Colorectal cancer (CRC) is among the most prevalent cancers worldwide and its incidence is rapidly increasing (1). Many risk factors for morbidity after CRC surgery have been reported, including patient background and surgical factors (2, 3).

Recently, a comprehensive prognostic score, the Naples prognostic score (NPS), calculated from serum albumin and total cholesterol concentrations, the lymphocyte-to-monocyte ratio (LMR), and the neutrophil-to-lymphocyte ratio (NLR), has been reported to be a powerful prognostic index for CRC complications (4). A previous study reported that a high NPS was associated with postoperative morbidity after rectal cancer surgery (5). However, the impact on short-term outcomes of surgical strategies was not investigated.

Minimally invasive colectomy (MIC) is less invasive than open colectomy (OC) (6) and may improve short-term outcomes in patients with high NPS. Thus, the current study aimed to retrospectively evaluate the effects of the NPS on postoperative outcomes after OC and MIC.

Patients. This retrospective cohort study included 256 consecutive patients who underwent curative surgery for CRC at the Department of Surgery of the Miyazaki Prefectural Nobeoka Hospital between January 2013 and March 2020. The inclusion criteria were as follows: 1) pathologically-confirmed adenocarcinoma, 2) diagnosis of clinical stages I-III colorectal cancer, and 3) curative surgery. The exclusion criteria were as follows: 1) pathological stage IV disease and 2) missing data on clinicopathological characteristics. OC and MIC were performed in 139 and 117 patients, respectively. We further divided each OC and MIC group into two subgroups depending on whether the NPS was high or low. Short-term outcomes between patients with high- and low-NPS were compared in the OC and MIC groups using our institutional database. The ethics committee of our hospital approved the study procedure and waived the requirement for written informed consent (Registry Number 20190830-3).

Naples prognostic score definitions. The NPS was defined based on the following four parameters: serum albumin level, total cholesterol level, LMR, and NLR. As previously reported by Galizia et al., the cutoff values were 4 mg/dl for serum albumin, 180 mg/dl for total cholesterol, 2.96 for NLR, and 4.44 for LMR (4). Patients with serum albumin, total cholesterol or LMR lower than the thresholds got one point; otherwise, they got zero. Patients with an NLR higher than 2.96 got one point, while those with a lower NLR got zero. The sum of the scores for each parameter comprised the NPS score. Patients were categorized into three groups according to the NPS: patients with an NPS of 0 were assigned to group 1, patients with an NPS of 1 or 2 to group 2, and patients with an NPS of 3 or 4 to group 3 (Table I). Patients with NPS 1 and 2 were defined as the low-NPS group and those with NPS score 3 as the high-NPS group.

Treatment strategy. Lower alimentary canal endoscopy and thoracoabdominal computed tomography (CT) were routinely performed to determine the clinical stage before colectomy. The pathological findings were defined according to the tumor, node, metastasis classification (American Joint Committee on Cancer Staging Manual, 8th edition). The treatment strategy and follow-up evaluation were performed according to the 2019 Japanese Society for Cancer of the Colon and Rectum guidelines 2019 (7). Primary resection with lymph node dissection was recommended for stages I-III CRC. MIC was defined as laparoscopic colectomy. Morbidity was defined as a Clavien–Dindo classification (CDc) ≥II (8). Severe morbidity was defined as a CDc ≥IIIb, requiring endoscopic, radiological, or surgical intervention under general anesthesia.

Statistical methods. All data analyses were performed using JMP® software version 13.1 (SAS Institute, Cary, NC, USA). The clinicopathological characteristics and laboratory data of the two groups were compared using the chi-square test for categorical variables and the Mann–Whitney U-test for continuous variables. Statistical significance was set at p<0.05. Logistic regression analysis was performed to estimate the hazard ratio (HR) with a 95% confidence interval (CI) for postoperative complication (CDc ≥II and IIIb). The following clinical factors were adopted as risk factors for overall survival (OS): age at colectomy (≥70 vs. <70 years), sex (male vs. female), body mass index (≥25 vs. <25 kg/m²), NPS (high-NPS vs. low-NPS), tumor location (right-sided vs. left-sided), American Society of Anesthesiologists physical status (3 vs. 1, 2), pathological stage (stage III vs. stage 0, I, II), and comorbidity with diabetes mellitus (present vs. absent). We selected factors with a p-value ≤0.1 for subsequent multivariate analysis, and variables with a p-value <0.05 were recognized as independent risk factors.

Clinical features of patients who underwent open colectomy. Table II shows the characteristics of patients who underwent OC, depending on whether the NPS was high or low. No significant differences were observed between high- and low-NPS groups.

Short-term outcomes after open colectomy. Table III demonstrates the short-term outcomes after OC, depending on whether the NPS was high or low. The high-NPS groups had significantly higher incidences of postoperative morbidities compared with the low-NPS groups after OC (Clavien-Dindo classification (CDc) ≥II; p=0.022, CDc ≥IIIb; p=0.036). Furthermore, patients with high NPS experienced significantly more frequent reoperations after OC (p=0.0052).

