Risk factors influencing sphincter preservation in laparoscopic radical rectal cancer surgery

Abstract

BACKGROUND

The surgical management of rectal cancer is continuously advancing, with a current emphasis on minimising the need for a permanent stoma. Understanding the risk factors influencing sphincter preservation is crucial for guiding clinical decision-making and optimising preoperative patient evaluation.

AIM

To examine the risk factors influencing sphincter preservation in laparoscopic radical rectal cancer surgery.

METHODS

A retrospective analysis of the demographics, preoperative and intraoperative data, and pathological findings of 179 patients with rectal cancer who underwent laparoscopic radical rectal cancer surgery at our hospital between January 2022 and December 2023 was conducted. These clinical data were compared between two groups: Patients with sphincter preservation and those without, categorised as the sphincter-preserved and sphincter-unpreserved groups, respectively.

RESULTS

Of the 179 patients analysed, 150 were in the sphincter-preserved group and 29 were in the sphincter-unpreserved group. Tumour height was significantly greater in the sphincter-preserved group compared to the sphincter-unpreserved group. Conversely, elevated levels of carcinoembryonic antigen, carbohydrate antigen 19-9, and plasma D-dimer were significantly higher in the sphincter-unpreserved group. Significant differences were also observed between the two groups in terms of place of residence, presence of colonic polyps, neoadjuvant chemotherapy, preoperative radiotherapy, mucinous adenocarcinoma, nerve invasion, and tumour height. No significant differences were observed for other parameters. Logistic regression analysis identified colonic polyps, mucinous adenocarcinoma, nerve invasion, and tumour height as independent risk factors for sphincter preservation.

CONCLUSION

Several risk factors influencing sphincter preservation in laparoscopic radical rectal cancer surgery were identified. These factors could be valuable tools for guiding clinical decision-making and optimising preoperative patient evaluations.

Key Words: Rectal cancer; Laparoscopic surgery; Sphincter preservation; Risk factors; Preoperative evaluation

Core Tip: This study aimed to identify key risk factors associated with achieving tumour resection and sphincter preservation in patients with rectal cancer by analysing clinical data from 179 patients who underwent laparoscopic radical rectal cancer surgery. Patients with nerve invasion, mucinous adenocarcinoma, and tumours in the lower rectum were at higher risk of sphincter non-preservation. Logistic regression analysis identified nerve invasion, mucinous adenocarcinoma, and tumour height as independent risk factors for sphincter preservation. Conversely, sphincter preservation rates were higher among patients with concomitant colonic polyps. These findings provide valuable insights for identifying high-risk patients and guiding targeted interventions and preoperative evaluations.

INTRODUCTION

Surgical resection remains the mainstay of treatment for rectal cancer (RC), with the primary objectives being complete tumour removal to minimise recurrence and maintain the patient's quality of life[1]. For most patients, the optimal surgical approach prioritises reducing the need for a permanent colostomy and achieving restorative anterior resection[2]. Laparoscopic techniques have gradually replaced traditional open surgery, becoming the preferred intervention for RC treatment[3]. However, undergoing abdominoperineal resection with a permanent colostomy poses significant physical, psychological, and economic challenges for patients, often making it challenging to accept[4]. Sphincter preservation is, therefore, a critical clinical concern. Identifying factors influencing sphincter preservation is essential to enhance awareness of the risk of permanent stoma and to guide more effective clinical interventions and preoperative assessments[5]. This study analysed and compared the clinical data of the included patients to identify risk factors affecting sphincter preservation in patients with RC undergoing laparoscopic radical surgery.

MATERIALS AND METHODS

Inclusion and exclusion criteria

The clinical data of 179 patients who underwent laparoscopic radical RC surgery at our hospital between January 2022 and December 2023 were retrospectively analysed.

Inclusion criteria: Patients diagnosed with rectal malignancy who underwent laparoscopic radical RC surgery.

Exclusion criteria: Patients with non-primary tumours and other cancerous lesions; open surgery; metastatic disease; incomplete tumour resection; and incomplete clinical data.

