發(fā)布時間：2018-05-03 16:02

  本文選題：乳腺癌 + 凝血�。� 參考：《山東大學》2015年碩士論文

【摘要】：背景：通過不斷的研究,人們逐漸認識到腫瘤和凝血系統(tǒng)之間的相互關(guān)系在乳腺癌進展的過程中的作用。事實上,凝血系統(tǒng)的各個部分,包括血小板、凝血酶原系統(tǒng)、和纖溶系統(tǒng),均影響了許多已知的乳腺癌進展過程。術(shù)前,乳腺癌患者的凝血系統(tǒng)已經(jīng)發(fā)生了變化。在患者中,原癌基因的激活和局部微環(huán)境的缺氧能促進組織因子的過度表達,激活凝血系統(tǒng),引發(fā)體內(nèi)凝血因子改變,導致血栓。因此,較良性患者,乳腺癌患者術(shù)前有可能出現(xiàn)凝血方面的改變,同時手術(shù)創(chuàng)傷也可以造成人體凝血系統(tǒng)發(fā)生改變,引發(fā)血栓的形成。乳腺癌患者術(shù)后引起凝血系統(tǒng)如何改變,目前尚不明確。乳腺癌患者術(shù)后可出現(xiàn)下肢靜脈栓塞、肺栓塞等并發(fā)癥。一旦這些并發(fā)癥發(fā)生,都會對患者的身心和經(jīng)濟造成一定的壓力,延長患者住院時間,造成不必要的經(jīng)濟花銷,嚴重者甚至威脅到患者的生命。本文旨在探索乳腺癌患者術(shù)后凝血系統(tǒng)的改變。目的：1.探索乳腺癌患者手術(shù)前后凝血變化。2.乳腺癌患者手術(shù)前后凝血改變與臨床病理學之間的關(guān)系。材料與方法病人數(shù)據(jù)：在2014.6.1—2014.12.31于山東大學齊魯醫(yī)院乳腺外科住院就診的108名乳腺癌患者及20名良性乳腺腫瘤患者參與了研究。所有參與者均單純行手術(shù)治療,其中乳腺癌患者中,93名患者行單側(cè)乳腺癌改良根治術(shù),11名患者行單側(cè)乳腺癌根治術(shù),3名患者行雙側(cè)乳腺癌改良根治術(shù)。1例因病理類型較好,行單側(cè)乳房皮下腺體切除術(shù)。病人的臨床及病理特征見表1。方法：所有參與研究的患者均無肝腎疾病、血液病史,近2周內(nèi)無血栓及感染性疾病史。所有患者均無使用阿司匹林、華法林等影響凝血或止血藥物。所有患者在術(shù)前及術(shù)后第2天空腹狀態(tài)下靜脈采血。血液分析使用血細胞分析儀,所用試劑、質(zhì)控物等均為原裝配套試劑。采血使用的試管為EDTA抗凝管(采血量為5ml,內(nèi)含3.6mg EDTA-K2)。試劑為原裝配套試劑。PT、APTT使用凝同法測定。我們對患者的血漿凝血酶原時間(PT)、凝血酶原標準化比率(INR)、凝血酶原時間活動度(PTA)、凝血酶原時間比率(PTR)、活化部分凝血活酶時間(APTT)纖維蛋白原(Fib)、凝血酶時間(TT)、D-二聚體(D-dimer)進行統(tǒng)計和分析。所有乳腺癌患者均有病理學診斷。病理切片為石蠟切片,并經(jīng)過HE染色。腫瘤分級是根據(jù)修改后的布魯姆理查森評分系統(tǒng)。雌激素受體(ER)、孕激素受體(PR),和her-2狀態(tài)評估的是通過使用適當?shù)目贵w進行檢測。結(jié)果：1.從2014.6-2014.12,一共有108名患者參與了研究,平均年齡是50歲(年齡在27-76之間)(圖1),在這108名患者中,均單純經(jīng)過手術(shù)治療,手術(shù)方式包括單側(cè)乳腺癌改良根治術(shù)(93例)、單側(cè)乳腺癌根治術(shù)(11例)、雙側(cè)乳腺癌改良根治術(shù)(3例)、單純?nèi)橄偾谐g(shù)(1例)、三種。2.乳腺癌患者與良性乳腺腫瘤患者術(shù)前凝血的比較所有的良性乳腺腫瘤患者均無惡性腫瘤病史,通過比較兩者術(shù)前的凝血系列指標,我們發(fā)現(xiàn)兩者在APTT(P0.04)存在明顯差異,而其他指標沒有明顯差異。3.乳腺癌患者與良性乳腺腫瘤患者術(shù)后凝血的比較我們可以看出FIB(P0.001)、APTT (P0.001)、TT(P0.003)、PTA (P0.05)存在明顯差異,同時我們發(fā)現(xiàn)有些趨勢,乳腺癌患者術(shù)后PT(P=0.09)、INR(P=0.06)、PTR(P=0.07)增高,但是都沒有統(tǒng)計學意義。4.乳腺癌患者、良性乳腺腫瘤患者術(shù)前術(shù)后凝血變化的比較在乳腺癌患者中,術(shù)前術(shù)后所有的凝血系列指標的變化均有統(tǒng)計學意義。而在對照組中,只有(P=0.003)、FIB (P0.001)、TT (P=0.023)具有統(tǒng)計學意義.5.年齡(≥50),其術(shù)后凝血酶原活動度下降更明顯(-11.5 vs-5.7,P=0.01),而且術(shù)后D-二聚體升高更明顯(0.35 vs 0.14)。同時,年齡也影響了INR,年齡(≥50歲)的患者,其INR升高更明顯(0.06 vs 0.04,P=0.04)。絕經(jīng)期在一定程度上與年齡相關(guān),兩者存在共同點,都能使PTA下降(-11.7 vs-5.5,P=0.01)、INR升高(0.07 vs 0.03,P=0.01)更明顯。兩者也在一些項目上存在差異。絕經(jīng)能使PT延長更明顯(0.76 vs 0.36,P=0.01)、APTT下降不明顯(-1.5 vs-2.6,P=0.01)同時絕經(jīng)表現(xiàn)出一種趨勢,術(shù)后D-二聚體升高更明顯,但是P值大于0.05,因而也沒有統(tǒng)計學意義。第一胎生育年齡(≥25歲)與第一胎生育年齡(25歲),兩組在術(shù)后D-二聚體上存在差異。第一胎生育年齡(25歲)的患者其術(shù)后D-二聚體的水平升高(0.36 vs 0.15,P=0.05)更明顯。而初潮年齡、家族惡性腫瘤病史、超重對乳腺癌患者術(shù)前術(shù)后凝血變化無影響。腫瘤的大小對手術(shù)前后凝血指標的變化沒有影響,而淋巴結(jié)的狀態(tài),與一些指標相關(guān)。如淋巴結(jié)轉(zhuǎn)移的患者,其手術(shù)前后PTA下降(-10.9 vs-5.8,P=0.02)、TT下降(-1.8 vs-1.3,P=0.04)的更明顯。組織學越高,其術(shù)后PTA下降(-14.9 vs-7.5,P=0.02)的越明顯,D-二聚體升高(0.52 vs 0.2)的越明顯。雌激素受體的狀態(tài)對乳腺癌患者手術(shù)前后凝血指標的變化沒有影響,而孕激素受體陰性患者其術(shù)后纖維蛋白原升高(1.48vs 1.15,P=0.02)更明顯。P53基因和Her-2基因?qū)θ橄侔┗颊呤中g(shù)前后凝血指標改變沒有影響。而Ki67(≥20%)的患者其術(shù)后纖維蛋白原升高(1.06 vs 1.46,P=0.04)更明顯結(jié)論：像腫瘤的微環(huán)境和免疫反應(yīng)一樣,凝血系統(tǒng)被認為是一種影響腫瘤發(fā)展的的重要因素.相對于正常人或者良性腫瘤患者,乳腺癌患者體內(nèi)凝血系統(tǒng)已經(jīng)出現(xiàn)改變或者處于一種脆弱狀態(tài).通過實驗組與對照組比較,我們看到APTT確實存在差異,而APTT是內(nèi)源凝血系統(tǒng)較敏感和最為常用的篩選試驗.乳腺癌患者與良性乳腺腫瘤患者手術(shù)前后凝血指標均發(fā)生了不同程度的改變,并且乳腺癌患者術(shù)后凝血指標與良性乳腺腫瘤患者之間存在差異。這說明乳腺癌患者術(shù)后其凝血系統(tǒng)改變更多、更大。相比于良性乳腺腫瘤患者,乳腺癌患者術(shù)后可能存在更高的血栓風險。此外年齡(≥50歲)、絕經(jīng)、第一胎生育年齡(25歲)與乳腺癌患者手術(shù)前后凝血指標變化相關(guān),而初潮年齡(15歲)、超重、家族惡性腫瘤病史對乳腺癌患者手術(shù)前后凝血改變無關(guān)。在病理特征上,腫瘤的大小對手術(shù)前后凝血指標的變化沒有影響,而淋巴結(jié)的陽性則顯示了一些陽性結(jié)果。組織學分級越高,其術(shù)后凝血指標改變越大,特別是引起D-二聚體水平升高的更明顯,這說明高組織學分級的患者,其術(shù)后血栓風險增高。在免疫組化方面,雌激素與乳腺癌患者手術(shù)前后凝血指標變化無影響。而孕激素受體陰性的患者其纖維蛋白原水平升高,可能孕激素受體陽性是術(shù)后血栓的保護因素。P53基因和Her-2基因?qū)θ橄侔┗颊呤中g(shù)前后凝血指標的變化沒有影響,而Ki67≥20%的患者其術(shù)后纖維蛋白原水平升高的更明顯,說明Ki67≥20%的乳腺癌患者其術(shù)后血栓風險增加。總之,乳腺癌患者手術(shù)前后,所有的凝血項目都發(fā)生了有意義的改變,而且這種改變是與絕經(jīng)狀態(tài)、淋巴結(jié)狀態(tài)、組織學分級相關(guān)的。
