从厥阴、中气治疗神经母细胞瘤化疗不良反应的临床研究

发布时间：2018-05-14 21:22

本文选题：厥阴 + 中气　；参考：《南方医科大学》2016年硕士论文

【摘要】：研究背景神经母细胞瘤多原发于肾上腺,是小儿时期最普遍的实体肿瘤,其具有恶性程度高,临床症状复杂的特点,且易发生复发、转移,对儿童的生命健康构成严重的威胁。神经母细胞瘤的综合治疗主要包括外科切除及放化疗治疗,而化疗手段是中晚期神经母细胞瘤治疗的最重要的治疗方法之一。由于神经母细胞瘤患儿一般年龄小,脏器功能尚未完善,接受化疗后容易出现恶心呕吐、纳差、便秘、乏力、脱发等不良反应,这些不良反应阻碍了患儿顺利完成化疗的进程,或者直接拒绝化疗,严重影响综合治疗的疗效及患儿的预后。因此,儿童神经母细胞瘤治疗中对化疗不良反应的控制不容忽视。目前针对化疗药物的不良反应,西医药只能做到对症处理,现今临床上仍没有可以拮抗化疗不良反应的药物。从中医学的角度来看,化疗对肿瘤细胞和正常细胞缺乏精确的选择作用,这种不精确性相对正气而言则是一种邪气,有学者认为其属于毒邪,在治疗肿瘤的同时对脏腑和气血津液皆有严重的毒害作用。植根于中华优秀文化的祖国医学,其“整体观念、辨证论治”的特点在治疗肿瘤中发挥独特的作用,在治疗肿瘤中既能祛邪又可扶正。现代实验研究显示,中医药在临证时针对不同个体、不同时期进行辨证论治,能扶助正气,提高人体的抗病能力,大大缓解患者肿瘤患者化疗期间出现的症状,提高治疗疗效。神经母细胞瘤在中医学无相关记载,但据临床症状及相关检查,可归为“血证”、“虚劳”、“ve瘕”、“腹痛”、“积聚”、“鼓胀”等疾病的范畴。中医对神经母细胞瘤发病学的认识与其他肿瘤一致,首先强调人体正气对神经母细胞瘤发病的重要意义。现代医家认为该病的发生或因先天禀赋偏弱,母体遗毒,或因后天喂养失调,中气虚损,导致脏腑功能不足,正气不固,邪气因而内生,出现痰、湿、血、瘀等病理产物堆积而成癌毒,发展为此病。目前神经母细胞瘤尚无统一的中医辨证分型标准。近年来,相继有报道中医与化疗联合治疗可缓解神经母细胞瘤患儿化疗不良反应并减少医源性疾病的发生,提高了患儿的生存质量。所以在中晚期神经母细胞瘤化疗中配合中医药治疗,以防治化疗不良反应是一种临床上行之有效的方法。导师吕英教授立足“气一元论”学说归纳神经母细胞瘤病机为先天元阳禀赋不足,三阴冰伏,六气乖乱,绞结成形。导师认为生命本原的元气推动人之生命活动,并且疾病发生也是“本气自病”所致：厥阴和缓有序的升发,使元气升发至全身各处,推动了生命的气化活动,这是肝主疏泄功能的发挥,所以肝是元气萌芽之脏,是万物生命活力的体现,人身一气周流除了生发之力外,厥阴和缓有序的升发之力是人之生机另一关键；此外,中气为后天之本,不仅吸收精微物质至全身,营养脏腑、全身,又能充养元气,若中气虚弱,健运不力,元气不充,各种疾病由此而发；根气、中气、萌芽对应三阴三阳中的少阴、太阴、厥阴,故此三者又可以称为三阴本气,与元气密切联系。导师总结神经母细胞瘤患儿化疗不良反应主要表现在厥阴、中气两方面,临床上常分别用来复汤、理中汤为基础方加减对治,治疗上注重呵护神经母细胞瘤患儿受损之三阴本气,以期恢复患儿与生俱来的一气周流的圆运动,取得“但扶其正,听邪自去”良好的临床疗效。