Two-port four-port laparoscopic resection for colorectal cancer: Efficacy and outcomes.

INTRODUCTION
Colorectal cancer (CRC) is a fatal and multifactorial tumor disease. Sedentary lifestyles, smoking, obesity, spicy diet, alcohol abuse, and other factors may increase the risk of CRC[1,2]. As the third most common tumor globally, CRC is likely to occur in high-income countries, such as Europe, North America, and Australia, while presenting a low risk in low-income countries[3]. The pathological mechanism of CRC is related to mucosal inflammation. Continuous inflammation on epithelial proliferation can easily induce cancerization. Moreover, abnormal conditions, such as oxidative damage and DNA double-strand breaks, can further increase the risk of carcinogenesis[4]. Laparoscopic surgery is a curative treatment for CRC. Compared with open surgery, it reduces bleeding, promotes recovery, and reduces complications[5]. Traditional laparoscopic surgery in patients with CRC often requires placing 4 and 5 surgical ports, which may cause concurrent wound infection and greater damage to organs, hindering therapeutic effects[6,7]. The single-port technique often has limited clinical applications because of increased operative complexity, small surgical field of view, and prolonged operation time[8]. Thus, the two-port laparoscopic approach was developed based on a single-port to widen the operating field and reduce surgical complexity[9]. However, few relevant studies and reports have investigated its application to patients with CRC.
Based on the above background, this study attempted to evaluate the clinical effects of two-port in comparison with four-port laparoscopic surgery for CRC from a multidimensional perspective to provide new insights to optimize the surgical outcomes of patients with CRC. The results are clinically significant to further improve the medical experience of these patients.

MATERIALS AND METHODS

Study population
From March 2022 to March 2025, 150 patients with CRC admitted to the study hospital were selected. The patients were divided according to the treatment method: (1) 80 patients who underwent two-port laparoscopic resection for CRC (two-port group); and (2) 70 patients who received four-port laparoscopic surgical treatment (four-port group). The sample size calculation did not rely on precalculated statistical power but was based on selecting eligible patients with CRC treated between March 2022 and March 2025.

Case selection and exclusion parameters
The eligibility requirements were as follows: (1) Diagnosis of CRC[10]; (2) Age 18-80 years; (3) Stage I-III disease[11]; (4) First-time surgical candidates for laparoscopic radical surgery; and (5) Complete medical data.
The exclusion criteria were as follows: (1) Other malignancies; (2) Recent endocrine, chemotherapy, or radiotherapy treatment; (3) Severe immunosuppressive status; (4) Abdominal operation history; (5) Organic (cardiac, cerebral, pulmonary, hepatic, or renal) diseases; (6) Peritonitis, intestinal obstruction, or perforation; (7) Cognitive/communicative defects; and (8) American Association of Anesthesiologists score > III[12].

Treatment methods
Patients in the two-port group underwent two-port laparoscopic radical resection for CRC. Briefly, patients were placed in the lithotomy position, and general anesthesia was administered via endotracheal intubation. Following routine disinfection and dressing, a 2-3 cm incision was made on the left side of the patient’s navel. The skin and tissues were incised, which served as the auxiliary operation port. An artificial CO2 pneumoperitoneum was established, and a Trocar was inserted approximately two fingers’ width from the anterior superior iliac spine on the right side, which served as the main operation port. After visualizing the lesion with the laparoscope, the tumor was resected: The right pararectal sulcus was incised, revealing the left Toldt, which was expanded. The inferior mesenteric artery lymph nodes were cleared, and a ligature was applied approximately 1 cm from the root of the ligament. The ligament of the inferior mesenteric vein was expanded outward at the same level. The sigmoid colon was freed, ensuring protection of the ureters and pelvic nerve plexus. Subsequently, the retrorectal, lateral, and anterior spaces were dissected. After the tumor was removed, the intestinal tube was disconnected to complete the resection. The resected tissue was placed in a specimen bag. The incision was sutured to achieve hemostasis, a drainage tube was then placed, and the abdominal cavity was closed.
The four-port group underwent four-port laparoscopic surgery as follows: Patients were placed in the lithotomy position, and general anesthesia was induced through tracheal intubation. A 100-mm Trocar was inserted at the upper edge of the navel as the main observation port. The location of the main operation port was the same as that in the two-port group. A secondary operation port was placed on the right side, and the assistant operation port was located at the midpoint of the line connecting the navel and the left anterior superior iliac spine. An auxiliary incision measuring 6-8 cm was made in the middle of the lower part of the umbilicus. Subsequent procedures, including specimen extraction, drainage tube placement, and intestinal anastomosis, were performed identically to the two-port technique.

