腦膜癌病的預(yù)后因素分析及T細(xì)胞亞群的免疫狀態(tài)評(píng)估
發(fā)布時(shí)間：2019-05-19 07:48
【摘要】：目的:腦膜癌病(Meningeal carcinomatosis,MC)是惡性腫瘤細(xì)胞在腦脊液或腦膜多處種植的一種疾病。隨著診療技術(shù)的提高,腫瘤患者的生存期延長,腦膜癌病的發(fā)病率越來越高。治療腦膜癌病的主要目的是改善患者神經(jīng)系統(tǒng)癥狀、延長患者生存期。本研究旨在總結(jié)腦膜癌病患者的臨床特點(diǎn),評(píng)估其預(yù)后因素及免疫功能狀態(tài)。方法:回顧性分析2016年1月至2017年1月就診于河北醫(yī)科大學(xué)第二醫(yī)院的35例腦膜癌病患者的臨床資料。分析其臨床特點(diǎn);分析年齡、KPS(Karnofsky Performance Status)評(píng)分、原發(fā)癌癥、腦脊液蛋白含量、是否合并腦積水、頭顱增強(qiáng)核磁表現(xiàn)、是否進(jìn)行鞘內(nèi)聯(lián)合靶向治療、甲氨蝶呤劑量對(duì)患者預(yù)后的影響。測定患者外周血及腦脊液CD3+、CD3+CD4+、CD3+CD8+T細(xì)胞比例及CD3+CD4+/CD3+CD8+比值,并進(jìn)行比較。結(jié)果:1腦膜癌病多見于中老年患者,多呈亞急性起病,河北省內(nèi)地區(qū)分布以石家莊為主,原發(fā)癌以肺癌最常見,共20例,其次依次為胃癌7例,未明確腫瘤4例,乳腺癌、卵巢癌、前列腺癌、淋巴瘤各1例。臨床表現(xiàn)多樣,以高顱壓癥狀最常見,共28例,顱神經(jīng)受損的癥狀21例,表現(xiàn)為視力下降、視物成雙、聽力下降;脊髓或脊神經(jīng)受損的癥狀12例,表現(xiàn)為頸背部疼痛、肢體無力、尿潴留;共濟(jì)失調(diào)1例。35例行腦脊液細(xì)胞學(xué)檢查,首次發(fā)現(xiàn)腫瘤細(xì)胞者30例(85.7%)。19例行頭顱增強(qiáng)磁共振(Magnetic resonance imaging,MRI)檢查,13例表現(xiàn)為軟腦膜異常強(qiáng)化,其中6例同時(shí)存在腦實(shí)質(zhì)強(qiáng)化結(jié)節(jié)。18例進(jìn)行基因檢測,6例表皮生長因子受體(epidermal growth factor receptor,EGFR)21突變;6例EGFR19突變;3例T790M突變。2 23例患者接受了標(biāo)準(zhǔn)的鞘內(nèi)化療方案,標(biāo)準(zhǔn)鞘內(nèi)化療甲氨蝶呤15mg組和10mg組,癥狀的緩解率分別87.50%、33.33%,差異有統(tǒng)計(jì)學(xué)意義(P=0.027)。3截止至2017年1月1日,隨訪35例患者,17例仍存活。中位生存時(shí)間7.54個(gè)月。Kaplan-Meier單因素分析顯示原發(fā)癌種(P0.001)、是否合并腦積水(P=0.014)、KPS評(píng)分(P=0.001)及是否鞘內(nèi)聯(lián)合靶向治療(P=0.001)與患者的預(yù)后相關(guān)。多因素分析顯示KPS評(píng)分是影響腦膜癌病患者預(yù)后的獨(dú)立因素。4對(duì)16例腦膜癌病患者外周血及腦脊液T細(xì)胞亞群進(jìn)行分析,外周血CD8+T細(xì)胞比例大于正常值(P0.05),CD3+、CD4+T細(xì)胞及CD4+/CD8+比值與正常值比較無差異(P0.05)。而腦脊液CD3+、CD4+、CD8+T細(xì)胞比例高于正常值(P0.05),CD4+/CD8+比值低于正常值(P0.05),腦膜癌病患者外周血與腦脊液比較,腦脊液CD3+、CD4+、CD8+T細(xì)胞比例高于外周血(P0.05),CD4+/CD8+比值無差異(P0.05)。結(jié)論:1腦膜癌病多見于中老年人,常呈亞急性起病,河北省內(nèi)患者主要集中于石家莊地區(qū),原發(fā)癌以肺癌最常見。臨床表現(xiàn)變化多端、無特異性。腦脊液細(xì)胞學(xué)是診斷此病的金標(biāo)準(zhǔn),頭顱MRI增強(qiáng)掃描有助于診斷,基因突變檢測可指導(dǎo)用藥。2鞘內(nèi)化療甲氨蝶呤15mg可改善患者的癥狀,臨床醫(yī)師可根據(jù)患者病情采用此劑量進(jìn)行鞘內(nèi)化療。3原發(fā)癌種、是否合并腦積水、KPS評(píng)分及是否鞘內(nèi)聯(lián)合靶向治療與患者的預(yù)后相關(guān)。KPS評(píng)分是影響腦膜癌病患者預(yù)后的獨(dú)立因素。4 T細(xì)胞亞群檢測可成為判讀腫瘤患者細(xì)胞免疫狀態(tài)的一種手段,檢測腦膜癌患者腦脊液T細(xì)胞亞群數(shù)量可對(duì)其免疫狀態(tài)評(píng)估有一定的臨床意義。
[Abstract]:Objective: Meningeal carcinosis (MC) is a kind of disease in the cerebrospinal fluid or meninges of malignant tumor cells. With the improvement of the diagnosis and treatment technology, the survival time of the tumor patients is prolonged, and the incidence of meningeal cancer is higher and higher. The main purpose of the treatment of meningeal carcinomatosis is to improve the symptoms of the nervous system of the patient and prolong the survival time of the patients. The purpose of this study is to summarize the clinical features of meningocarcinoma and to assess the prognostic factors and immune function. Methods: The clinical data of 35 cases of meningocarcinoma in the second hospital from January 2016 to January 2017 were analyzed retrospectively. The clinical characteristics of the patients were analyzed. The age, the KPS (Karnofsky Performance Status) score, primary cancer, cerebrospinal fluid protein content, whether the hydrocephalus was combined, the magnetic performance of the head was enhanced, and the effect of the combination of the target therapy and the dose of methotrexate on the prognosis of the patients was investigated. The ratio of CD3 +, CD3 + CD4 +, CD3 + CD8 + T cells and the ratio of CD3 + CD4 +/ CD3 + CD8 + were determined and compared. Results:1. Meningeal carcinomatosis was found in middle-aged and old-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged patients. The distribution of primary cancer in Hebei province was mainly in Shijiazhuang. The primary cancer was the most common in lung cancer. 