Surgical outcomes and factors associated with postoperative complications of colorectal cancer in a Colombian Caribbean population: Results from a regional referral hospital

Abstract Introduction Colorectal cancer is the most common malignant neoplasm of the gastrointestinal tract. Its incidence and mortality vary markedly at a global level. Assessing the epidemiological behavior of this condition allows reevaluating diagnostic, therapeutic and prognostic options, based on new findings. In Colombia, few studies have correlated variables associated with surgical and oncological outcomes in this type of cancer. Then, the aim of this study was to evaluate the surgical outcomes and factors associated with postoperative complications of colorectal cancer in a Colombian Caribbean Population. Methods Retrospective cross‐sectional study, including patients with a histopathological diagnosis of colorectal cancer who underwent open or laparoscopic surgery, during a period of two years (2018–2020), from a regional referral hospital. Clinical history variables were collected. Frequencies and prevalence ratios were calculated. Results A total of 84 patients were finally included. Adenocarcinoma of non‐special type with advanced clinical stages was the most prevalent (72.6%). Rectal neoplasia (45.2%) was the most frequent anatomical subsite, followed by proximal colon (p = 0.026). The anatomical subsite of the neoplasm, intraoperative complication (PR 1.38; 95% CI, 1.21–1.59, p = 0.001) and intensive care stay (PR 1.062; 95% CI, 1.01–1.12, p = 0.048) were associated with postoperative outcome. Conclusions The anatomical subsite of the neoplasm location, the presence of intraoperative complications and the stay in intensive care may be associated with the surgical and oncological outcome of individuals with colon cancer from the Colombian Caribbean region.


| INTRODUCTION
Colorectal cancer is the most common malignant neoplasm of the gastrointestinal tract. Its incidence and mortality vary considerably at a global level. According to the GLOBOCAN data, by 2020, colorectal cancer was the second most frequent (1 931 590 cases -10% of total cases) and the second most deadly (935 173 cases-9.4% of total number of deaths), below lung cancer. 1 Similarly, in Colombia, colorectal cancer is the third most frequent cancer in both sexes, being surpassed by breast and prostate cancer. 1 It is the second most frequent cancer in women with an incidence of 16.7 cases per 100 000 women and 17.3 cases per 100 000 men. 1 This represented approximately 10% of the total number of new cancer cases in Colombia. 1 In Cartagena, the local health analysis carried out in 2019 found that neoplasms ranked third in frequency of cancer mortality, 2 making them one of the public health priorities.
Surgical treatment is the most common treatment for resectable colorectal cancer, and during the last decades, it has presented great improvements in terms of preoperative evaluation, instruments, surgical techniques, intraoperative monitoring and postoperative care. 3 Laparoscopic surgery, as opposed to open surgery, is recommended in patients without obstruction, perforation or local invasion. A consensus study published a few years ago by McNair et al, 4 identified important perioperative domains to evaluate in colon and rectal oncological surgery. 4 Oncological outcomes included long-term survival, cancer recurrence and resection margins, and operative outcomes included anastomotic leakage, perioperative survival, surgical site infection, stoma-related complications, and conversion to open procedure. 4 The authors concluded that such domains must be constantly evaluated and taken into account in order to define interventions based on the behavior of populations. In Colombia, few studies have correlated variables associated with surgical and oncological outcomes in this type of cancer, 5 and among the objectives of global surgery, 6 the need to produce evidence on the outcomes and progress of oncological surgery in the treatment of cancer has been highlighted, in order to control the burden of this disease, reduce health costs and catastrophic expenses, especially in low-and middle-income countries, such as Colombia. 7,8 The Colombian Caribbean region is one of the regions with the greatest inequality and difficulties in access to health care, which influences the general outcomes described in the literature on colorectal cancer. Currently, there is no evidence that has studied the relationship of surgical and oncological behavior with colorectal cancer outcomes in this region, preventing the application of in-hospital and out-of-hospital strategies to improve the quality of care and outcomes. Studies currently underway seek to describe the correlation between genotypic and phenotypic expression of colorectal cancer in this region, which is mainly composed of Afro-descendant, mixed race and indigenous populations, in order to define the safest and most effective interventions for the control and resolution of this disease.
Taking into account this gap in evidence, and the importance of knowing these outcomes to correlate them with findings in the molecular and genetic study of colorectal cancer in this particular population, the aim of this study was to evaluate the surgical outcomes and factors associated with postoperative complications of colorectal cancer in a Colombian Caribbean Population.

| Study design and participants
A retrospective cross-sectional study was carried out, evaluating the surgical outcomes and factors associated with postoperative complications of patients with colorectal cancer who underwent surgery in a regional tertiary center, by analyzing the medical records. This is a regional referral center that receives patients from the Caribbean region, especially those with limited resources. Annually, the gastroenterology surgery unit has historically received approximately 30 cases of colorectal cancer that need to be managed surgically. In the study period (January 2018-February 2020), a total of 96 patients were received.
Patients were included if they met all the following criteria: (1) had been operated on by the surgeons of the gastrointestinal surgery unit; (2) had a definitive diagnosis of cancer and classification by histopathological study; (3) had a complete medical history, for the analysis of clinical data; and (4) were 18 years of age or older. Patients who had been previously operated for the same cause, who had incomplete data and those who came from a region other than the Colombian Caribbean region were excluded in order to avoid discrepancies in the clinical, oncologic and epigenetic behavior of colorectal cancer in the region. After the application of inclusion and exclusion criteria, 84 patients were finally included.

