Establishment of a prediction model of postoperative infection complications in patients with gastric cancer and its impact on prognosis
Highlight box
Key findings
• Age >65 years, preoperative anemia, albumin <30 g/L, and gastrointestinal obstruction were risk factors of postoperative infection in patients with gastric cancer (P<0.05).
What is known and what is new?
• Patients with gastric cancer have a higher incidence of postoperatively infection complications.
• This model can effectively identify patients with high-risk gastric cancer and postoperative infection.
What is the implication, and what should change now?
• Strengthening interventions in patients at high risk of postoperative infection may be beneficial in reducing the incidence of infection complications and ultimately improving patient outcomes.
Introduction
Gastric cancer is one of the most common malignant tumors of the digestive tract, second only to colorectal cancer (1). Surgery is the main treatment of gastric cancer, but the incidence of postoperative infection complications is high. One retrospectively clinical study showed that the incidence of postoperative infection complications in patients with gastric cancer was as high as 6.8% (2), another reported a higher incidence of 12.6% (3), and still another reported a postoperative lung infection rate as high as 14.7% (4). Current studies have confirmed that postoperative infection is associated with lower long-term overall survival in patients with gastric cancer (2,5,6). Therefore, the prevention and treatment of postoperative infection in patients with gastric cancer is a difficult but crucial challenge. The key to preventing postoperative infection is to identify high-risk factors and high-risk patients for postoperative infection in gastric cancer, and a small number of researchers have discussed the relevant factors of postoperative infection in this patient group. In one study, overweight status was shown to be a risk factor for incision infection after radical gastric resection (7). It was also found that patients with hypertension, combined organ resection, history of abdominal surgery, and long duration of surgery were more likely to develop intra-abdominal infection (8). Different research indicated that myopenia, tumor size, pathology, and multiple organ resection were independent contributing factors to intra-abdominal infection (9). Moreover, it has been reported that open surgery, chronic obstructive pulmonary disease, intraoperative blood transfusion, and long operation time were risk factors of postoperative lung infection in patients with gastric cancer (10). However, the ability of individual biological indicators to identify patients with gastric cancer at high-risk for postoperative infection is limited. We thus aimed to develop and evaluated a nomogram-based prediction model capable of identifying those patients with gastric cancer at high risk of postoperative infection. We present this article in accordance with the TRIPOD reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-231/rc).
Methods
General information
From January 2014 to December 2017, we retrospectively collected the data from 571 patients with gastric cancer admitted to the Affiliated People’s Hospital of Ningbo University, and the patients were divided into an infection group (n=81) and control group (n=490) according to whether or not the patients experienced infection after surgery. The inclusion criteria were the following: (I) gastric cancer, (II) surgical treatment in the Affiliated People’s Hospital of Ningbo University, (III) age ≥18 years old, and (IV) completed data available. Meanwhile, the exclusion criteria were the following: (I) gastric stromal tumor, (II) infectious diseases before surgery, (III) presence of other malignant tumors, (IV) remote metastasis required multi-visceral resections, and (V) loss of patient in follow-up. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by Ethics Committee of the Affiliated People’s Hospital of Ningbo University (No. 202200147) and individual consent for this retrospective analysis was waived.
Treatment
All patients completed the related examinations. After contraindications to surgery were considered, radical gastrectomy for gastric cancer (mainly including radical distal gastrectomy, radical gastrectomy, and total gastrectomy) was performed. Preventive antibiotic treatment was given at 30 minutes before the surgery (prophylactic antibiotic use time was 48 hours). After surgery, symptomatic supportive treatment, such as early ambulation and maintaining the water-electrolyte balance, was given. When the patient's gastrointestinal function was restored, the diet was gradually resumed. After surgery, according to the pathological results, the postoperative adjuvant treatment plan was decided.
Data collection
Information related to age, sex, body mass index, smoking history, history of alcoholism, hypertension, diabetes, hyperlipidemia, preoperative anemia, blood transfusion, serum albumin, preoperative gastrointestinal obstruction, lesion size, surgical method, surgical resection range, dissected lymph node count, lymph node metastasis, tumor cell differentiation, operation time, intraoperative blood loss, and mortality rate at 5 years after surgery was collected. Postoperative follow-up was carried out via outpatient visits at least once a year for 5 years.
Statistical analysis
SPSS2 6.0 software (IBM Corp.) was used to complete the data analysis, and a P value <0.05 was considered to be statistically significant (2-tailed). The measurement data of the 2 groups were expressed as mean ± standard deviation, with the differences between the 2 groups being analyzed with the independent samples t test. The count data of the 2 groups are expressed as numbers and percentages, with the chi-squared test being used to analyze the differences between the 2 groups. Multivariate regression was used to analyze risk factors of postoperative infection complications in patients with gastric cancer. R 4.0.3 statistical software (The R Foundation for Statistical Computing) was used to establish a prediction model for postoperative infection complications in patients with gastric cancer.
