, comorbidities) as well as preoperative variables including diagnosis, neoadjuvant therapy, comorbidities, and previous abdominal surgeries. Intraoperative variables were also documented, including the American Society of Anesthesiologists (ASA) score, use of epidural anesthesia, colorectal procedure, approach (laparoscopy or open), stoma formation, estimated blood loss, blood transfusion, and procedure duration. All patients received a clear liquid diet 24 h after the operation and subsequently progressed to a regular diet. After the regular diet was tolerated and bowel movements returned to normal, the patient was discharged.
Postoperative variables included the type of analgesia, vomiting, abdominal distention, time of mobilization, time until clear and regular diets were tolerated, and the day of the first bowel movement. The length of hospital stay, from the time of operation until patient discharge, was also recorded. Readmission within 30 days and postoperative complications were assessed based on the Clavien-Dindo score. 7 POI was defined as the absence of first flatus and intolerance of an oral intake within three days, postoperatively, and PPOI was defined as the delayed passage of flatus with intolerance of an oral intake for more than three days, postoperative. 8

Statistical methods
Statistical analysis was performed using IBM SPSS Statistics Version 21.0.Mean AE standard deviation was used to describe the numerical data. Patient treatment and outcome related variables where represented as percentages and frequencies of the total population. Comparisons and the relationships between the groups were made using independent t-test, chi-square test, and bivariate correlation. The results were considered significant where the two-tailed P value ≤ 0.05.

Results
A total of 120 patients that were diagnosed with colorectal cancer who underwent different colonic procedures were included in this study (see Underlying data 23 ). The patients' baseline characteristics are presented in Table 1. Patients were divided into two groups: the laparoscopic approach group, 55 patients (45.8%); and the open approach group, 65 patients (54.2%). The age of the patients ranged from 22 years to 90 years, with a mean (SD) age of 61.36 AE 13.85 years. The patients were predominantly male (60%), and most of the cohort had colon cancer (67.5%). Over half of the patients were either overweight or obese (65%), and a third had diabetes mellitus (33.3%). Most patients were of ASA class 2 or 3 (92.5%).
Regarding operative variables, the majority were elective procedures (77.5%) and most had anastomoses (74.2%) ( Table 2). Most patients did not require blood transfusion, and among those who did, the average number of units transfused was 1.75 (SD, 0.46). Table 3 presents the postoperative outcomes including postoperative complications, POI, and PPOI in both the laparoscopic and the open approaches. The incidence of POI and PPOI in the study group was 4.2% and 15%, respectively. There was a higher incidence of POI in the laparoscopic approach (7.2% vs. 1.5%, P = 0.03); however, the incidence of PPOI was higher in the open approach (20% vs. 9.1%, P = 0.03 Regarding the incidence of postoperative complications, 59% of patients had no complications, while 41% had varying degrees of complications. The open approach showed a higher rate of complications-37 patients (56.9%), compared to 11 patients (20%) in the laparoscopic group. According to the Clavien-Dindo score, this difference was statistically significant (Table 3).