| Data extraction
Information was collected on clinical variables such as age, sex, type of surgical procedure schedule, lesion location, anatomical subtype, pre-surgical anesthetic classification ASA (American Society of Anesthesiologists), 9

| Outcomes assessed
The primary endpoints evaluated were: postoperative complication (defined as the appearance of local or systemic symptoms associated with the alteration of the normal evolution of the patient after surgery), recovery time (defined as the time from the surgical procedure to the restoration of the patient's functional capacity [e.g., initiation of the oral route, among others]), postoperative morbidity (defined as the occurrence of significant morbidity, with the need for intensive care admission or longer hospital stay compared to the average) and mortality (defined as death between the time of the surgical procedure, until hospital discharge). 4,10 The secondary endpoints were the factors that could predict complications and mortality.

| Statistical analysis
Quantitative variables were measures of central tendency type aver-

| RESULTS
A total of 84 patients were included, who underwent surgery for a diagnosis of colorectal cancer. The mean age was 59.5 ± 17.1 years.
45.2% (n = 38) of the patients were male and 51.1% (n = 43) of the procedures were performed on an emergency basis. The most frequent lesion location was the rectum with 45.2% (n = 38), followed by the sigmoid and ascending colon (16.6% and 11.9%, respectively).
According to the ASA classification, the majority were categorized as ASA III (51.1%, n = 43). It was found that 52.1% (n = 43) had hemoglobin values higher than 11 g/dl. Likewise, 55.9% (n = 47) of the patients had albumin values between 3.1 and 3.5 mg/dl. About 50% of the patients included had no carcinoembryonic antigen (CEA) report, while 33.3% (n = 28) obtained results greater than 5 μg/L ( Table 1) Table 3). The most commonly reported type of neoplasm was adenocarcinoma (72.6%, n = 61) with moderate histological differentiation (39.2%, n = 33). The relationship between pathological features of the disease such as stage and histopathological diagnosis with tumor location is described in Table 4.  Table 6.
Bivariate analysis yielded significant associations between the presence of postoperative complication and other variables for T A B L E 1 Description of preoperative and clinical variables of the study population.    (2) many patients underwent emergency surgery, which does not allow for adequate preoperative monitoring (e.g., metabolic or nutri- However, open surgery was the preferred modality (65.4%) followed by laparoscopy (31.2%) and robotic surgery (3.4%). 21 They also found that laparoscopic and robotic surgery were associated with lower inhospital mortality, fewer complications, shorter length of stay, which may be related to the elective nature of the procedure and lower degrees of tumor malignancy. Finally, when excluding patients with advanced stages, they found that laparoscopic surgery continued to be associated with better outcomes and lower costs than open surgery, while robotic surgery was associated with higher costs without significant benefits in perioperative outcomes compared to laparoscopic surgery. 21 In Colombia, several studies have been carried out in the main cities of the country, analyzing the incidence and mortality of all types of colon and rectal cancer. Authors have found an average crude incidence rate of colon cancer of 9.0 vs. a mortality of 8.5. These data are lower than those found in Colombian cities, such as Cali, 22 Bucaramanga, 23 Manizales, 24 and Pasto. 25  An aspect to highlight about the behavior of the outcomes in the approach to colorectal cancer and the need to continuously evaluate this phenomenon, is the search for and actual calculation of the impact of certain factors related to epigenetics, such as ethnicity. 28 Evidence suggests that the performance of screening tests and the evolution of new cases vary between regions, making it difficult to extrapolate with confidence all the results found in the literature. 28 It has been observed that in rural and marginalized areas belonging to low-and middle-income countries, where there is a considerable volume of population (mainly due to farming and livestock activities or armed conflict situations), most of whom are elderly, there are inequities in education and screening interventions, which would explain difficulties in access to and compliance with therapeutic regimens and strict follow-up, which increases mortality. 29,30 Taking into account, the aggressive behavior of colorectal cancer observed in the population studied, it can be inferred, for example, that the population of the rural area with lower education and greater economic hardship, are late in presenting gastrointestinal symptoms suggestive of the presence of cancer, which would explain the frequency of late stages of diagnosis. Therefore, these findings could support that in similar populations, which also have a high prevalence of comorbidities and are also exposed to tropical diseases, personalized strategies should be designed to promote screening and early detection of cancer.
Although this was not the case, future studies could investigate the specific impact of belonging to the rural area as a risk factor for worse

| LIMITATIONS
The limitations of the present study include its cross-sectional and retrospective descriptive nature. This limits the extrapolation of results and interferes with the interpretation of these results. Additionally, during data collection, incomplete or partial reporting of data in the clinical history was observed, which is a reflection of the fractionation of patient care, probably in multiple institutions, which make latent the need for the application of an organized protocol that guarantees the highest quality in the care of patients with colorectal surgery to improve morbimortality and prognosis.

| CONCLUSIONS
The anatomical subsite of the neoplasm location, the presence of intraoperative complications and the stay in intensive care may be

ACKNOWLEDGMENTS
We thank the gastrointestinal surgeons of the participating institution, and the members of Grupo Prometheus y Biomedicina Aplicada a las Ciencias Clínicas working team.

FUNDING INFORMATION
This study was financed by the research office of the Universidad de Cartagena, through the projects identified with acts 78 and 114.