1 case of lymphoma. The clinical manifestations were diverse, with the most common symptoms of high-cranial pressure,28 cases, and 21 cases of cranial nerve damage, which showed that the visual acuity decreased, the visual acuity was double, the hearing decreased, and the symptoms of the spinal cord or the spinal cord were 12 cases, which showed the pain of the back of the neck, the weakness of the limbs and the retention of the urine; There were 30 cases of ataxia (85.7%) for the first time in 35 cases of ataxia.19 cases of brain-enhanced magnetic resonance (MRI) were examined, and 13 cases were abnormal enhancement of the meninges. In 6 of them, there were brain parenchyma strengthening nodules.18 cases were detected by gene,6 cases of epidermal growth factor receptor (EGFR)21 mutation,6 cases of EGFR19 mutation,3 cases of T790M mutation,23 of 23 patients received the standard intraoral chemotherapy, and 15 mg and 10 mg of the standard intraoral chemotherapy. The remission rate of the symptoms was 87.50%, 33.33%, and the difference was statistically significant (P = 0.027). The median survival time was 7.54 months. The Kaplan-Meier single-factor analysis showed that the primary cancer species (P0.001), the combined hydrocephalus (P = 0.014), the KPS score (P = 0.001), and the combined targeting treatment (P = 0.001) were associated with the patient's prognosis. Multi-factor analysis showed that the KPS score was an independent factor that affected the prognosis of the patients with meningeal cancer.4. The T-cell subsets in peripheral blood and cerebrospinal fluid of 16 patients with meningeal cancer were analyzed, and the ratio of CD8 + T cells in peripheral blood was higher than normal (P0.05), and CD3 +, There was no difference between the ratio of CD4 + T cells and CD4 +/ CD8 + to normal values (P0.05). The ratio of CD3 +, CD4 +, CD8 + T cells in the cerebrospinal fluid was higher than that of normal (P0.05). The ratio of CD4 +/ CD8 + was lower than normal (P0.05). The ratio of CD3 +, CD4 +, CD8 + T cells in the cerebrospinal fluid was higher than that of the peripheral blood (P0.05). The ratio of CD4 +/ CD8 + was not different (P0.05). Conclusion: Meningeal carcinomatosis is often seen in the middle-aged and the elderly, often subacute onset, and the patients in Hebei province are mainly concentrated in the Shijiazhuang area, and the primary cancer is the most common in the lung cancer. The clinical manifestations are variable and non-specific. Cerebrospinal fluid cytology is a gold standard for the diagnosis of the disease. The MRI-enhanced scan of the skull is helpful to the diagnosis and gene mutation detection. The 15 mg of methotrexate can improve the symptoms of the patient. The clinical physician can use this dose for intraoral chemotherapy according to the condition of the patient. Whether the combined hydrocephalus, the KPS score, and the combined targeting therapy in the patients were associated with the patient's prognosis. KPS score is an independent factor that affects the prognosis of patients with meningeal cancer.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R739.45
本文編號(hào)：2480531
[Abstract]:Objective: Meningeal carcinosis (MC) is a kind of disease in the cerebrospinal fluid or meninges of malignant tumor cells. With the improvement of the diagnosis and treatment technology, the survival time of the tumor patients is prolonged, and the incidence of meningeal cancer is higher and higher. The main purpose of the treatment of meningeal carcinomatosis is to improve the symptoms of the nervous system of the patient and prolong the survival time of the patients. The purpose of this study is to summarize the clinical features of meningocarcinoma and to assess the prognostic factors and immune function. Methods: The clinical data of 35 cases of meningocarcinoma in the second hospital from January 2016 to January 2017 were analyzed retrospectively. The clinical characteristics of the patients were analyzed. The age, the KPS (Karnofsky Performance