[Abstract]:Background: through continuous research, people gradually recognize the role of the relationship between the tumor and the coagulation system in the progression of breast cancer. In fact, all parts of the blood clotting system, including platelets, prothrombin systems, and fibrinolytic systems, have affected the progress of many known breast cancer processes. The coagulation system has changed. In patients, the activation of the proto oncogene and the hypoxia in the local microenvironment can promote the overexpression of the tissue factor, activate the coagulation system, cause coagulation factor changes in the body and cause thrombus. Therefore, the patients with benign breast cancer may have the changes of coagulation before operation, and the surgical trauma is also possible. It can cause changes in the blood clotting system and the formation of thrombus. It is not clear how the blood clotting system changes after the operation of the breast cancer patients. The patients with breast cancer may have complications such as venous embolism and pulmonary embolism after operation. Once these complications occur, the patients' body and mind and economy can be caused by certain pressure and prolonged suffering. The purpose of this article is to explore the relationship between coagulation changes before and after operation of.2. breast cancer patients with.2. breast cancer and the relationship between coagulation changes and Clinicopathology before and after operation. Human data: 108 breast cancer patients and 20 benign breast cancer patients hospitalized at 2014.6.1 - 2014.12.31, Qilu Hospital, Shandong University, participated in the study. All the participants were treated with surgery alone. Among the patients with breast cancer, 93 patients underwent unilateral breast cancer modified radical mastectomy and 11 patients underwent unilateral breast cancer. Radical mastectomy, 3 patients underwent modified radical mastectomy for bilateral breast cancer,.1 cases with better pathological type, and unilateral breast subcutaneous gland resection. The clinical and pathological features of the patients were shown in table 1.. All the patients who participated in the study had no liver and kidney disease, blood history, no history of thrombus and infectious diseases within 2 weeks. All patients did not use aspirin. Lin, Hua Falin and other drugs affecting coagulation or hemostasis. All patients were collected in the venous blood under second sky abdominal conditions before and after operation. Blood analysis used blood cell analyzer, reagents used, quality control materials and so on. The test tube used for blood collection was EDTA anticoagulant tube (the amount of blood collection was 5ml, containing 3.6mg EDTA-K2). The reagent was the original kit. PT and APTT were measured by coagulant method. The plasma prothrombin time (PT), prothrombin standardization