Results
Comparison of clinical features between the 2 groups
The flowchart of patients with gastric cancer included is shown in Figure 1. There were statistically significant differences in age, diabetes, preoperative anemia, preoperative albumin, preoperative gastrointestinal obstruction, and surgical method between the 2 groups (P<0.05). Compared with that in the control group, the mortality rate at 5 years after surgery was significantly increased in the infection group (39.51% vs. 26.12%; P=0.013; Table 1).
Table 1
| Variable | Infection group (n=81) | Control group (n=490) | t/χ2 value | P value |
|---|---|---|---|---|
| Age (years) | 3.395 | 0.065 | ||
| Mean ± SD | 64.80±8.79 | 60.32±10.24 | 3.721 | 0.000 |
| >65 years | 36 (44.44) | 166 (33.88) | ||
| ≤65 years | 45 (55.56) | 324 (66.12) | ||
| Gender | 0.397 | 0.529 | ||
| Male | 48 (59.26) | 272 (55.51) | ||
| Female | 33 (40.74) | 218 (44.49) | ||
| Body mass index (kg/m2) | 25.73±3.85 | 25.24±3.69 | 1.101 | 0.271 |
| History of smoking | 6 (7.41) | 32 (6.53) | 0.086 | 0.768 |
| History of alcoholism | 3 (3.70) | 15 (3.06) | 0.094 | 0.759 |
| Hypertension | 5 (6.17) | 34 (6.94) | 0.064 | 0.800 |
| Diabetes | 10 (12.35) | 17 (3.47) | 12.157 | 0.000 |
| Hyperlipidemia | 12 (14.81) | 67 (13.67) | 0.076 | 0.783 |
| Preoperative anemia | 8 (9.88) | 13 (2.65) | 10.238 | 0.001 |
| Blood transfusion | 4 (4.94%) | 11 (2.24%) | 1.971 | 0.160 |
| Preoperative albumin (g/L) | 42.469 | 0.000 | ||
| Mean ± SD | 31.96±5.30 | 36.64±4.89 | 7.880 | 0.000 |
| <30 g/L | 28 (34.57) | 43 (8.78) | ||
| ≥30 g/L | 53 (65.43) | 447 (91.22) | ||
| Preoperative gastrointestinal obstruction | 10 (12.35) | 20 (4.08) | 9.536 | 0.002 |
| Surgical method | 4.532 | 0.033 | ||
| Open surgery | 4 (4.94) | 7 (1.43) | ||
| Minimally invasive surgery | 77 (95.06) | 483 (98.57) | ||
| Surgical resection range | 2.587 | 0.274 | ||
| Radical distal gastrectomy | 32 (39.51) | 155 (31.63) | ||
| Proximal radical gastric resection | 12 (14.81) | 65 (13.27) | ||
| Total gastrectomy | 37 (45.68) | 270 (55.10) | ||
| Dissected lymph node count | 20.47±3.85 | 20.92±3.92 | 0.959 | 0.338 |
| Lymph node metastases | 37 (45.68) | 211 (43.06) | 0.194 | 0.660 |
| Tumor cell differentiation | 0.051 | 0.822 | ||
| Poorly differentiated or undifferentiated | 12 (14.81) | 68 (13.88) | ||
| Medium to high differentiation | 69 (85.19) | 422 (86.12) | ||
| Lesion size (cm) | 4.12±2.10 | 4.39±2.09 | 1.074 | 0.283 |
| Duration of surgery (min) | 204.28±27.89 | 201.61±28.74 | 0.778 | 0.437 |
| Amount of intraoperative bleeding (mL) | 165.91±60.49 | 172.04±58.49 | 0.869 | 0.385 |
| Mortality at 5 years postoperatively | 32 (39.51) | 128 (26.12) | 6.173 | 0.013 |
Data are shown as n (%) or mean ± standard deviation.
Risk factors for postoperative infection in patients with gastric cancer
Multivariate logistics regression analysis showed that age >65 years, preoperative anemia, albumin <30 g/L, and gastrointestinal obstruction were risk factors of postoperative infection in patients with gastric cancer (P<0.05; Table 2).
Table 2
| Variables | B value | Standard error | Wald value | P value | Relative risk (95% CI) |
|---|---|---|---|---|---|
| Age >65 years | 0.567 | 0.263 | 4.641 | 0.031 | 1.763 (1.052–2.954) |
| Diabetes | 0.836 | 0.490 | 2.909 | 0.088 | 2.306 (0.883–6.025) |
| Preoperative anemia | 1.452 | 0.499 | 8.465 | 0.004 | 4.272 (1.606–11.360) |
| Albumin <30 g/L | 1.778 | 0.302 | 34.677 | 0.000 | 5.919 (3.275–10.696) |
| Gastrointestinal obstruction | 1.362 | 0.448 | 9.239 | 0.002 | 3.902 (1.622–9.389) |
| Open surgery | 0.839 | 0.771 | 1.184 | 0.276 | 2.315 (0.511–10.498) |
| Constant | −11.035 | 2.278 | 23.473 | 0.000 | 0.000 |
The value of age in predicting postoperative infection in patients with gastric cancer
Age was valuable in predicting the postoperative infection in patients with gastric cancer, and the area under the curve was 0.620 (95% confidence interval: 0.560–0.679; P=0.030; Figure 2).
