Published online Aug 7, 2018. doi: 10.3748/wjg.v24.i29.3281
Peer-review started: April 20, 2018
First decision: June 6, 2018
Revised: June 16, 2018
Accepted: June 27, 2018
Article in press: June 27, 2018
Published online: August 7, 2018
Although gallbladder cancer (GBC) is a relatively rare hepato-biliary malignancy with a low incidence, it is generally insidious and progresses rapidly. Most GBC patients are diagnosed at an advanced stage, losing the chance of surgical intervention, which is considered to yield an optimal therapeutic effect. Despite the great advance in surgical techniques in recent years, the prognosis remains very poor. Therefore, it is urgent to explore a clinically simple, convenient and cost-effective prognostic indicator to detect and identify high-risk patients with GBC, on whom, appropriate surgical treatment can be performed as soon as possible. In recent years, a variety of studies have shown that the increased plasma fibrinogen concentration representing coagulation function of the body and the declined plasma albumin concentration indicating nutrient state of the body are independent risk factors for poor prognosis of malignant tumor patients. Integrating the results of studies on fibrinogen-to-albumin ratio (FAR) in the prognosis of patients with esophageal cancer and breast cancer, we naturally speculate that FAR might be significantly more effective than single elevated plasma fibrinogen concentration or reduced plasma albumin concentration in predicting the prognosis of GBC patients.
Hence, the present was mainly designed to determine and verify the role of high FAR in the prognosis of surgically-treated GBC patients. We aimed to detect a simple, convenient and cost-effective prognostic biomarker for GBC patients undergoing surgical treatment, which could facilitate the selection and identification of GBC patients suitable for surgical resection for clinical surgeons. Notably, this would be beneficial to both surgeons and GBC patients. Our findings would provide clinical evidence and research directions for other large-scale, multi-center randomized controlled trials in the future.
The main objective of our study was to determine whether high preoperative FAR was an independent risk factors for postoperative survival in GBC patients. As a result, we demonstrated that high preoperative plasma FAR value and low preoperative plasma albumin concentration were independent risk factors for poor post-operative prognosis of GBC patients. In addition, the prognostic effect of high preoperative FAR value was significantly stronger than the low preoperative plasma albumin concentration. Therefore, these above-described outcomes provided not only clinical direction for further clinical validation or relevant studies, but also clinical data for further researches concerning the underlying mechanisms.
First, the present study was a clinical retrospective one. A prearranged EXCEL data collection table was utilized to collect and organize the various variables, including epidemiological data, clinicopathological characteristics, and research-related target data. Moreover, the receiver operating characteristic (ROC) curve was used to obtain the optimal cut-off values for fibrinogen, albumin, and FAR. Continuous variables in normal distribution were shown as mean ± SD, and continuous variables without normal distribution were expressed as medians (range: minimum-maximum). Categorical variables were expressed as percentages or frequencies. Variables from the EXCEL table were further imported into the SPSS 24.0 statistical software for statistical analysis. Of note, the statistical methods used in our study were different from those used in previous studies of survival analysis regarding the prognosis of cancer patients. To begin with, the ROC curve was used to identify the optimal cut-off value of fibrinogen, albumin, and FAR in this study, which was more reasonable and more scientific than the traditional methods, which used the mean value of the targeted or identified biomarkers based on previous studies. It was because the cut-off value identified by this method was significantly associated with the overall survival of the targeted population. Secondly, most of the previous studies on postoperative prognosis of GBC patients only focused on single index, such as plasma fibrinogen or plasma albumin. However, in this study, we used the plasma FAR, representing the division of high fibrinogen and low albumin, which contributed to the more significant prognostic effect of the index, and effectively inhibited the influence of confounding factors. Together, the method was more scientific and harbored higher statistical efficiency.
In this study, we demonstrated that high preoperative plasma FAR and low preoperative plasma albumin concentration were independent risk factors for poor postoperative outcome in GBC patients. To the best of our knowledge, this is the first study indicating that high preoperative plasma FAR is an unfavorable prognostic biomarker for GBC patients undergoing surgical intervention. Additionally, it also verifies the role of low preoperative plasma albumin in predicting the worse prognosis of GBC patients receiving surgery. Nevertheless, our study is a retrospective study but not a prospective study, which might lead to a systematic bias. Moreover, the sample size in our study is relatively small, and it is a single-center study, and these defects would attenuate the statistical effectiveness of our conclusions. Nevertheless, the study was conducted in China, which did not include GBC patients from other ethnic groups and countries, thereby affecting the clinical applicability and generalizability of the results. Therefore, more multiple-center, large-scale prospective studies enrolling GBC patients from different races and countries are necessary to further verify the conclusions of this study.
At present, accumulating studies have confirmed that high preoperative plasma fibrinogen concentration and low preoperative plasma albumin concentration are independent risk factors for poor prognosis of GBC patients. In addition, some studies have further validated that high preoperative plasma FAR is an independent risk factor for poor prognosis of patients with esophageal cancer and breast cancer, and its predictive ability is significantly more potent than that of single biomarkers, such as high plasma fibrinogen and low plasma albumin. Therefore, we naturally speculated that FAR, representing the body’s coagulation function and the body’s nutritional status, might be an independent risk factor for predicting postoperative adverse outcomes of GBC patients, which has been confirmed in our study. Our study was the first to reveal the prognostic effect of FAR in GBC patients, and we also used the ROC curve as a novel method to identify the optimal cut-off value for the prognostic index studied. The potential mechanism for our conclusion might be indicated as follows: fibrinogen, as a coagulation factor, was associated with the growth, progression and metastasis of cancer cells, while albumin was correlated with the nutrient status and immune function of the body. Therefore, the high preoperative plasma fibrinogen and low preoperative albumin are both unfavorable prognostic factors for GBC patients. The FAR can enhance and magnify the prognostic effect of the single index such as fibrinogen and albumin. Collectively, our research provides a simple, convenient and cost-effective prognostic indicator to help clinicians to more efficiently screen and identify high-risk GBC patients in clinical practice, and to facilitate patients to adopt better surgical methods and optimal follow-up strategy in the future.
In the present study, it is indicated that the plasma FAR, incorporating two biomarkers, harbors a significantly better prognostic impact on surgically-treated GBC patients compared to a single prognostic indicator, such as plasma albumin or plasma fibrinogen. In the future, more large-scale, multiple-center and prospective studies, including GBC patients from other races and countries, should be conducted to further investigate and verify the conclusion derived from our study. Additionally, more basic experiments exploring the potential mechanisms are also necessary in the future.