ratio (INR), prothrombin time activity (PTA), prothrombin time ratio (PTR), activated partial thromboplastin time (APTT) fibrinogen (Fib), thromboplastin time (TT), D- two polymer (D-dimer) were counted and analyzed. The patients with breast cancer have a pathological diagnosis. The pathological sections are paraffin sections and stained with HE. The tumor classification is based on the modified Blum Richardson scoring system. The estrogen receptor (ER), progesterone receptor (PR), and the HER-2 state are assessed by the use of appropriate antibodies. Results: 1. from 2014.6-2014.12, a total of 108. The patients were involved in the study, with an average age of 50 years (age 27-76) (Figure 1). In these 108 patients, all the patients were treated simply by surgical treatment, including unilateral breast cancer modified radical mastectomy (93 cases), unilateral radical mastectomy (11 cases), bilateral breast cancer modified radical mastectomy (3 cases), simple mammary gland resection (1 cases), three.2. breast cancer patients. Compared with preoperative coagulation, all patients with benign breast tumors had no history of malignant tumor. By comparing the preoperative coagulation series, we found that there were significant differences in APTT (P0.04), while other indicators did not significantly differ from.3. breast cancer patients and benign breast cancer patients. We can see that FIB (P0.001), APTT (P0.001), TT (P0.003), and PTA (P0.05) have obvious differences. At the same time, we found some trends in breast cancer patients, PT (P=0.09), INR (P=0.06), and increased, but no statistically significant breast cancer patients, patients with benign breast tumors were compared to breast cancer before and after operation. In the patients, all the changes of blood coagulation series before and after the operation were statistically significant, but in the control group, only (P=0.003), FIB (P0.001), TT (P=0.023) had statistical significance.5. age (> 50), and the decrease of prothrombin activity after operation was more obvious (-11.5 vs-5.7, P=0.01), and the increase of D- two polymer after operation was more obvious (0.35 vs 0.14). At the same time, age also affects INR, the age (50 years old) of the patients, the INR increase is more obvious (0.06 vs 0.04, P=0.04). Menopause is related to age to a certain extent, the two exist in common, can make PTA (-11.7 vs-5.5, P=0.01), INR increase (0.07 vs 0.03, P=0.01) more obvious. Both are also different in some items. Menopause can make PT The prolongation was more obvious (0.76 vs 0.36, P=0.01), and the decrease of APTT was not obvious (-1.5 vs-2.6, P=0.01) and menopause showed a trend, and the elevation of D- two polymer was more obvious after operation, but the value of P was greater than 0.05, so there was no statistical significance. The first birth age (25 years old) and the first birth age (25 years) and the two groups were different in the postoperative D- two polymer. The level of D- two polymer (0.36 vs 0.15, P=0.05) was more obvious after the first birth age (25 years old). The age of the menarche and the history of the family malignant tumor had no effect on the changes of blood coagulation before and after the operation. In patients with lymph node metastasis, PTA decreased (-10.9 vs-5.8, P=0.02) before and after operation, and TT decreased (-1.8 