This study was conducted in accordance with the Declaration of Helsinki. Preoperative informed consent was obtained from all patients and their families. The study was approved by the Ethics Committee of Shaanxi Provincial People's Hospital.

Data collection

The hospital information system was used to obtain the following patient-related information:

Basic information: Sex, age, place of residence, body mass index, history of previous abdominal surgery, history of recent aspirin use, smoking history, alcohol consumption history, time since onset of first symptoms or diagnosis, degree of tumour differentiation, and tumour-node-metastasis stage.

Preoperative variables: Duration of preoperative care, bowel preparation time, neoadjuvant chemotherapy, and preoperative radiotherapy.

Preoperative comorbidities: History of hypertension, diabetes mellitus, coronary artery disease, colonic polyps, rectal polyps, tumours causing obstruction, tumours with bleeding, peripheral vascular lesions of the lower extremities, hypoproteinaemia, anaemia, and fever of ≥ 37 °C.

Other clinical parameters: Pelvic effusion, tumour height, maximum transverse tumour diameter, American Society of Anaesthesiologists grading, nerve invasion, vascular invasion, and mucinous adenocarcinoma.

Preoperative biochemical indicators: White blood cells, platelets, albumin, glucose, serum potassium, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), prothrombin time, and D-dimer levels.

Statistical analysis

Data analysis was performed using SPSS 27.0 software. The normality of the measurement data was determined using the Shapiro-Wilk test. Normally distributed data are presented as the mean ± SD, while data with skewed distributions are expressed as M (P25, P75). Between-group comparisons were performed using the Mann-Whitney U test or independent samples t-test, as appropriate. Categorical data are expressed as n (%) and analysed using the χ² test. Logistic regression analysis was used to identify risk factors affecting sphincter preservation in patients undergoing laparoscopic radical RC surgery, with a significance level set at α = 0.05.

RESULTS

Analysis of patients undergoing laparoscopic radical RC surgery

A total of 199 patients were initially considered for the study. However, six cases were excluded due to incomplete tumour resection and positive pathological margins; 13 cases were excluded due to palliative surgery resulting from distant metastasis or the presence of other cancerous lesions; and one case was excluded due to the need for intermediate open surgery due to severe abdominal adhesions.

Among the remaining 179 patients with RC included in the study, 150 underwent sphincter preservation, while 29 had sphincter removal, all performed through laparoscopic radical surgery. The clinical data of the sphincter-preserved group and the sphincter-unpreserved group were subsequently analysed.

Comparison of clinical data between the two groups

The sphincter-preserved group and the sphincter-unpreserved group were comparable in terms of baseline characteristics. However, statistically significant differences were observed between the two groups regarding tumour height, serum markers (CEA and CA19-9), place of residence, presence of comorbid colonic polyps, neoadjuvant chemotherapy, and nerve invasion.

Most of the patients in the sphincter-unpreserved group were from rural areas and had tumours in the lower to middle rectum. This group also exhibited a higher prevalence of nerve invasion and concomitant mucinous adenocarcinoma. In contrast, most patients in the sphincter-preserved group had tumours in the upper rectum and were more likely to have combined colonic polyps (Table 1). Furthermore, CEA and CA19-9 Levels were significantly higher in the sphincter-unpreserved group compared to the sphincter-preserved group (P < 0.05).

Table 1 Comparison of clinical data between sphincter-preserved and sphincter-unpreserved groups, n (%).

