Patient data analysis
During the study period, a total of 174 patients with AC underwent radical pancreatoduodenectomy, including 2 patients diagnosed with ampullary neuroendocrine tumors, 3 patients died of accidents, 1 patient died within 30 days after surgery, and 6 patients were excluded due to incomplete information or lost to follow-up, so a total of 162 patients with ampullary cancer were enrolled. Among them, the chief complaints included 67 cases of jaundice, 53 cases of upper abdominal discomfort, 11 cases of fever, 11 cases of loss of appetite, 8 cases of urine yellow, 4 cases of nausea and anorexia, 5 cases of tumors found by examination, 1 case of waist and back discomfort, 1 case of skin pruritus, 1 case of emaciation. Among 138 jaundice patients, 38 patients received preoperative jaundice reduction treatment, including 12 patients received Endoscopic Retrograde Cholangiao-Pancreatography, Endoscopic sphincterotomy, Endoscopic Nasal Bile Drainage (ERCP + EST + ENBD) jaundice reduction treatment, and 26 patients received Percutaneous Transhepatic Cholangial Drainage (PTCD) jaundice reduction treatment. Some patients received postoperative adjuvant therapy, but the specific therapeutic regimen was not known. The median follow-up time was 40 months [Inter-Quartile Range (IQR) = 21–58 months]. The 1-, 3-, 5-year OS and RFS were 87%, 60.5%, 44.1% and 67.9%, 54.3%, 40.6%, respectively. The specific clinicopathological features of the patients are detailed in Table 1.
Correlation Between Ca19-9/ggt And Clinicopathological Characteristics Of Patients
CA19-9/GGT was obtained by the patient's first laboratory examination after hospitalization, and its optimal cut-off value was obtained using the receiver operating characteristic (ROC) curve, which was approximately 0.14 [area under the curve (AUC) = 0.839, 95% CI: 0.779–0.899]. The corresponding sensitivity was 87.7%, and the specificity was 68.5%. Patients were divided into two groups by the optimal cut-off value of CA19-9 / GGT: low-risk group (CA19-9 / GGT ≤ 0.14, n = 69) and high-risk group (CA19-9 / GGT > 0.14, n = 93) (Table 2). Compared with the low-risk group, the high-risk group patients (CA19-9 / GGT > 0.14) were presented with more postoperative adjuvant therapy (P = 0.025), lymph node metastasis (P = 0.036), and nerve invasion (P = 0.002); lower differentiation grade(P = 0.001); higher levels of total bilirubin (P = 0.011) and CA19-9 (P < 0.001) and more advanced TNM stage (P < 0.001).
Ca19-9/ggt Is A Significant Prognostic Indicator
Receiver operating characteristic (ROC) curve was used to calculate optimal cutoff values for predictors. Cox regression model was used for survival analysis of risk factors (Table 1). In univariate analysis, gender (P = 0.023), tumor size (P = 0.023), differentiation extent (P = 0.023), lymph node metastasis (P = 0.004), nerve invasion (P = 0.001), AJCC 8th edition TNM stage (P < 0.001), total bilirubin (P < 0.001), CA19-9 (P < 0.001), PLR (P = 0.027), GPR (P = 0.008), GLR (P = 0.004), AGR (P = 0.003), CA19-9/GGT (P < 0.001) were identified as risk factors for OS (Table 1); gender (P = 0.027), tumor size (P = 0.002), differentiation extent (P < 0.001), lymph node metastasis (P < 0.001), nerve invasion (P = 0.004), AJCC 8th edition TNM staging (P < 0.001), total bilirubin (P < 0.001), CA19-9 (P < 0.001), GPR (P = 0.011), GLR (P = 0.003), AGR (P = 0.005), CA19-9/GGT (P < 0.001) affected postoperative recurrence-free time (RFS) (Table 1).
In multivariate analysis, the independent risk factors affecting OS were CA19-9/GGT (P = 0.001, HR = 2.459, 95% CI : 1.450–4.167), medium / low differentiation (P < 0.001, HR = 6.372, 95% CI : 1.470–27.610), AGR (P < 0.001, HR = 6.474, 95% CI : 2.972–13.850), CA19-9 (P < 0.001, HR = 3.401, 95% CI : 1.953–5.922) ; the independent risk factors affecting RFS included CA19-9/GGT (P = 0.002, HR = 2.333, 95%CI : 1.371–3.971), medium / low differentiation (P < 0.001, HR = 4.760, 95%CI : 1.077–21.030), lymph node metastasis (P = 0.022, HR = 1.762, 95%CI : 1.089–2.849), CA19-9 (P < 0.001, HR = 3.477, 95% CI : 1.991–6.073), AGR (P < 0.001, HR = 5.582, 95% CI : 2.576–12.093). CA19-9/GGT > 0.14 was significantly correlated with poor prognosis of OS (P < 0.001) and RFS (P < 0.001) (Fig. 1).
Performance Comparison Of Ca19-9/ggt And Other Prognostic Indicators
CA19-9/GGT, other inflammation-based scores, routine laboratory parameters and AJCC 8th staging system were used to evaluate the predictive ability by the concordance index (C-index) (Table 3). Compared with other prediction parameters, CA19-9/GGT had the highest C-index for OS and RFS prediction, which was 0.753 ( 95% CI : 0.748–0.838 ) and 0.745 ( 95% CI : 0.737–0.827 ), respectively. In terms of prediction accuracy, CA19-9/GGT was significantly superior to other inflammatory scores and CA19-9 in OS and RFS prediction.
Prognostic Nomograms Integrating Ca19-9/ggt And The Ajcc 8th Tnm Staging Systems
A new Nomogram prediction model was constructed by combining the AJCC 8th TNM staging system with CA19-9/GGT (Fig. 2). The C-index derived from the traditional AJCC 8th staging system and the Nomogram prediction model has been entered in Table 3. Compared with AJCC 8th TNM staging system(OS: C-index = 0.759, 95%CI = 0.632–0.785; RFS: C-index = 0.772, 95%CI = 0.659–0.805), the C-index of Nomogram prediction model in OS ༈C-index = 0.787, 95%CI = 0.685–0.712༉and RFS༈C-index = 0.795, 95%CI = 0.696–0.713) elevated.
The calibration curve intuitively reflected that the 1-year, 3-year, and 5-year OS and RFS of the actual observations were in good consistency with the 1-year, 3-year, 5-year OS and RFS calculated by the Nomogram prediction model (Fig. 3). Decision curve analysis (DCA), as an assessment method reflecting the clinical net benefit of the predictive model, intuitively confirms that the Nomogram predictive model involved a wider range of threshold probabilities than the traditional AJCC 8th staging system, yielded better net benefit, thereby provided higher prediction accuracy (Fig. 4, Table 4).