The value of albumin in predicting the absence of postoperative infection in patients with gastric cancer
Albumin exhibited value in predicting the absence of postoperative infection in patients with gastric cancer, and the area under the curve was 0.736 (95% confidence interval: 0.676–0.795; P<0.001; Figure 3).
Establishment and validation of a postoperative infection complication prediction model for patients with gastric cancer
The R 4.0.3 statistical software was used to randomly divide the dataset into a training set and validation set. The sample size of the training set was 286, and the sample size of the validation set was 285. In terms of the predictive model's value in predicting postoperative infection in patients with gastric cancer, the area under the receiver operating characteristic (ROC) curve in the training set was 0.788 (95% confidence interval: 0.711–0.864), and the area under the ROC curve in the validation set was 0.779 (95% confidence interval: 0.703–0.855). In the validation set, the model was evaluated with the Hosmer-Lemeshow goodness-of-fit test, resulting in a chi-squared value of 5.589 and a P value of 0.693 (Figures 4-7).
Types of postoperative infection complications in patients with gastric cancer
Postoperative infection in patients with gastric cancer mainly included lung infection, abdominal infection, and incision infection (Table 3).
Table 3
| Variable | Value, n (%) |
|---|---|
| Abdominal infection | 28 (34.57) |
| Incision infection | 13 (16.05) |
| Lung infections | 38 (46.91) |
| Urinary tract infections | 2 (2.47) |
Discussion
Surgery is one of the main methods for treating gastric cancer, but the infection rate after surgery is high, and the main infection sites include the abdomen, incision, and lung, among others. Postoperative infection can lead to delayed postoperative adjuvant therapy. Moreover, infection will lead to further immune dysfunction, so it may lead to the poor prognosis of patients, and current studies have confirmed that postoperative infection is associated with reduced postoperative survival (2). The present study also showed there to be a significant increase in mortality at 5 years in the infection group. Therefore, the prevention and treatment of postoperative infection in patients with gastric cancer is a challenging but crucial issue. In this study, the factors related to postoperative infection in patients with gastric cancer were examined. It was found that age >65 years, preoperative anemia, albumin <30 g/L, and gastrointestinal obstruction were risk factors for postoperative infection in patients with gastric cancer (P<0.05).
Gastric cancer is more likely to occur in middle-aged and older adult individuals. In older adult patients, the body's immune function decreases and the susceptibility to bacteria increases. Moreover, older adult patients are more likely to develop pneumonitis, so increasing age is a risk factor of postoperative infection (11,12), which is consistent with the results of the present study. In the state of anemia, the blood flow to all organs in the body is insufficient, and surgery will further aggravate the anemic state, resulting in a decrease in immune function. At the same time, anemia leads to delayed healing of the incision and anastomosis, causing an increased risk of infection (13). Albumin is the most important protein in human plasma and is synthesized by the liver. Albumin is an important nutrient in the human body and can maintain plasma osmolality and reflect the nutritional status of the body, with studies confirming decreased albumin to be a risk factor of postoperative infection (14-16). Gastrointestinal obstruction refers to a narrowing or atresia that occurs anywhere from the mouth to the anus, either alone or in combination with other structural malformations. There are many causes of gastrointestinal obstruction. Patients with gastrointestinal obstruction may have abdominal distension, abdominal pain, nausea, vomiting, and other symptoms, and gastrointestinal obstruction can lead to gastrointestinal edema, increased gastrointestinal permeability, and ultimately abdominal infection (17,18). Preoperative correction of these risk factors may be beneficial to reducing the risk of postoperative infection in patients with gastric cancer, ultimately improving patient outcomes.
Furthermore, in order to better identify patients with gastric cancer at high risk of postoperative infection, we established a nomogram prediction model based on the relevant risk factors. This predictive model could intuitively reflect the risk of postoperative infection in patients with gastric cancer. A study in patients with gastric cancer also showed that the predictive nomogram model could better assess the risk of postoperative lung infection (10). The predictive nomogram model established in the present study exhibited good value in predicting postoperative infection in patients with gastric cancer. Strengthening the intervention in such high-risk patients may be beneficial to reducing the rate of postoperative infection rate in these patients and improving prognosis.
Limitations
The number of patients with infection was relatively low. Therefore, we failed to study the complications according to the Clavien-Dindo III-IV complications. And due to the limitations of this retrospective study, we failed to study some data in the present study.
Conclusions
At present, the relevant biological indicators of the prognosis of various diseases are the focus of researches (13,19). The present study found that the incidence of postoperative infection complications in patients with gastric cancer was high, and our model could effectively identify patients with gastric cancer at high risk of postoperative infection.
Acknowledgments
Funding: None.
Footnote
Reporting Checklist: The authors have completed the TRIPOD reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-231/rc
Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-231/dss
Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-231/prf
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-231/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by Ethics Committee of the Affiliated People’s Hospital of Ningbo University (No. 202200147) and individual consent for this retrospective analysis was waived.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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(English Language Editor: J. Gray)
