Clinical value of measuring plasma D-dimer levels in patients with esophageal cancer

General information

We selected 120 patients with esophageal cancer (esophageal cancer group) who were admitted to our department for surgical treatment from June 2020 to May 2022, including 70 men and 50 women aged 48–79 years (mean, 65.8 ± 7.10 years).

During the same period, 60 healthy participants (control group) were selected from the physical examination department, including 37 men and 23 women aged 46–88 years (mean, 65.7 ± 7.53 years).

The inclusion criteria for the esophageal cancer group were pathological evidence of malignancy (excluding small cell carcinoma)—established based on electronic gastroscope biopsy—and the absence of prior radiotherapy, chemotherapy, and/or immunotherapy.

The exclusion criteria for this study included preoperative use of aspirin, clopidogrel, low molecular weight heparin, and other drugs that affect coagulation and fibrinolysis; inability to undergo radical surgical resection; esophageal cancer combined with pulmonary embolism, deep vein thrombosis, coronary heart disease, diabetes, liver cirrhosis, cerebral embolism, or other hypercoagulable diseases; and esophageal cancer combined with other malignant tumors.

Among the 120 patients with esophageal cancer, 18 had upper thoracic esophageal cancer, 58 had middle thoracic esophageal cancer, 36 had lower thoracic esophageal cancer, and 8 had cancer of the esophagogastric junction. Upper thoracic and middle thoracic esophageal cancers were treated with thoracic laparoscopy combined with lower three-field esophagectomy. Lower thoracic esophageal and esophagogastric junction cancers were treated with thoracic laparoscopy combined with lower two-field esophagectomy. Following postoperative pathological diagnosis, all esophageal cancers were classified as squamous cell carcinomas, while all esophagogastric junction cancers were classified as adenocarcinomas. The postoperative pathological staging of each tumor was determined according to the 2009 standards of the International Union Against Cancer and the American Joint Committee on Cancer, showing 10 cases of stage IA, 24 of stage IB, 12 of stage IIA, 18 of stage IIB, 20 of stage IIIA, 24 of stage IIIB, and 12 of stage IVA. Among these cases, 38 were classified as well differentiated, 44 as moderately differentiated, and 38 as poorly differentiated.

Patients whose postoperative pathology showed positive lymph node metastasis received chemotherapy. The chemotherapy regimen used for squamous cell carcinoma was the following: paclitaxel 150 mg/m2 intravenously infused on day 1 + cisplatin 50 mg/m2 intravenously infused on day 1, then every 2 weeks, for a total of 4 times. For adenocarcinoma, the chemotherapy regimen was the following: capecitabine 1000 mg orally bid days 1–14 + oxaliplatin 130 mg/m2 intravenously on day 1, then once every 3 weeks, for a total of 4 times.

D-dimer detection method

Morning blood samples were collected from patients with esophageal cancer prior to the operation and on days 1 and 14 after the operation. A single fasting morning venous blood sample (3 mL) was collected from each healthy participant using a 3-mL vacuum blood collection tube. The anticoagulant reagent 3.8% sodium citrate (100 mL/bottle, Shanghai Enzyme Biotechnology Co., Ltd., No. 5500, Yuanjiang Road, Minhang District, Shanghai) was added to the blood at a ratio of 1:9. Each sample was centrifuged after collection at 168 g for 10 min; the temperature during centrifugation was 2–8℃. After the plasma was separated, the test was carried out within 2 h. An automatic latex-enhanced immunoassay was used to detect the plasma D-dimer content in the specimens from the two groups. The normal range of D-dimer concentration is 0–0.5 µg/mL. A positive D-dimer test was defined as having a D-dimer concentration > 0.5 µg/mL.

Follow-up care

Postoperative follow-up methods for patients with esophageal cancer were implemented as follows: In the first year after surgery, follow-up was conducted in the outpatient clinic every 3 months, and every 6 months thereafter for 2–3 years. Follow-up included peripheral plasma D-dimer measurements, blood cell analysis, a full set of routine biochemistry tests, direct enhancement of neck, chest, liver, gallbladder, and pancreas by computed tomography, and whole-body bone scans.

Statistical methods

SPSS 18.0 software (IBM Corp., Armonk, New York, USA) was used for data analysis. Quantitative data were subjected to analysis of variance. The Mann–Whitney U test was performed for quantitative data that did not meet the normality standard, while a t-test was performed for quantitative data that met the normality standard. Among the qualitative data, unordered multi-category data were analyzed using the chi-square test. The 3-year survival rate in patients with esophageal cancer was calculated using the Kaplan–Meier method. Related factors affecting the 3-year survival rate in patients with esophageal cancer were analyzed using logistic multivariate analysis. Receiver operating characteristic curves were prepared to determine the accuracy of plasma D-dimer in predicting esophageal cancer outcomes. The area under the curve (AUC) was used to estimate the diagnostic accuracy. Statistical significance was determined at P < 0.05.

Ethics statement

All participants provided informed consent and the study protocol was approved by the hospital ethics committee (approval number: Puyuan Fuyilun [2,023,040]). This study was performed in accordance with the criteria of the Declaration of Helsinki.

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