Factors	Sphincter-preserved group (n = 150)	Sphincter-unpreserved group (n = 29)	Statistics	P value
Age (years)	67 (59, 72)	65 (57, 73)	0.719	0.472
Sex			0.001	0.985
Male	98 (65.3)	19 (65.5)
Female	52 (34.7)	10 (34.5)
Residence			3.951	0.047
Rural	63 (42.0)	18 (62.1)
Urban	87 (58.0)	11 (37.9)
BMI (kg/m2)	22.8 ± 3.2	22.5 ± 3.3	0.587	0.558
Time since onset of first symptoms or diagnosis (months)	2 (1, 6)	3 (2, 7)	1.225	0.220
Duration of preoperative care (days)	7 (5, 9)	7 (6, 10)	0.925	0.355
Preoperative bowel preparation time (days)	6 (4, 7)	6 (5, 7)	0.731	0.465
Colonic polyps	72 (48.0)	8 (27.6)	4.097	0.043
Rectal polyps	20 (13.3)	1 (3.4)	1.438	0.230
Tumours with bleeding	107 (71.3)	20 (69.0)	0.066	0.797
Tumours causing obstruction	22 (14.7)	1 (3.4)	1.821	0.177
Neoadjuvant chemotherapy	20 (13.3)	10 (34.5)	6.349	0.012
Preoperative radiotherapy	16 (10.7)	7 (24.1)	2.827	0.093
History of hypertension	53 (35.3)	12 (41.4)	0.384	0.535
Diabetes mellitus	22 (14.7)	7 (24.1)	0.984	0.321
Coronary artery disease	24 (16.0)	2 (6.9)	0.972	0.324
Peripheral vascular lesions of the lower extremities	11 (7.3)	5 (17.2)	1.840	0.175
History of previous abdominal surgery	41 (27.3)	6 (20.7)	0.554	0.457
History of recent aspirin use	22 (14.7)	3 (10.3)	0.104	0.747
Smoking history	26 (17.3)	6 (20.7)	0.186	0.666
Alcohol consumption history	20 (13.3)	3 (10.3)	0.019	0.891
Preoperative hypoproteinemia	17 (11.3)	5 (17.2)	0.334	0.563
Preoperative anemia	13 (8.7)	5 (17.2)	1.141	0.285
Pelvic effusion	48 (32.0)	8 (27.6)	0.220	0.639
Clinical stage			1.383	0.240
0/I/II	95 (63.3)	15 (51.7)
III/IV	55 (36.7)	14 (48.3)
Tumour T stage			0.030	0.863
Tis/T1/T2	49 (32.7)	9 (31.0)
T3/T4	101 (67.3)	20 (69.0)
N stage			0.390	0.532
N-	87 (58.0)	15 (51.7)
N+	63 (42.0)	14 (48.3)
Degree of tumour differentiation			4.003	0.144
Medium differentiation	124 (82.7)	22 (75.9)
High differentiation	17 (11.3)	2 (6.9)
Low differentiation	9 (6.0)	5 (17.2)
Mucinous adenocarcinoma	14 (9.3)	7 (24.1)	3.813	0.051
Vascular invasion	38 (25.3)	7 (24.1)	0.018	0.892
Nerve invasion	75 (50.0)	22 (75.9)	6.548	0.011
Preoperative fever of ≥ 37 °C	31 (20.7)	10 (34.5)	2.627	0.105
ASA grading			0.283	0.595
I/II	112 (74.7)	23 (79.3)
III/IV	38 (25.3)	6 (20.7)
Tumour height			69.652	< 0.001
Upper rectum	55 (36.7)	1 (3.4)
Middle rectum	73 (48.6)	2 (6.9)
Lower rectum	22 (14.7)	26 (89.7)
Maximum transverse tumour diameter (cm)	3.5 (2.8, 4.6)	3.8 (3.2, 4.4)	0.502	0.616
CEA (ng/mL)	3.25 (1.60, 10.55)	5.79 (3.21, 10.41)	2.444	0.015
CA19-9 (ng/mL)	13.65 (8.02, 21.43)	21.61 (12.28, 24.80)	2.299	0.022
ALB (g/L)	38.0 ± 4.1	38.0 ± 3.8	0.001	0.999
GLU (mmol/L)	4.89 (4.35, 5.63)	5.24 (4.61, 5.33)	0.849	0.396
Potassium (mmol/L)	3.9 (3.7, 4.2)	3.9 (3.8, 4.2)	0.527	0.598
PT-T (second)	12.3 (11.6, 12.9)	12.3 (11.7, 12.6)	0.031	0.975
DD (mg/L)	0.77 (0.62, 1.11)	0.88 (0.72, 1.72)	1.874	0.061
WBC (109/L)	5.38 (4.54, 6.41)	5.75 (5.07, 5.82)	1.106	0.269
PLT (109/L)	203 (166, 239)	204 (188, 222)	0.672	0.502

BMI: Body mass index; TNM: Tumour-node-metastasis; ASA: American Society of Anaesthesiologists; CEA: Carcinoembryonic antigen; ALB: Albumin; GLU: Glucose level; PT-T: Prothrombin time; DD: D-dimer levels; WBC: White blood cell count; PLT: Platelet count.

