| Gallbladder cancer is considered as the most common biliary malignant tumor with an incidence rate increasing year by year, accounting for 2% of all biliary tract surgical procedures. The cause of gallbladder cancer is not known and the associated risk factors include age, gender, race, diet, hormone, bacterial infection, obesity, diabetes, gallstone, gallbladder adenomyosis, polypoid adenoma and etc. Gallbladder cancer is an aggressive malignancy with a tendency of fast growth and early metastasis, and a dismal prognosis as well. According to AJCC staging system-based statistics from the US National Cancer Data Base, the median survival time of patients with stage IB gallbladder cancer is less then two years, and that of stage Ⅱ no longer than one year; the five-year survival rates of stage ⅡA and ⅡB are 7% and 9% respectively, while that of stage Ⅲ and Ⅳ only 3% and 2%. The epidemiological data of gallbladder cancer in China indicates that postoperative 5-year survival rates of patients with stage 0, Ⅰ, Ⅱ, Ⅲ, IVA and IVB gallbladder cancer are 100%.58.7%,40.2%,13.5%,9.2% and 7.1% respectively. Although imageology and molecular biology have gained a rapid development in recent years, the diagnosis and treatment level of gallbladder cancer did not improve significantly.The treatment options for patients with gallbladder cancer are surgery, chemotherapy, radiotherapy, interventional therapy, targeted therapy and etc. Surgery is a preferred method of treating gallbladder cancer at present. The method chosen depends upon tumor stage and where the tumor arises. It is generally acknowledged that based on the TNM staging system, a simple cholecystectomy to remove the gallbladder is usually all that is needed for stage Ⅰ gallbladder cancer; standard radical operation for stage Ⅱ; people now still have unanimous opinions about whether to operate extended radical resection on patients with stage Ⅲ and Ⅳ gallbladder cancer since the tumor has invaded adjacent organs. The extended radical resection is an option for eligible patients with stage Ⅲ, while palliative resection for patients with stage Ⅲ and Ⅳ who have lost the best possible chances of having operation. Curative resection is the only way to improve prognosis of gallbladder cancer nowadays. As gallbladder cancer is sensitive to radiotherapy, radiation therapy can be a supplement to surgical treatment. The chemotherapy for gallbladder cancer has a poor effect without approved treatment solutions. Fluorouracil, doxorubicin, mitomycin and nitrosoureas are widely applied to chemotherapeutic regimens for gallbladder cancer. In recent years, gemcitabine, platinum and capecitabine have achieved some good results in chemotherapy for gallbladder cancer, meaning that chemotherapy could extend the lifetime of some patients with advanced gallbladder cancer. Chemotherapy with selective intra-arterial infusion is a regional interventional chemotherapy through intranperative intra-arterial. intubation or postoperative arterial cannula, and could be effective for patients with advanced gallbladder cancer. As chemotherapy and radiotherapy have limited-effects, targeted therapy is becoming the focus of research on gallbladder cancer treatment. The current clinical studies have confirmed the functions of EGFR, MARK access and vascularization in tumorigenesis. The application of erlotinib, sorafenib, bevacizumab, cetuximab in treating patients with advanced-stage and metastatic gallbladder cancer can be found.The prognosis of gallbladder cancer can be affected by a variety of factors. From the angle of work of clinical pathology, the factors include the stages of gallbladder cancer, lymphatic metastasis, depth of invasion, tumor differentiation and etc. From the angle of work of epidemic diseases, it has been verified that inflammation was closely associated with gallbladder cancer, having a key role in initiating, maintaining and promoting tumor growth, and it is suggested that inflammation might affect the prognosis of gallbladder cancer. From the angle of work of immunology, the changes in immune state of tumor microenvironment are closely related to the development and progression of tumors, and could be considered as an important factor with the prognosis. It can be helpful for accurately predicting prognosis to know the factors associated with prognosis of gallbladder cancer from multi-perspectives, so as to provide important reference for clinical treatment. The objective of this study is to find the factors associated with prognosis of gallbladder cancer from the angles of clinical pathology, systemic inflammatory under epidemic diseases and tumor microenvironment under immunology based on retrospective analysis, in order to offer