Published online Jan 15, 2019. doi: 10.4251/wjgo.v11.i1.39
Peer-review started: September 18, 2018
First decision: October 18, 2018
Revised: October 29, 2018
Accepted: December 4, 2018
Article in press: December 5, 2018
Published online: January 15, 2019
Several staging systems and various serum markers have been investigated to provide prognostic information, including the tumor, node and metastasis staging system, margin-positive resection, lymph node metastasis, multifocal disease, an elevated carbohydrate antigen 19-9 level, and vascular involvement. Some combined indexes of clinical characteristics and laboratory biomarkers have also been demonstrated to be prognostic factors, such as the platelet to albumin ratio, neutrophil-to-lymphocyte ratio and albumin to gamma-glutamyltransferase ratio. However, the albumin-to-alkaline phosphatase ratio (AAPR), which is a novel prognostic factor for hepatocellular carcinoma (HCC), has not yet been studied in cholangiocarcinoma (CCA).
The AAPR has been recently revealed as a prognostic index for HCC, whereas its role in CCA remains unclear.
To clarify the prognostic value of the preoperative blood AAPR in patients undergoing surgery for CCA. The results may be of interest to CCA researchers and of help to clinicians aiming to develop a means to prevent the development of CCA. Besides, serum albumin levels and alkaline phosphatase levels are both simple but differentiated and objective variables, which are more easily applied in clinical practice.
We conducted a retrospective cohort study that included 303 patients with histologically confirmed CCA from Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Using the patients’ informatics database of Peking Union Medical College Hospital, we compiled a list of all patients who had been diagnosed with CCA between 2002 and 2014. The patients who had undergone a primary attempt at curative resection and whose diagnoses were confirmed by pathological examination were involved in this study. Curative resection was defined as complete macroscopic removal of the tumor and was performed in 156 patients (51.5%). The AAPR of all the patients in this study was calculated on the basis of preoperative blood value. Univariate analysis in overall survival (OS) and recurrence-free survival (RFS) was performed using the Cox proportional hazards model. The OS was evaluated in all 303 patients, and the RFS was evaluated in the 156 patients who underwent curative resection. The primary endpoint was OS, which was calculated from the date of surgery to the date of cholangiocarcinoma-associated death. The secondary endpoint was RFS, which was calculated from the date of surgery to the date of recurrence. The most appropriate cut-off values of AAPR were determined by receiver operating characteristic curve. Baseline characteristics were compared using Chi-squared test or Fisher’s exact test. Survival data were calculated using the Kaplan-Meier method and were compared using the log-rank test. Univariate and multivariate survival analyses were conducted using the Cox proportional hazards regression methodology.
The overall 1-, 3-, and 5-year survival rates were 70.2%, 38.0%, and 16.5% in the low (< 0.41) AAPR group and 81.7%, 53.9%, and 33.4% in the high (≥ 0.41) AAPR group, which was a significant difference (P < 0.0001). The median OS (95%CI) and RFS (95%CI) in the AAPR ≥ 0.41 group were 48.5 mo (40.5-56.4) and 39.2 mo (31.1-47.3), respectively. In the AAPR < 0.41 group, the median OS (95%CI) and RFS (95%CI) were 30.3 mo (21.3-39.3) and 18.5 mo (11.1-25.8), respectively. The recurrence-free survival rate was significantly higher in the high AAPR group than in the low AAPR group (P = 0.017). The main limitation of this study is its single-center and retrospective design. More prospective studies and basic research are still needed to further elucidate the molecular mechanism of AAPR related to prognosis.
In this study, we focused exclusively on the prognostic value of the AAPR in patients with CCA receiving surgery. This is the first study focusing on validating the prognostic potential of AAPR in patients with CCA receiving surgery. Its results may be of interest to CCA researchers and of help to clinicians aiming to develop a means to prevent the development of CCA. Albumin and alkaline phosphatase are both simple but differentiated and objective variables, which are more easily applied in clinical practice. Moreover, this study investigated the relationship between AAPR and other clinical factors. The present study indicated that low AAPR level, large tumor size, multiple tumors, and advanced clinical stage were identified as significant predictors of poor prognosis. To our knowledge, this is the first study to analyze the correlation between the AAPR and CCA. The results indicate that the AAPR is an independent prognostic indicator for patients with CCA; patients with an AAPR less than 0.41 exhibited inferior OS and RFS. Both univariate analysis and multivariate analysis showed that an AAPR less than 0.41 is associated with poor prognosis. A low AAPR may reflect the patient’s malnutrition status, suppressed immunity, and relatively severe disease condition, such as liver or bone metastasis.
Our present study suggested that AAPR is a potentially valuable prognostic index in patients with CCA receiving surgery. In view of its low cost, usability and prognostic power, AAPR should be included in the design of future clinical trials and research projects. A lack of validation cohorts limits the further confirmation of AAPR as an independent indicator for CCA patients. Larger scale and multi-center research is still warranted for further confirmation.