Logistic regression analysis of sphincter preservation in laparoscopic radical RC surgery

To evaluate whether the factors that differed significantly between the sphincter-preserved and sphincter-unpreserved groups were significant risk factors for sphincter preservation in laparoscopic radical RC surgery, logistic regression analyses were conducted. Sphincter preservation was used as the dependent variable (0 = unpreserved sphincter, 1 = preserved sphincter), while variables with significant differences (P < 0.1) in Table 1 were included as independent variables. The results indicated that the presence of colonic polyps, mucinous adenocarcinoma, nerve invasion, and tumour height were independent risk factors influencing sphincter preservation in laparoscopic radical RC surgery (P < 0.05; Table 2).

Table 2 Logistic regression analysis of sphincter preservation in laparoscopic radical rectal cancer surgery.

Variable	β	P value	OR	95%CI
Residence	-1.046	0.131	0.351	0.090-1.367
Colonic polyps	-2.207	0.006	0.110	0.023-0.535
Neoadjuvant chemotherapy	1.848	0.302	6.347	0.190-211.759
Preoperative radiotherapy	0.807	0.674	2.241	0.052-95.916
Mucinous adenocarcinoma	2.504	0.009	12.230	1.847-80.999
Nerve invasion	1.836	0.012	6.272	1.499-26.247
Tumour height
Upper rectum			Refence
Middle rectum	-0.301	0.837	0.740	0.042-13.001
Lower rectum	5.292	< 0.001	198.820	13.665-2892.686
CEA	0.021	0.390	1.021	0.974-1.070
CA19-9	0.015	0.240	1.015	0.990-1.041
DD	0.013	0.755	1.013	0.934-1.099

TNM: Tumour-node-metastasis; CEA: Carcinoembryonic antigen; DD: D-dimer levels; OR: Odds ratio; CA19-9: Carbohydrate antigen 19-9.

DISCUSSION

RC accounts for approximately one-third of all colorectal cancer (CRC) cases, which is the third most common cancer worldwide[6]. Early detection followed by surgical resection significantly improves survival outcomes for patients with RC[7]. Laparoscopic surgery has become an increasingly preferred minimally invasive approach for treating RC, with radical resection remaining the cornerstone of therapy[8]. Advances in preoperative neoadjuvant therapies, laparoscopic techniques, and the adoption of the principles of total mesenteric excision and circumferential resection margin have demonstrated that a distal resection margin of 1 cm does not compromise oncologic safety in RC[9]. These advancements have contributed to a higher rate of sphincter-preserved surgeries and low anastomoses[10-12]. More patients are now undergoing sphincter-preserving procedures with colorectal or coloanal anastomoses, offering the potential benefit of avoiding a permanent stoma. Improvements in surgical techniques and adjuvant therapies have reduced the frequency of abdominoperineal resections (APRs), supporting minimally invasive surgery and the restoration of gastrointestinal continuity[13,14]. A low stoma rate is considered an indicator of high surgical quality. Permanent colostomies not only alter the original anatomy of the colon but also disrupt bowel continuity, necessitate lifelong stoma care, and negatively impact the patient's body image and quality of life[15]. The current surgical focus is on preserving function while achieving radical tumour resection, with efforts aimed at avoiding permanent stomas whenever possible. This study attempts to determine whether other factors besides the distance of the lower tumor margin from the anal verge and the invasion of the anal canal by cancerous tissue affect sphincter preservation, exploring risk factors that may influence sphincter preservation.