Endpoints

Operative measures: This included surgical duration, intraoperative hemorrhage volume, and cumulative incision length in each cohort.

Postoperative recovery: This included the time to first flatus, ambulation initiation, and hospital stay duration.

Complications: Patients were monitored for ileus, anastomotic fistula, surgical site infection (SSI), postoperative bleeding, uroschesis, and intraperitoneal abscess, with their frequency rates computed.

Gastrointestinal function markers: Specifically, 5-mL fasting venous blood was obtained during morning hours before surgical intervention and after a 30-day recovery. Centrifuged serum specimens were subjected to radioimmunological determination of gastrin (GAS) and motilin (MT) concentrations.

Oncological biomarkers: Serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (Cyfra 21-1), and carbohydrate antigen 125 (CA125) were assessed using automated immunoassay systems before surgery and 1 month after surgery.

Humoral immunity: Preoperative and postoperative (1 month) serum immunoglobulin (Ig) A/G/M measurements were performed by turbidimetric immunoassay.

Statistical analysis
In this study, quantitative data deviating from a normal distribution are expressed as the median (interquartile range) [M(Q1, Q3)]. Normally distributed quantitative data are presented as mean ± SD. Between-group differences for quantitative variables were examined through independent t-tests, whereas within-group changes (e.g., preoperative vs postoperative measurements) were analyzed using paired t-tests. Categorical variables, summarized as n (%), were subjected to χ² tests to determine group differences. IBM SPSS Statistics version 5.0 facilitated all computations, with significance indicated by P < 0.05.

RESULTS

Patient demographics
The intergroup comparison (Table 1) showed comparable baseline patient features (e.g., sex, age, body mass index, tumor, node, metastasis stage, lesion location, and tumor diameter; P > 0.05).

Operative measure comparison
The two groups were comparable with respect to surgical duration and intraoperative hemorrhage volume (P > 0.05). However, the two-port group exhibited a smaller cumulative incision length than the four-port group (P < 0.001; Table 2).

Postoperative recovery
The two-port group had shorter time to first flatus/ambulation and shorter hospital stays than the four-port group (P < 0.001; Table 3).

Complications

Table 4 summarizes the postoperative complication rates. The rates of ileus, anastomotic fistula, SSI, postoperative bleeding, uroschesis, and intraperitoneal abscess were lower in the two-port group than in the four-port group (P = 0.019).

Gastrointestinal function markers
The preoperative values for all gastrointestinal (GI) function markers (GAS and MT) were comparable across the study groups (P > 0.05; Figure 1). Postoperatively, all values decreased markedly (all P < 0.001); however, the two-port approach maintained superior GAS and MT concentrations relative to the four-port technique (all P < 0.001).

Serum oncological biomarkers of the two patient groups

Figure 2 demonstrates comparable preoperative concentrations of CEA, Cyfra 21-1, and CA125 between the two cohorts (P > 0.05). Following surgery, both groups demonstrated significant decreases in all tumor markers (all P < 0.001), with the two-port approach showing superior reduction in CEA (P = 0.004), Cyfra 21-1 (P < 0.001), and CA125 (P < 0.001) concentrations relative to the four-port technique.

Humoral immunity
Before surgery, IgA, IgG, and IgM measurements did not differ significantly between the groups (P > 0.05). The two-port group had higher postoperative Ig levels than the four-port group (P < 0.001; Figure 3).