vs-1.3, P=0.04). The higher histology, the more obvious the postoperative PTA decreased (-14.9 vs-7.5, P=0.02), the more obvious the two polymer was raised (0.52) 0.2. The status of estrogen receptor in breast cancer patients' blood coagulation before and after operation The changes in the index were not affected, but the increase of fibrinogen (1.48vs 1.15, P=0.02) in the progesterone negative patients (P=0.02) was more obvious that the.P53 and Her-2 genes had no effect on the changes of blood coagulation indexes before and after the operation of breast cancer patients. And the postoperative increase of fibrinogen (1.06 vs 1.46, P=0.04) in patients with Ki67 (> 1.06) was more obvious: As the microenvironment of the tumor is the same as the immune response, the coagulation system is considered to be an important factor affecting the development of the tumor. Compared to the normal or benign tumor patients, the blood coagulation system in the breast cancer patients has changed or is in a fragile state. Compared with the control group, we see that the APTT does not exist. APTT is a more sensitive and most commonly used screening test for the internal blood coagulation system. The blood coagulation indexes of breast cancer patients and benign breast cancer patients vary in varying degrees, and there are differences between postoperative coagulation indexes and benign breast tumors in breast cancer patients. This shows the blood coagulation system of breast cancer patients after operation. Compared with benign breast cancer patients, breast cancer patients may have higher risk of thrombosis. Besides, age (50 years old), menopause, first birth age (25 years) are related to changes in blood coagulation indexes before and after operation of breast cancer patients, and the age of early menarche (15 years old), overweight, and family history of malignant tumor to breast cancer patients The changes in blood coagulation before and after the operation were not related. On pathological features, the size of the tumor did not affect the changes of blood coagulation indexes before and after the operation, while the positive lymph nodes showed some positive results. The higher the histological grade, the greater the changes in the postoperative coagulation index, especially the higher level of the D- two polymer, indicating the high organization score. There is no effect on the changes of blood coagulation indexes in the patients with breast cancer before and after operation, while the level of fibrinogen in the patients with progestin receptor negative is higher, and the positive of progestin receptor is the protective factor.P53 gene and the Her-2 gene for the operation of breast cancer patients. There was no effect on the changes in the index of the Precoagulation and blood coagulation, and the increased levels of fibrinogen in the patients with Ki67 > 20% were more obvious, indicating that the risk of postoperative thrombosis increased in the patients with Ki67 more than 20% of breast cancer. Lymph node status, histological grade related.

【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R737.9

【引證文獻】

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1 龐軼;黃源;李佳圓;李卉;陶萍;王瓊;李卉;黃蓉;李暢暢;;651例女性乳腺癌臨床流行病學特征及預(yù)后分析-10年回顧性研究[A];全國腫瘤流行病學和腫瘤病因?qū)W學術(shù)會議論文集[C];2011年

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本文編號：1839154