The relationship between tumour height and sphincter preservation has been critically evaluated[16]. A smaller distance between the tumour and the anal verge, as well as a low tumour location, significantly increases the risk of sphincter removal in patients with RC. These factors heighten the likelihood of tumour invasion into the anal canal and the spread of cancerous tissue to the sphincter. In such cases, APR is often chosen to ensure complete resection, minimise postoperative recurrence, and achieve the goals of surgery[17]. However, the decision to perform sphincter-preserving surgery rather than APR involves careful consideration of multiple factors. These include the response of the tumour to radiotherapy, the feasibility of achieving complete tumour clearance, the patient's functional status and comorbidities[18]. Advances in surgical anastomoses and the use of neoadjuvant radiochemotherapy have improved the rates of sphincter preservation in cases of low and intermediate RC[19]. In selected patients, partial intersphincter resection can avoid radical colostomy, although its oncological outcomes remain controversial[20]. Despite these advancements, a significant number of patients with RC still face challenges related to unsuccessful sphincter preservation. Notably, there is a lack of studies that specifically identify potential factors influencing laparoscopic sphincter preservation during radical resection. Previous studies have suggested that neoadjuvant therapy might impair anorectal function; however, for patients with very low RC, neoadjuvant therapy could reduce tumour size, decrease the need for excessive bowel resection, and increase the likelihood of sphincter preservation[21]. The German RC Trial further highlighted that sphincter preservation was more frequent in patients who received preoperative radiotherapy, implying that tumour shrinkage plays a crucial role in avoiding permanent colostomy. It remains unclear whether neoadjuvant therapy directly enhances the chances of sphincter preservation or simply influences the surgeon's inclination to perform such procedures[22].

Nerve invasion refers to the pathological phenomenon where tumour cells infiltrate neural structures and spread along the nerve sheath. It is categorised by the extent of tumour involvement, including invasion of the nerve lining, neuronal sheath, and nerve tunica albuginea, or tumour cells encircling at least one-third of the nerve tunica albuginea layer[23,24]. The identification of nerve invasion is based on microscopic examination of biopsy specimens by pathologists. Nerve invasion serves as a significant pathological indicator and prognostic factor in patients with RC. Patients with nerve invasion typically exhibit decreased overall survival, increased local recurrence, and increased metastatic disease[25]. This pathological feature is associated with more advanced disease RC nerve invasion. Preoperative prediction of nerve invasion status could help in personalising treatment strategies. Recent studies suggest that clinical imaging histology models based on preoperative magnetic resonance imaging (MRI) radiomic features combined with clinical risk factors can noninvasively predict nerve invasion, enabling tailored treatment approaches for patients with RC. Nerve invasion is not limited to tumour cell infiltration and growth along neural pathways; it also involves interactions between tumour cells and neurotrophic and chemokine factors released from the surrounding microenvironment. These interactions contribute to tumour invasion, local recurrence, and metastasis, leading to a poorer prognosis[26,27]. However, the influence of nerves and nerve signals on the tumour microenvironment remains poorly understood, and the role of neurogenesis in CRC remains unclear. In this study, nerve invasion was associated with a lower likelihood of sphincter preservation. Therefore, RC patients with nerve invasion might benefit from more aggressive preoperative interventions.

Rectal mucinous adenocarcinoma is a histological subtype of RC that accounts for 5%-15% of RC cases. It is characterised by the presence of abundant extracellular mucin within the tumour, constituting over 50% of the adenocarcinoma tumour stroma, as determined through histopathological examination[28]. Mucinous tumours exhibit distinct molecular features compared to non-mucinous tumours and can be reliably identified by T2-weighted MRI, which highlights the large, high-signal pools of mucin. This subtype is associated with an abnormal molecular background and aggressive biological behaviour, making patients more susceptible to metastasis and local recurrence. Compared to non-mucinous rectal adenocarcinomas, mucinous adenocarcinomas present a higher risk of local recurrence and reduced overall survival. While adjuvant chemotherapy for patients undergoing radical surgery might improve patient survival rates[29], mucinous adenocarcinomas often demonstrate resistance to neoadjuvant chemotherapy, resulting in treatment failure. This resistance is attributed to the physical barrier created by mucin and the hypoxic environment, both of which reduce the efficacy of chemoradiotherapy. Studies focusing on the molecular differences between mucinous and non-mucinous adenocarcinomas could pave the way for the development of tailored chemotherapeutic agents for this subgroup of patients[30-32]. Improving outcomes for patients with mucinous adenocarcinomas necessitates a more individualised approach to therapy. This includes optimising neoadjuvant treatment regimens, implementing more effective preoperative adjuvant chemotherapy, and intensifying treatment for patients with associated risk factors. These strategies aim to reduce the likelihood of sphincter preservation failure.

