Predictive model for early postoperative stomal complications in colorectal cancer: A systematic review

Abstract

BACKGROUND

Stomal complications though small in early postoperative period, but poses significant morbidity, therapeutic challenge, delay in adjuvant treatment and sometimes even leads to mortality. Predictive model for early detection of stomal complications is important to improve the outcome. A model including patients and disease related factors, intraoperative surgical techniques and biochemical markers would be a better determinant to anticipate early stomal complications. Incorporation of emerging tools and technology such as artificial intelligence (AI), will further improve the prediction.

AIM

To identify various risk factors and models for prediction of early post operative stomal complications in colorectal cancer (CRC) surgery.

METHODS

Published literatures on early postoperative stomal complications in CRC surgery were systematically reviewed between 1995 and 2024 from online search engines PubMed and MEDLINE.

RESULTS

Twenty-four observational studies focused on identifying various risk factors for early post operative stomal complications in CRC surgery were analyzed. Stomal complications in CRC are influenced by several factors such as disease factors, patient-specific characteristics, and surgical techniques. There are some biomarkers and tools loke AI which may play significant roles in early detection.

CONCLUSION

Careful analysis of these factors, changes in biochemical parameters, and application of AI, a predictive model for stomal complications can be generated, to help in early detection, prompt action to achieve better outcomes.

Key Words: Stomal complications; Colorectal cancer; Predictive model; Artificial intelligence; Patient’ factors; Surgeon factor; Disease factors; Biochemical markers

Core Tip: Early stomal complications following colorectal cancer surgery, increases the morbidity, hospital stay and delays the adjuvant treatment. Therefore, it is important to detect it before it is clinically become apparent. Prediction of stomal complications and early corrective measure is essential to improve the outcome. A predictive model utilizing patient factors, disease factors, surgeon factors, and biochemical parameters utilizing artificial intelligence may serve a determinant to anticipate early stomal complications.

INTRODUCTION

Overall, the incidence of ostomy in patients with colorectal cancer (CRC) ranges from 20% to 80%[1]. Various indications for stoma formation include intestinal obstruction, perforation, poor nutritional status, and precarious or low rectal anastomosis and preoperative neoadjuvant treatment[2]. The types of ostomies in CRC patients include end colostomy, loop colostomy, and loop ileostomy. The complication rate associated with these stomas varies between 25% and 60%, with the highest complication rate observed in end colostomy[3]. Early complications occurring within the first 30 days, postoperatively, can lead to significant morbidity, reducing the patient’s quality of life, delaying adjuvant therapy, and potentially resulting in mortality[4]. Common early postoperative stomal complications include high stoma output causing dehydration, oedema, ischemia, retraction, peristomal skin irritation and infection, acute parastomal herniation, and stoma obstruction and frank necrosis[5]. Developing a predictive model for the early detection of these complications is crucial for improving patient outcomes by enabling timely corrective measures. A predictive model incorporating patient and disease factors, technical factors, biochemical parameters, with use of artificial intelligence (AI), can play a significant role in the early detection. The present systematic review aimed to identify various risk factors and models for prediction of early post operative stomal complications in CRC surgery.

MATERIALS AND METHODS

We systematically reviewed published literature between 1995 and 2024 from online search engines PubMed and MEDLINE using the search terms CRC, stomal complications, early stomal complications, early prediction, patient factors, disease factors, biomarkers, AI and bullion operators like AND, OR, and NOT. We included only those publications which were relevant to early stomal complications. The secondary sources retrieved from these publications were identified through a manual search and assessed for relevance.

A total of 86 papers were identified with no duplicates, and, as a first step, no papers were excluded for other reasons (PRISMA flow diagram reported in Figure 1). Full manuscript was not available in 18, leaving 68 papers for further evaluation. As a second step, we excluded papers that were not pertinent to stomal complications in patients with CRC. Further, secondary sources retrieved from these publications were identified through a manual search and assessed for relevance. Finally, twenty-four studies were found focusing on identifying various risk factors for early post operative stomal complications in CRC surgery, were included in this study.

Figure 1 PRISMA flow diagram.

RESULTS

Based on literature review the factors which could possibly predict the early postoperative stomal complications in CRC have been categorized as patient related factors, disease related factors, technical factors and biomarkers (Figure 2).