Discussion
Addressing the incidence of POI and PPOI is essential for determining the risk factors associated with these complications and can therefore help in decreasing their occurrence. In our study, the incidences of POI and PPOI following colorectal surgery were 4.2% and 15%, respectively, while the literature demonstrates that the incidence of POI is 10-30% and the incidence of PPOI is 2-54%. 4,5,9 Previous studies have demonstrated that the risk factors for POI and PPOI include more invasive approaches, operative difficulty, older age, perioperative blood loss, and delayed mobilization. 10,11 Our analysis showed that the open approach was associated with a significantly higher incidence of PPOI than the laparoscopic approach. In the literature, the open approach was identified as an independent risk factor for the development of an ileus. 9 At the same time, most of the patients with POI, which is a less severe form of ileus, were in the laparoscopic group. These results are more likely explained by the inflammatory and neurological responses to surgical trauma and increased requirements for narcotics, which are more pronounced in the open approach group. 12,13 It has been suggested that adherence to protocols of enhanced recovery after surgery could potentially decrease the incidence of POI. These protocols that recommend minimally invasive procedures, early ambulation, and early feeding. 14 Previous studies, 2,10,14 including a cross-sectional study conducted in 2013 in Isfahan, Iran, 6 have found that the occurrence of ileus is directly associated with the duration of the surgical procedure. However, the Iranian study solely focused on the duration of the operation, rather than the type of surgical approach used. 6 In our analysis, the duration of laparoscopic colectomy was significantly longer than that of the open procedure; however, this did not lead to an increase in the incidence of PPOI. Another study that observed 295 patients who underwent laparoscopic colectomy for colorectal cancer, also found that the duration of the operation has little impact on POI and PPOI. 15 Some studies speculate that the longer duration of the laparoscopic approach is due to the limited range of motion and flexibility of instruments, in addition to the two-dimensional view and the dependence on surgeon skill. 16 However, we do not agree with that statement in view of ongoing innovations, and the early exposure of trainees to laparoscopic surgery. There is the potential risk of bias, however, as it may be the case that more advanced disease that requires open surgery and multiorgan resection could contribute to prolonged operative time, POI, and PPOI. In terms of intraoperative complications, studies have shown that the higher the estimated blood loss, the higher the risk of developing POI. This is explained by the stimulation of the sympathetic stress response and its inhibition of bowel motility. 17 Many studies state that the open approach results in more blood loss and blood transfusions than the laparoscopic approach. 18,19 Our results have also shown a significant difference in blood loss between open surgery and laparoscopy (343.85 vs. 152.73 mL). The significant increase in bleeding in the open approach may have occurred due to the larger surgical incision. However, this could also be influenced by the fact that more advanced disease that requires major resection would be associated with more blood loss and a higher rate of transfusion.
Regarding the postoperative hospital course, our results have shown a significant earlier tolerance of regular diet in the laparoscopy group compared to the open group (5.44 vs. 8.94 days). This may be due to less trauma during the operation and the release of less amounts of stress hormones, allowing for early bowel recovery. 18 Patients who underwent laparoscopy showed earlier ambulation (3.12 vs. 5.39 days) because of the small surgical incision and less pain. Early mobilization in the laparoscopy group also helped to stimulate bowel function. Similar results on early regular diet tolerance and early mobilization in the laparoscopy group were observed in other studies. 12 The laparoscopic approach was associated with a significantly lower risk of overall complications and this supports our point of view. 13 Furthermore, our study has shown that the Clavien-Dindo score was lower in the laparoscopy group than in the open group. A recent study showed that the most common surgical complication is surgical site infection (SSI), while POI is the third most common complication. 20 In our study, the most frequent complications were POI and PPOI, followed by SSI. With regard to LOS, we found that it was shorter in the laparoscopy group compared to the open group. This was similar to the findings of a recent retrospective cohort study performed in the United States, which investigated both surgical approaches and robotic surgery, and showed that robotic and laparoscopic surgeries had shorter LOS than the open approach. 21 In addition, a better quality of life was observed in patients that underwent laparoscopic colectomy in a randomized controlled trial. 22 The study's main limitations were its retrospective nature, small number of patients, and the lack of standardized definitions of POI and PPOI. These results are limited to a small population in a single tertiary center, therefore not necessarily applicable to the general population and definitive conclusions cannot be made. Further studies with a larger sample size, involving multiple colonic diseases, are required to address this issue.

Conclusion
The incidence of both POI and PPOI were significantly influenced by the surgical approach used. The laparoscopic approach showed better postoperative mobilization and tolerance to regular diet. However, overall complications were more frequent in the open approach. Our suggestion for future studies is to address more extensive pre-and postoperative measures aimed at decreasing the incidence of POI, PPOI, and other complications of colorectal surgeries.

1.
Regarding the results of POI and PPOI: PPOI is any POI that extends beyond 3 days, thus, logically the numbers and percentages of PPOI are less than POI because some patients will resolve their postoperative ileus. However, in this article the numbers of POI is more than PPOI. Did they inverse the numbers? or when they say PPOI what they really mean is late onset of postoperative ileus?

2.
Again, good article and worth publishing after correction and clarification of those 2 points.
Thank you.

Is the work clearly and accurately presented and does it cite the current literature? Yes
Is the study design appropriate and is the work technically sound? Yes

Are sufficient details of methods and analysis provided to allow replication by others? Yes
If applicable, is the statistical analysis and its interpretation appropriate?