Colonic polyps are defined as masses protruding into the lumen of the colon, with their histological classification primarily distinguishing between neoplastic and non-neoplastic polyps[33]. Non-neoplastic polyps, which are not associated with developmental abnormalities, include hyperplastic, juvenile, inflammatory, and dysmorphic lesions. Conversely, adenomatous polyps are precancerous lesions whose identification and removal could prevent the onset of CRC. Colonoscopy, often combined with endoscopic mucosal resection, is a safe and highly effective method for diagnosing, treating, and monitoring rectal lesions. Colonoscopy and polypectomy are effective preventive methods for managing precancerous lesions and reducing CRC-related mortality[34,35]. In this study, patients who underwent sphincter-preserving surgery had more comorbid colonic polyps. Adenoma progression typically occurs gradually, allowing diagnostic studies to play a critical role in early detection. Through endoscopic and imaging techniques, new heterochronous rectal tumours can be identified early, including asymptomatic lesions. This enables timely radical resection with sphincter preservation in cases where RC remains in situ, minimising the risk for radical surgeries. Future analytical studies should focus on further understanding the aetiology and pathogenesis of RC in patients with coexisting colonic polyps that have a wide range of genetics, environmental exposures, and associated factors that may modulate disease risk[36].

Treatment options for patients with RC, particularly those with low RC, have become increasingly complex. For patients with tumours that are easily resectable, preoperative radiotherapy might be used to achieve a complete clinical response, a controversial approach known as nonoperative treatment or deferred surgery[37]. Although laparoscopic surgery offers the advantage of magnified visualization, the surgical maneuver is more challenging. Surgeons must navigate risks such as incomplete tumour resection, poor anastomotic blood supply, and inadvertent sphincter injury, all of which may lead to sphincter preservation failure. Therefore, these complex procedures should be performed by highly experienced colorectal surgeons[38,39]. This study is the first to analyse potential risk factors affecting sphincter preservation in laparoscopic radical RC surgery, offering valuable insights for preoperative assessment, targeted interventions, and patient monitoring. Despite the importance of these factors, studies examining their impact on sphincter preservation in RC surgery remain limited.

This study has several limitations. First, as a retrospective analysis, it is inherently susceptible to selection bias and the influence of unmeasured confounders. Second, this study was conducted at a single centre, which might limit the generalisability of the findings to the broader patient population. Third, the analysis of risk factors did not encompass all potential factors that could impact sphincter preservation in laparoscopic surgery. To address these limitations, future research should include larger sample sizes and prospective, multicentre cohort studies to provide more comprehensive and generalisable insights.

CONCLUSION

Several risk factors were identified in patients with RC that influence successful tumour resection and sphincter preservation. These findings can aid in identifying high-risk patients, enabling targeted preoperative assessments and interventions. Addressing these risk factors through targeted interventions might help minimise the risk of sphincter damage during radical surgery. Further investigation is needed to better understand the influence of preoperative factors on sphincter preservation in patients with RC. In conclusion, this study identified independent risk factors affecting sphincter preservation in laparoscopic radical RC surgery, including nerve invasion, mucinous adenocarcinoma, colonic polyps, and tumour height. Evaluation of these risk factors could enhance the awareness of sphincter preservation and improve surgical outcomes in patients with RC.