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Elderly Patients With Colorectal Cancer Surgical Curative Effect Evaluation And Colorectal Cancer Perioperative Serum Soluble Nkg2d Ligands Expressed

Posted on:2013-01-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y W ZangFull Text:PDF
GTID:1224330395950890Subject:Surgery
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The number of elder patients suffering from colorectal carcinoma has been remarkably increasing these years as a reason of population aging. Generally speaking, the body function of the elders will collapse a lot as they may have more chances to get chronic diseases such cardiovascular disease, chronic respiratory inflammation. Not only the tolerance to surgeries are poor, but also a high risk for operative complications. Many surgeons and dependents tend to choose conservative managements, and older patients cannot get the most scientific and standard treatment. It is so important to focus on the standard therapies of these people in order to increase their life span and improve life quality. It is necessary to conduct a comprehensive assessment of surgery outcomes, in order to explore more reasonable and effective treatments plans for aged colorectal cancer.ObjectiveTo evaluate surgical safety, short-term and long-term outcomes of aged colorectal patients older than75.MethodsThe clinical data of301colorectal carcinoma patients aged60years’old and older treated by operative procedures from September2007to October2010in the Department of General Surgery of Huashan Hospital affiliated to Fudan University were analyzed retrospectively. Of these,132were75years of age or older and comprise the elderly group, and the other169cases comprise the younger group. Comparisons were made between the two groups in the aspects of operative risk, operative results, short-term outcomes, thus to evaluate the safety of radical surgeries for elder patients. Between January2009to October2010,27patients (>75years) with colorectal cancer underwent laparoscopic-assisted one-stage radical operation (LAP group) in our hospital.56patients (>75years) underwent open radical operation in the same period of time (OPEN group). Perioperative characteristics and short-term outcomes were compared to investigate the safety and possibility of laparoscopic procedures in elderly patients with colorectal carcinoma. All the patients were follow-up surveyed after the operation, the relationships between various clinical indications and prognosis of colorectal carcinoma were studied. And the factors influencing the survival curve of colorectal carcinoma were selected.ResultsCompared with the younger group (60-74years), co-morbidity rate was higher in the elderly group (>75years). However, there was no significance in complication rate,30-day mortality between the two groups. Recover of bowl function was similar as well. We also found laparoscopic operation need a longer surgical time, but much shorter length of incision, reduced use of analgesics, comparing with OPEN group. Bowel function recovered earlier in LAP group. There was no statistical difference in the incidence of post operative complications. Until April30th,2011,213of all301patients were alive with no progression,18of which lived with tumor,59were dead, and the other11patients were withdrawn. The average follow-up time was34.54±0.85months. The elderly group (>75years) has an average follow-up time of32.09±1.00months. Overall3-year survival rate and disease-free survival rate were62.1%and56.9%. Meanwhile the average follow-up time of the younger group (60-74years) was36.57±1.24months. Overall3-year survival rate and disease-free survival rate were79.0%and74.5%. In univariate analysis, age was one of the significant prognostic factors. In multivariate survival analysis, complications, curative or palliative operation, and tumor staging were proved to be crucial to prognosis.ConclusionIn select individuals75years of age or older, radical surgery for primary colorectal carcinoma can be done with perioperative morbidity and mortality rates comparable to those obtained in younger individuals, while achieving excellent disease-free and overall long-term survival. Laparoscopic operation for elderly patients is quite safe and reliable, and may have advantages in terms of faster gastrointestinal recovery compared with open surgery. Natural killer cells are the major components of innate immune system, as they can directly attack the target cells without antigen sensitization. Major histocompatibility complex class I chain-related molecules (MICs) and UL16-binding proteins (ULBPs) are the two major types of specific ligands for NKG2D, which continuously expressing on the surface of tumor cells. Activated receptor NKG2D can recognize its ligands directly, transmit signals to activate NK cells, and initiate the process of immune surveillance and clearance. In the past few years, people pay more attention to the role of NKG2D ligands in viral infection and tumor invasion. A series researches have confirmed the potential significance of NKG2D/NKG2DL signaling in immune responses against tumors. With the progression of malignancies, combined NGK2DLs might be hydrolyzed by metalloproteinase into soluble form dissolving in tissue fluid. Soluble ligands decrease the antigen density on tumor cells. Moreover, they can competitively combined with NKG2D receptors, cause the endocytosis of these receptors, inhibit the activity of immune cells, and induce immune evasion.ObjectiveTo investigate the change of soluble NKG2D ligands, sMICA, sMICB, and ULBPs, in the serum of colorectal cancer patients during perioperative period.MethodsThirty-eight patients with colorectal carcinoma hospitized in Huashan Hospital Affiliated to Fudan University were enrolled in the Tumor Group. Peripheral venous blood was drawn before radical surgery and on the third day after the operation. Ten healthy person were enrolled in the Control Group, and peripheral venous blood was drawn. Serum was isolated and tested in enzyme-linked immunosorbent assay to meter the concentration of sMICA, sMICB, and ULBPs. Analyze the correlation between each soluble ligand and the biological characteristics of colorectal carcinoma. Assess the diagnosis significance of soluble NKG2D ligands.ResultsThe concentration of soluble NKG2D ligands sMICA, sMICB, and ULBPs in serum of colorectal cancer patients had positive significant correlation. sMICA in cancer patients’serum was significantly higher than in control group (P<0.05), the difference of sMICB and ULBPs were not so remarkable (P<0.1). All three tested soluble ligands maintained at the similar density on the third day after the operation compared with what before the surgery. The concentration of soluble NKG2D ligands in TNM stage Ⅲ-Ⅳ might maintain for a longer time than in stage Ⅰ-Ⅱ. Among the three soluble ligands, sMICA had the most significant correlation with the staging and metastasis of colorectal carcinoma. sMICB was correlated with metastasis, not with tumor staging. ULBPs had no relations with any clinical characteristics. sMICA correlated with serum CEA and CA19-9, area under curve is0.854. The optimal diagnostic critical value was48pg/mL, and sensitivity, specificity is97.37%,60.00%.ConclusionSoluble NKG2D ligands are increased in colorectal carcinoma patients, and maintain still in a short time postoperatively. Soluble MICA had significant correlation with tumor staging, metastasis, had a high diagnostic value, thus can serve as a reference for earlier screening for colorectal carcinoma.
Keywords/Search Tags:Aged, Colorectal carcinoma, Surgical Safety, Survival Analysis, Laparoscopic SurgeryColorectal carcinoma, Natural killer cell, NKG2D, sMICA, sMICB, ULBPs
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