Risk factors for any postoperative morbidities (CDc ≥II) after open colectomy. Table IV shows the results of the univariate and multivariate analyses of risk factors for postoperative morbidities (CDc ≥II) after OC. Multivariate analysis demonstrated that high-NPS was an independent risk factor for postoperative morbidities (CDc ≥II) after OC (HR=2.40; 95%CI=1.121-5.181; p=0.024).

Risk factors for severe postoperative morbidities (CDc ≥IIIb) after open colectomy. Table V shows the results of the univariate and multivariate analyses of risk factors for severe postoperative morbidities (CDc ≥IIIb) after OC. Multivariate analysis demonstrated that high-NPS was an independent risk factor for severe postoperative morbidities (CDc ≥IIIb) after OC (HR=4.19; 95%CI=1.052-20.619; p=0.042).

Clinical features of patients who underwent minimally invasive colectomy. Table VI shows the characteristics of patients who underwent MIC, depending on whether the NPS was high or low. High-NPS was significantly correlated with older age than those in the low-NPS groups. In addition, the high NPS group showed a trend toward a lower body mass index, which was not statistically significant.

Short-term outcomes after minimally invasive colectomy. Table VII shows the short-term outcomes after MIC depending on whether the NPS score was high or low. No significant differences were observed in operative time, bleeding, or postoperative morbidities after MIC.

In this study, we demonstrated that a high NPS was an independent risk factor for postoperative morbidity after OC, but not after MIC.

The NPS is an inflammation-based prognostic score developed as a marker for CRC by Galizia et al. (4). The NPS includes factors that reflect nutritional status (albumin and total cholesterol) and inflammation (NLR and LMR), and has emerged as a novel prognostic marker for various types of cancer, such as colorectal (4, 9, 10), lung (11), esophageal (12), and hepatocellular (13). Recently, a high NPS was a risk factor for oncological postoperative morbidity. Hosoda et al. reported that high-NPS was associated with postoperative morbidity (CDc ≥III) after liver resection for hepatocellular carcinoma (14). Galizia et al. reported that a high NPS significantly correlated with postoperative morbidity after gastrectomy for gastric cancer (15). Recently, high-NPS was reported to lead to postoperative morbidity (CDc ≥III) after colectomy for rectal cancer (5). However, to the best of our knowledge, no study has elucidated the superiority of MIC over OC for postoperative morbidity in patients with CRC with a high NPS.

OC is generally considered to be more invasive than MIC. Serum interleukin (IL)-6 and IL-10 levels after OC, which are commonly used to assess surgical stress, were significantly higher than those after MIC (6, 16). In addition, C-reactive protein levels (CRP) after OC were also significantly higher than those after MIC (6, 17, 18). McSorley et al. demonstrated that the magnitude of the postoperative systemic inflammatory response, as evidenced by CRP levels, was significantly associated with complications after CRC surgery (19). NPS is valuable in predicting postoperative complications because it serves as an indicator of inflammation, malnutrition, and immunosuppression (14). The higher invasiveness of OC compared to MIC might increase postoperative complications in patients with CRC with a high NPS.

Previous studies reported that high-NPS was correlated with severe postoperative morbidity (CDc ≥III) after hepatectomy for hepatocellular carcinoma (14) and colectomy for rectal cancer (5). Furthermore, a large cohort study showed that a high NPS was significantly associated with mortality and reoperation in patients undergoing colectomy for diverticulitis (20). It also suggested a correlation between the NPS and severity of complications after colectomy for diverticulitis (20). In the present study, high-NPS was significantly associated with severe postoperative morbidity (CDc ≥IIIb) and reoperation after OC. Four cases of reoperation after OC (none after MIC) were noted, and the reasons were two anastomotic leakages, one abdominal dehiscence, and one postoperative bleeding. High NPS may lead to more severe complications after surgery because of increased inflammation, malnutrition, and immunosuppression.

The lower invasiveness of MIC could yield various advantages during colectomy. A large cohort study demonstrated that MIC contributed to fewer postoperative complications than OC, specifically surgical site infections, urinary tract infections, and pneumonia (21). A recent retrospective study investigating 69,418 colectomies from the Japanese Diagnosis Procedure Combination database suggested that MIC could contribute to decreasing the postoperative mortality rate, surgical morbidity rate, and postoperative length of stay (22). In addition, a randomized controlled trial showed that MIC was associated with a lower incidence of long-term complications and a better quality of life in the first 12 months after surgery than OC (23). Furthermore, a multi-center cohort analysis revealed that the postoperative complication rate was lower in the MIC group compared to the OC group (24). In the current study, a novel advantage was suggested: MIC may not increase postoperative morbidity, even in patients with a high NPS.

Study limitations. First, this was a single-center, retrospective study. Second, this study did not include robotic surgeries.

A high NPS was associated with postoperative complications after OC, but not after MIC. The reduced invasiveness of MIC may contribute to lower postoperative morbidity in patients with a high NPS.

The Authors declare that they have no conflicts of interest in relation to this study.

T Yamane wrote the manuscript. K Doi developed the study concept and design. T Kaida, Y Suzuki, F Kitamjura and H Ishiodori collected the clinical data. S. Honda conducted critical revision of manuscript. M Iwatsuki coordinated the study, oversaw collection and analysis of the results. All Authors discussed the data and commented on the manuscript.

The Authors thank all the people who contributed to this work.

There was no financial support for this research.

No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.