Figure 2 Various factors predicting postoperative stomal complications. ASA: American Society of Anesthesiologists; CRP: C-reactive protein; NLR: Neutrophil-to-lymphocyte ratio; PCT: Procalcitonin; LDH: Lactate dehydrogenase; CAR: C-reactive protein to albumin ratio; NAR: Neutrophil-to-albumin ratio; GLR: Glucose-to-lymphocyte ratio; IMA: Ischemia-modified albumin; IL-6: Interleukin-6.

Patients-related factors

Several non-modifiable and modifiable patient-related factors can influence the outcome of a stoma. These factors include age, gender, nutritional status, diabetes, cardiovascular diseases, smoking, patients on immunosuppression, previous abdominal surgeries, and the American Society of Anesthesiologists status prior to surgery (Table 1). Elderly patients over 65 years of age are at a higher risk of stomal complications such as retraction and parastomal hernia, due to age-related changes in skin elasticity, healing capacity, and immune function[6-8]. Women are more likely to develop parastomal hernias because of differences in abdominal wall structure and body mass index[7] A study examining factors associated with the risk of stomal complications found a significant correlation with elderly patients, those classified as American Society of Anesthesiologists grade III or worse, and stomas not performed by a specialist colorectal surgeon[8,9].

Table 1 Studies on patient- and disease- related factors and stomal complications.

Factors	Findings	Ref.
Age and gender	Elderly (> 65 years) women are at a higher risk of stomal complications	Yuan et al[6], Dai et al[7], Saghir et al[8], Nastro et al[9], Fish et al[10], Bai et al[11]
Nutritional status	Malnutrition is an independent, modifiable risk factor for stomal complications	Yuan et al[6], Ba et al[29]
Comorbid status and smoking	Unoptimized comorbidities lead to poor healing and increase stomal compilations	Dai et al[7], Nastro et al[9], Fish et al[10], Bai et al[11], Ba et al[29], Souwer et al[30]
Long-term immunosuppression	Increases risk of postoperative infections, impair tissue healing and prolonged hospitalization	Yuan et al[6], Dai et al[7]
ASA status prior to surgery	Grade III or worse has a significant correlation with stomal complications	Dai et al[7], Saghir et al[8], Nastro et al[9]
Obesity	BMI > 25 kg/m2 increases the risk of stomal complications as well as adds to the intraoperative difficulty	Dai et al[7], Nastro et al[9], Parmar et al[14]
Stage of carcinoma	Higher the TNM stage, more is the risk of stomal complications	Dai et al[7], Fish et al[10], Bai et al[11]
Preoperative chemotherapy and/or radiotherapy	It adversely affects the healing process	Fish et al[10], Bai et al[11], Ba et al[29]

ASA: American Society of Anesthesiologists; BMI: Body mass index; TNM: Tumor-node-metastasis.

Malnutrition is an independent, modifiable risk factor for stomal complications[6]. About one third of patients experience moderate to severe malnutrition preoperatively. Inadequate nutrition can lead to immunosuppression, increase the risk of postoperative infections, impair tissue healing, and prolong recovery times for gastrointestinal function and hospitalization duration[6,7]. A body mass index over 25 is known to increase the risk of complications such as parastomal hernia and stoma prolapse due to excess pressure on the abdominal wall. Additionally, obesity can present technical challenges during surgery[7].

Other modifiable risk factors include unoptimized underlying comorbidities. Diabetes mellitus can lead to microangiopathies in end arteries, which reduces blood flow to the cut ends of bowel segments, further contributing to ischemia. Poor blood sugar control also impairs the function of white blood cells, which are essential for wound healing and create an environment conducive to bacterial growth. Similarly, the effects of impaired blood flow and reduced oxygen delivery are observed in patients with cardiovascular diseases, severe anaemia, and those who chew tobacco or smoke[9]. Studies have also identified that most common early stomal complication causing readmission is dehydration secondary to high stoma output. Predictive factors for high stoma output include comorbidity burden, old age and neoadjuvant radiotherapy or chemotherapy[10,11].