a better guidance for clinical treatment. Based on this, the content included three parts:Part I Relationships between clinicopathological characteristics and prognosis in patients with gallbladder carcinomaPurposeThe objective of this study was to evaluate the relationships between clinicopathological characteristics and prognosis in patients with gallbladder carcinoma (GBC).Materials and MethodsFrom 2001 to 2013,145 patients with GBC were recruited in this retrospective study. The correlation of clinical data with median overall survival period of patients was analyzed by univariate survival analysis. The multivariate prognosis analysis was performed to select the independent prognostic factors.Results1. The univariate analysis showed that level of total bilirubin, level of CEA, level of CA19-9, level of CRP, albumin, hemoglobin, operation mode, operation margin, pathological types, histologic differentiation,T (depth),N (lymphonodus), M (metastasis),TNM stage and Nevin stage significantly correlated with the prognosis of the patients(p<0.05).2. The results of the multivariate analysis(Cox regression)showed Nevin stage, operation mode and hemoglobin were independent prognostic factor for the patients with gallbladder cancer.ConclusionNevin stage,operation mode and hemoglobin were independent prognostic factor for the patients with gallbladder cancer. Therefore, early diagnosis and radical surgery are greatly needed to improve the prognosis of gallbladder cancer.Part Ⅱ Prognostic significance of preoperative neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in patients with gallbladder carcinomaPurposeNeutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were-immune response-related indicators. Preoperative NLR and PLR had been considered to be related to the prognosis of various cancers. The objective of this study was to evaluate the prognostic significance of NLR and PLR in patients with gallbladder carcinoma (GBC).Materials and MethodsFrom 2001 to 2013,145 patients with GBC were recruited in this retrospective study. Cutoff values of NLR and PLR were determined by receiver operating characteristic curves (ROC). The correlation of clinical data, including tumor differentiation, nevin stage, TNM stage, operation margin, operation mode, NLR, PLR, hemoglobin, C reactive protein (CRP), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) with median survival period of patients was analyzed by univariate survival analysis. The multivariate prognosis analysis was performed to select the independent prognostic factors.ResultsThe cutoff values of NLR and PLR were 1.94 and 113.33 respectively. Compared with low NLR and low PLR group, the 5-year survival rates in high NLR and high PLR group were reduced (P<0.05).The degree of tumor differentiation, nevin stage, TNM stage, operation mode, NLR, PLR, CA199, total bilirubin, CRP and CEA were associated with the median survival period of patients (P<0.01).The multivariate prognosis analysis showed that NLR, nevin stage, operation mode and hemoglobin were independent prognostic factors (P< 0.05).ConclusionPreoperative NLR and PLR were closely related to prognosis of patients with GBC, and might be useful for the evaluation of prognosis of patients with GBC.Part Ⅲ Relationships between tumour-infiltrating immune cells, clinicopathological characteristics and survival in patients with gallbladder carcinomaPurposeThe interactions between tumour cells and immune cells in gallbladder carcinoma (GBC)have not been systematically investigated. In the current study, we explored the relationship between tumour-infiltrating immune cells and the clinicopathological features of GBC. Furthermore, we investigated the prognostic value of tumour-infiltrating immune cells.Materials and MethodsThe levels of the immune markers CD3, CD8, CD45RO, CD15 and CD68 were analysed by immunohistochemistry, and the relationships between these markers and the clinical and histopathologic features of GBC and patient outcome were evaluated.ResultsThe density of CD3+cells was significantly related to TNM stage. The density of CD3+cells progressively decreased with the loss of histological differentiation, and this difference was significant (P<0.05). Low CD3 and high CD 15 levels were associated with shorter overall survival. A multivariate analysis showed that the combination of low CD3 expression and high CD 15 expression in tumour-infiltrating cells was an independent indicator of poor prognosis in GBC.ConclusionThe current results indicate that the combination of low CD3 expression and high CD15 expression in tumour-infiltrating cells is a novel, independent prognostic factor in patients with GBC. |
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