DISCUSSION
CRC has high late diagnosis and mortality rates, with considerable geographical differences in the risk of onset and death. Moreover, CRC tends to become more prevalent among younger people in developed countries[13,14]. To prevent and treat CRC and optimize related management, this study tried to compare and analyze the clinical effects of two surgical techniques and seek better solutions for laparoscopic surgical therapy for patients with CRC.
Initially, no significant intergroup variations were found in surgical duration and intraoperative bleeding; however, cumulative incision length was markedly reduced in the two-port group. This finding highlights the advantages of the two-port technique in achieving smaller incisions. Gu et al[15] did not find a significant difference in the operation time and blood loss volume between the single-incision and multi-port laparoscopic surgery for patients with CRC, similar to the results of the present study. Kim et al[16] also did not observe a significant difference in the operation time and intraoperative blood loss between the two-port and four-port laparoscopic techniques in patients undergoing ovarian cystectomy, aligning with our findings.
Moreover, time to first flatus/ambulation and overall hospitalization durations were shorter with the two-port approach, indicating enhanced postoperative recovery. In the study of Jiang et al[17], the two-port laparoscopic approach for patients with sigmoid colon cancer and upper rectal cancer resulted in a shorter total incision length than the four-port laparoscopic approach. This approach also facilitated a shorter time to first ambulation, exhaust, defecation, and liquid diet, which complements the results of this study.
Furthermore, significant reductions were observed in the overall complications (ileus, anastomotic fistula, SSI, postoperative bleeding, uroschesis, and intraperitoneal abscess) in the two-port group. In the study by Wang et al[18], single-incision plus single-port surgery was found to have certain clinical safety and minimally invasive characteristics when applied to patients with colon cancer, supporting the results of the present study. Additionally, Angulo et al[19] reported the higher effectiveness of the two-port than the four-port laparoscopic approach for radical cystectomy in reducing postoperative pain. This finding provides another potential clinical advantage for the clinical application of two-port laparoscopic surgery in CRC.
The postoperative levels of GAS and MT of the two-port group significantly decreased, but were still markedly higher than those in the four-port group, suggesting that the two-port group offered better protection of GI function. GAS and MT, both GI hormones, are closely related to the GI function of patients with CRC undergoing surgery, and can indicate whether patients experienced surgery-related stress[20]. Past evidence revealed markedly downregulated GAS and MT levels in patients with CRC following laparoscopic radical surgery. Hence, higher postoperative GAS and MT levels are indicative of relatively lesser surgical trauma and better GI function recovery[21], which is consistent with the outcomes of the two-port laparoscopic surgeries in the present study. The marked decreases in postoperative CEA, Cyfra21-1, and CA125 levels in the two-port group, lower than those in the four-port group, suggest that the two-port laparoscopic approach is more effective in preventing the progression of CRC. In previous studies, CEA has been shown as a reliable predictor of recurrence and clinical outcomes of laparoscopic radical surgery for CRC. Cyfa 21-1 is the most sensitive biological indicator of patients with recurrent CRC and is closely related to Dukes’ staging. CA125 shows a close connection with CRC outcomes. All three are strongly linked to CRC development[22-24].
The notable postoperative increases in IgA, IgG, and IgM expression in the two-port group in comparison with those in the four-port group support the former’s better performance in enhancing humoral immunity. In patients with CRC, short-term postoperative intervention with abdominal surgery may lead to weakened cellular immune function because of surgical trauma and stress. As patients’ condition improves and GI function enhances, their humoral immune function usually recovers well 1 month after surgery, which is similar to the results of Xu et al[25] and Bohne et al[26].
Several limitations should be noted. First, given the lack of sleep/life quality and adverse mood evaluations, supplementary analyses in these areas can help elucidate the potential advantages of two-port laparoscopic radical resection in CRC. Second, long-term patient outcomes (5-10 years) should be tracked to understand the lasting effects of the two approaches. Finally, a health economic analysis of the two approaches is necessary for the clinical promotion of the two-port technique. These deficiencies will be addressed in future research.

CONCLUSION
The results reveal that for CRC treatment, the two-port laparoscopic radical resection has more clinical merits than the four-port approach. It stands out particularly in shortening the cumulative incision length, boosting postoperative recovery, lowering the total complication rate, safeguarding patients’ GI and humoral immune functions, and curbing disease progression.