Disease-related factors

Factors affecting the stomal outcome include stage of cancer, concomitant chemotherapy, prior radiotherapy, perforated or obstructed tumor demanding emergency surgery (Table 1). Patients with locally advanced colorectal carcinoma often experience severe malnutrition and weakened rectus abdominis muscles due to factors such as intestinal absorption dysfunction, inadequate nutritional intake, and the consumption of nutrients by cancer cells. Furthermore, these patients frequently require more extensive surgical resections and endure greater physiological stress. As a result, patients with high tumor-nodes-metastasis staging who undergo stoma procedures are more susceptible to complications[7]. Additionally, preoperative chemotherapy and radiotherapy can adversely affect the healing process and can affect the stomal complications[10,11]. Emergency surgery and those not performed by the expert colorectal surgeons are associated with a higher complication rate due to lack of preoperative planning and urgent nature of the procedure[12].

Technical and surgeon related factors

Selecting an improper stoma site is a common and avoidable early complications. Poor site selection can result in issues like leakage, skin irritation, and difficulties in managing the stoma. Preoperative stoma marking by a stoma nurse/trained clinician can significantly reduce these complications[13]. Thus, emergency surgery, where preoperative stoma marking is not possible, have a higher risk of stomal complication than elective surgery[12-14]. Additionally, previous abdominal surgeries can alter the anatomical landscape, making stoma creation more challenging. The diameter of the stoma is critical for proper appliance fitting and to prevent issues like skin irritation and leakage. Usually, normal stomas size is around 2 to 3 cm in diameter. However, this size may change due to significant weight gain or loss, swelling, or prolapse[13,15]. Also, the stoma opening height, stoma type, skin folds around the stoma, and history of prior radiotherapy are found to be a risk factor for developing peristomal moisture-associated skin damage[16].

Another technical factor causing stomal ischemia is compromised arterial supply to the cut ends of the exteriorized segment of bowel. Reasons for devascularization include excessive trimming of mesentery or epiploic fat beyond 5 cm from the cut end of bowel, division of collateral blood supply during efforts to create adequate length for a tension-free colostomy, inadvertent division of the marginal artery[15]. Intraoperative indocyanine green fluorescence imaging, is valuable tool available today and may be use for assessing the vascularity at cut ends before stromal maturation. Ensuring an adequate length of the bowel segment brought to the skin and creating a tension-free stoma are essential for preventing complications such as stoma retraction and necrosis. However, it can be challenging in obese patients due to thick and short mesentery. Secure and appropriate suturing with fine absorbable sutures is essential to prevent mucocutaneous separation and stoma necrosis[7] (Table 2).

Table 2 Studies on technical and surgeon related factors.

Factors	Findings	Ref.
Stoma site selection	Preoperative stoma marking reduces complications	Dai et al[7], Qureshi et al[12], Park et al[13], Parmar et al[14]
Diameter of stoma	Diameter of stoma is critical for proper appliance fitting in preventing complications	Dai et al[7], Park et al[13], Ota et al[15], Wang et al[16]
Inadequate length and reduced vascularity of exteriorized bowel	Tension and ischemia at stoma site leads to disruption	Ota et al[15]
Suturing technique	Fine absorbable sutures are essential to prevent mucocutaneous separation and stoma necrosis	Dai et al[7]
Emergency surgery	Lack of preoperative planning increases the risk of complications	Qureshi et al[12], Park et al[13], Parmar et al[14]

Ideally, the stoma should be situated within the rectus abdominis muscle to provide support and minimize the risk of parastomal herniation. Abdominal wall reinforcement with mesh as a preventive measure for parastomal hernia may be considered[7]. Minimizing intraoperative blood loss through meticulous surgical techniques to control bleeding and preventing contamination during surgery contribute to improved wound healing. By employing these intraoperative strategies, surgeons can significantly reduce the risk of stoma-related complications, resulting in better patient outcomes and an enhanced quality of life[17].

Biochemical markers

Various biomarkers have been studied to detect body’s inflammatory and nutritional status. Preoperative and immediate postoperative abnormalities in these parameters are useful aid in predicting and preclinical detection of complications. CRC patients, especially with anorexia, malabsorption, local or systemic infection, obstruction or perforation, are prone to malnutrition and systemic inflammatory responses. These associated conditions can lead to poor healing, ischemia, and consequently, early stomal complications. Some of these biomarkers include C-reactive protein (CRP), the neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), lactate dehydrogenase, the CRP to albumin ratio, the neutrophil-to-albumin ratio, the glucose-to-lymphocyte ratio, globulin level, and ischemia-modified albumin (Table 3).