Status) score, primary cancer, cerebrospinal fluid protein content, whether the hydrocephalus was combined, the magnetic performance of the head was enhanced, and the effect of the combination of the target therapy and the dose of methotrexate on the prognosis of the patients was investigated. The ratio of CD3 +, CD3 + CD4 +, CD3 + CD8 + T cells and the ratio of CD3 + CD4 +/ CD3 + CD8 + were determined and compared. Results:1. Meningeal carcinomatosis was found in middle-aged and old-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged patients. The distribution of primary cancer in Hebei province was mainly in Shijiazhuang. The primary cancer was the most common in lung cancer. 1 case of lymphoma. The clinical manifestations were diverse, with the most common symptoms of high-cranial pressure,28 cases, and 21 cases of cranial nerve damage, which showed that the visual acuity decreased, the visual acuity was double, the hearing decreased, and the symptoms of the spinal cord or the spinal cord were 12 cases, which showed the pain of the back of the neck, the weakness of the limbs and the retention of the urine; There were 30 cases of ataxia (85.7%) for the first time in 35 cases of ataxia.19 cases of brain-enhanced magnetic resonance (MRI) were examined, and 13 cases were abnormal enhancement of the meninges. In 6 of them, there were brain parenchyma strengthening nodules.18 cases were detected by gene,6 cases of epidermal growth factor receptor (EGFR)21 mutation,6 cases of EGFR19 mutation,3 cases of T790M mutation,23 of 23 patients received the standard intraoral chemotherapy, and 15 mg and 10 mg of the standard intraoral chemotherapy. The remission rate of the symptoms was 87.50%, 33.33%, and the difference was statistically significant (P = 0.027). The median survival time was 7.54 months. The Kaplan-Meier single-factor analysis showed that the primary cancer species (P0.001), the combined hydrocephalus (P = 0.014), the KPS score (P = 0.001), and the combined targeting treatment (P = 0.001) were associated with the patient's prognosis. Multi-factor analysis showed that the KPS score was an independent factor that affected the prognosis of the patients with meningeal cancer.4. The T-cell subsets in peripheral blood and cerebrospinal fluid of 16 patients with meningeal cancer were analyzed, and the ratio of CD8 + T cells in peripheral blood was higher than normal (P0.05), and CD3 +, There was no difference between the ratio of CD4 + T cells and CD4 +/ CD8 + to normal values (P0.05). The ratio of CD3 +, CD4 +, CD8 + T cells in the cerebrospinal fluid was higher than that of normal (P0.05). The ratio of CD4 +/ CD8 + was lower than normal (P0.05). The ratio of CD3 +, CD4 +, CD8 + T cells in the cerebrospinal fluid was higher than that of the peripheral blood (P0.05). The ratio of CD4 +/ CD8 + was not different (P0.05). Conclusion: Meningeal carcinomatosis is often seen in the middle-aged and the elderly, often subacute onset, and the patients in Hebei province are mainly concentrated in the Shijiazhuang area, and the primary cancer is the most common in the lung cancer. The clinical manifestations are variable and non-specific. Cerebrospinal fluid cytology is a gold standard for the diagnosis of the disease. The MRI-enhanced scan of the skull is helpful to the diagnosis and gene mutation detection. The 15 mg of methotrexate can improve the symptoms of the patient. The clinical physician can use this dose for intraoral chemotherapy according to the condition of the patient. Whether the combined hydrocephalus, the KPS score, and the combined targeting therapy in the patients were associated with the patient's prognosis. KPS score is an independent factor that affects the prognosis of patients with meningeal cancer.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R739.45
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