Table 3 Studies on role of biomarkers which may be useful in early detection of stomal complications.

Factors	Findings	Ref.
CRP, PCT	Both CRP and PCT have a NPV in ruling out septic complications. Threshold value for CRP is 170 to 190 on day 3 and 120 mg/dL to 140 mg/dL on day 4	Dai et al[7], Ramanathan et al[18], Giaccaglia et al[21], Kumar et al[22]
NLR	NLR predicts ischemic complications, threshold value being ≥ 3.54 preoperatively and ≥ 5.5 on postoperative day 7	Forget et al[20], Kumar et al[22]
NAR, GLR, GLB	NAR > 0.086, GLR > 3.662, and GLB ≤ 28 g/L are independent predictors of stomal complications	Yuan et al[6]

CRP: C-reactive protein; PCT: Procalcitonin; NPV: Negative predictive value; NLR: Neutrophil-to-lymphocyte ratio; NAR: Neutrophil-to-albumin ratio; GLR: Glucose-to-lymphocyte ratio; GLB: Globulin level.

CRP is one of the most commonly studied biomarkers. An increase in CRP levels is typically seen in response to trauma, including abdominal surgery, within the first 24 to 48 hours. These levels generally return to normal around the third postoperative day. A decrease or low CRP level on days three and four has a high negative predictive value for a lack of septic complications. Various studies have identified threshold values of 170 to 190 on day three and 120 mg/dL to 140 mg/dL on day four to serve marker indicators infections postoperative[7,18].

NLR is another inflammatory biomarker that can predict stomal ischemia. During the inflammatory response, neutrophil levels increase while lymphocyte levels often decrease. Neutrophils target ischemic areas by releasing inflammatory cytokines and free radicals, whereas lymphocytes help reduce inflammation and initiate the healing process[19]. A pre-operative NLR of 3.54 or higher has been correlated with post-operative complications. Similarly, a value of more than 5.5 on postoperative day 7 has also shown significant association with post-operative complications[20]. It is also noted that NLR is directly proportional to tumor stage[19]. PCT rises during inflammation, particularly in the presence of bacterial infections. Similar to CRP, PCT has a negative predictive value in ruling out potential septic complications. However, unlike CRP, PCT reaches its maximum usefulness later compared to CRP around postoperative day 5[21].

In a study on role of serum markers in predicting the anastomotic leaks in colorectal surgery, we found that serum levels of CRP, NLR, and interleukin-6 on postoperative day 3 were significantly associated with the development of leaks[22]. Extrapolating from above mentioned data, various inflammatory markers may be utilized to predict the onset of stomal complications, even prior to their clinical manifestation, especially ischemia and septic complications. A biomarker-based study involving patients with CRC undergoing enterostomy has identified that preoperative abnormal markers (neutrophil-to-albumin ratio > 0.086, glucose-to-lymphocyte ratio > 3.662, and globulin level ≤ 28 g/L) are independent risk factors for predicting early stoma-related complications. These markers serve not only as nutritional indicators but also as indicators of systemic inflammation and disease severity[6].

Role of AI

There are several studies on AI in the detection of complications in colorectal surgery (Table 4). AI has been found an assistant in surgical decision-making whether to create a stoma, opt for a loop ileostomy over a colostomy, and complications[23-25]. AI-assisted stomal education material is available that provide accurate and understandable information to patients[26]. AI algorithms with colorectal predictive and preventive models are well established in colorectal surgeries[23]. Studies have used artificial neural networking and machine learning to create new models and also to test the validity of the already existing models. AI can provide real-time navigation and enhance surgical precision using techniques like indocyanine green angiography and hyperspectral imaging[27]. Thereby, guiding the surgeon regarding vascularity at the cut end and preventing potential ischemic complications. AI integrated operation theatre may help in recognizing anatomical structures and surgical tools, through image segmentation and thereby optimize the surgical visualization. AI-driven simulations and feedback mechanisms can help to improve the surgical skills and the performance[28]. By using the sum of components of the AI as mentioned earlier in CRC surgical decision making[23], AI may play a crucial role in formulating a model for preventing and predicting stoma complications. AI can incorporate patient factor, disease factor, surgeon factor and biochemical markers, to generate a near ideal nomogram for accurate prediction of stomal complications.

Table 4 Publications on application of artificial intelligence and its role in stomal management.

Factors	Findings	Ref.
Surgical skill and decision-making	AI can predict the need and type of stoma whether end or loop. Deep learning model can predict the outcome better than logistic regression for complex combination of patient- and procedure-related variables. AI may help in assessment of surgical resection margins which can be applied to surgical decision making	Ghosh and Kumar[23], Kuo et al[24], Bektaş et al[25], Hassan et al[28]
Perfusion and oxygenation of exteriorized bowel	Techniques like ICG and HSI can provide precise information regarding perfusion and oxygenation, preventing potential ischemic complications	Spinelli et al[27]

AI: Artificial intelligence; ICG: Indocyanine green; HIS: Hyperspectral imaging.

The integration of real-time AI feedback in stoma surgery could enhance intraoperative decision-making, particularly in identifying risk factors and optimizing or modifying procedural techniques to minimize complications. AI-driven guidance could refine stoma placement, predict postoperative outcomes based on patient-specific variables, and provide surgeons with adaptive recommendations to mitigate adverse events. Various studies have constructed nomograms predicting early postoperative complications after surgery for CRC and internally validated using tools like machine learning and artificial neural networking[29-33]. There are not many studies on stomal complications. Also, none of these studies include all the factors which may affect the stomal outcomes. Based on literature review, authors propose a nomogram model, integrating various factors to predict stomal complications (Table 5). The proposed model requires further validation in prospective multicenter cohort studies to confirm its reproducibility across diverse clinical settings.

Table 5 Proposed nomogram model for prediction of stomal complications.

Factors	Criteria	Score1
Age, years	≤ 65	0
	> 65	1
Gender	Male	0
	Female	1
BMI, kg/m2	18.5-25	0
	> 25	1
Diabetes or cardiac comorbidities	No	0
	Yes	1
Tobacco abuse	No	0
	Yes	1
Long-term immunosuppression, > 3 months	No	0
	Yes	1
ASA status	< Grade III	0
	≥ Grade III	1
AJCC stage of carcinoma	Stage 1 or 2	0
	Stage 3 or 4	1
Preoperative chemotherapy and/or radiotherapy	No	0
	Yes	1
Type of surgery	Elective	0
	Emergency	1
Experience of surgeon	Specialist colorectal surgeon	0
	Trainee
	Senior registrar	1
Preoperative stoma markings	No	0
	Yes	1
Intraoperative difficulty related to length of exteriorized bowel or vascularity	No	0
	Yes	1
CRP level > 170 mg/dL on postoperative day 3	No	0
	Yes	1
NLR ≥ 3.54 preoperatively	No	0
	Yes	1
NLR ≥ 5.5 on postoperative day 7	No	0
	Yes	1
NAR > 0.086 on postoperative day 3	No	0
	Yes	1
GLR > 3.662 on postoperative day 3	No	0
	Yes	1
GLB ≤ 28 g/L on postoperative day 3	No	0
	Yes	1
Use of artificial intelligences	Yes	0
	No	1

¹Higher the total score, more is the risk of stomal complications.

BMI: Body mass index; ASA: American Society of Anesthesiologists; AJCC: American Joint Committee on Cancer; CRP: C-reactive protein; NLR: Neutrophil-to-lymphocyte ratio; NAR: Neutrophil-to-albumin ratio; GLR: Glucose-to-lymphocyte ratio; GLB: Globulin level.

DISCUSSION

Early stomal complications in CRC surgery is multifactorial and complex and are governed by interplay of various risk factors. A nomogram designed to predict these early stomal complications may facilitate preventive interventions like preoperative optimization, modification of surgical techniques, pre-emptive keen postoperative observation, and early confirmative imaging. For better interpretation of the results, it is essential to acknowledge limitations of this review. Various studies included in the review have a retrospective study design, which may introduce selection bias, and the omission of key socioeconomic factors, such as access to postoperative care and health literacy, could restrict the generalizability of findings, particularly for underserved populations.

CONCLUSION

Stomal complications in CRC are influenced by several factors such as disease factors, patient-specific characteristics, and surgical techniques. Careful incorporation of these factors, postoperative changes in biochemical parameters, and application of AI, a predictive model for stomal complications can be generated, to help in early detection, prompt action to achieve better outcomes.