研究目的从厥阴、中气入手,分别以来复汤、理中汤为基础方,在化疗过程配合中药治疗神经母细胞瘤,探讨总结一套有效减轻化疗不良反应、改善患儿生活质量的中医药治疗方案。研究方法经病理组织学或骨髓检测确诊为神经母细胞瘤,参照INSS分期,选择临床分期为Ⅲ～-Ⅳ期的患儿,根据化疗中患儿出现的临床表现,纳入符合气虚证、脾气虚证诊断标准的病例。经严格标准筛选病例,共有25例神经母细胞瘤病例符合纳入标准,对25例病例进行3个治疗周期的回顾性研究,研究方法采用自身前后对照,分为治疗前(纯化疗)1个治疗周期、治疗后(化疗+中药)2个治疗周期。对化疗后出现精神疲劳乏力,气虚不足以息,气喘或气促,汗多,脉细弱或搏指等症状,证属厥阴萌芽之气升发不力,选用来复汤加减治疗；对化疗后出现食欲不振,饥不欲食或食量明显减少,体重减轻,肌肉松软,或恶心欲呕,大便质软烂或先干硬后软烂,舌淡,脉细弱或沉等症状,证属中气不足,运化不力,选用理中汤加减治疗。通过统计治疗前后化疗不良反应发生情况及其评分、临床症状缓解的疗效观察、血常规计数变化,比较分析治疗前后化疗不良反应的差异。采用SPSS 19.0统计软件进行统计的数据分析。计量资料先进行正态分布检验,符合正态性分布数据采用t检验,不符合正态性分布的数据采用非参数检验。计数资料采用χ2检验方法分析,以P0.05为差异有统计学意义。结果化疗不良反应发生情况及其评分方面,治疗前后对比,中药治疗后患儿恶心欲呕、食欲不振、体重减轻、大便不调、疲乏、汗多、气短的症状均较前减轻,与治疗前相比,差异均有统计学意义(P0.05)；其中患儿恶心欲呕、气短的症状,第2个疗程比第1疗程的效果较好,差异有统计学意义(P0.05)；食欲不振、大便不调的症状,第2疗程与第1疗程相比,差异无统计学意义(P0.05)；体重减轻、疲劳、汗多的症状,第1疗程症状明显未见减轻,差异无统计学意义(P0.05),而在第2疗程中缓解明显,差异有统计学意义(P0.05)。患儿疼痛、失眠、脱发症状治疗前后比较,差异均无统计学意义(P0.05)。临床症状缓解的疗效观察,中药治疗的第1疗程中部分改善12例(48%),无改善13例(52%)临床症状缓解总有效率(显著改善+部分改善)为48%。中药治疗的第2疗程中显著改善1例(4%),部分改善17例(68%),无改善7例(28%),临床症状缓解总有效率为72%。两疗程相比,差异有统计学意义(P0.05)。血常规计数比较,治疗后患儿化疗前后白细胞、血红蛋白、血小板计数的变化幅度均较治疗前下降,差异均有统计学意义(P0.01)；而中药第1疗程与中药第2疗程对比,差异无统计学意义(P0.05)。结论从厥阴、中气入手的中医药治疗方案配合化疗,在一定程度上有效缓解中晚期神经母细胞瘤患儿化疗不良反应,并随着中药治疗时间的延长而增加临床疗效,对化疗导致的骨髓抑制有一定的缓解作用,提高了患儿的生活质量；但对疼痛、失眠、脱发症状缓解未见明显效果。讨论本研究中药治疗后患儿恶心欲呕、食欲不振、体重减轻、大便不调、疲乏、汗多、气短的症状均较前减轻；其中恶心欲呕、气短、体重减轻、疲劳、汗多,在中药第2疗程治疗后明显改善,中药第2疗程的临床症状缓解总有效率比中药第1疗程高,说明中药治疗时间长短与临床疗效有密切关系。中药治疗后,虽然仍存在骨髓抑制,但患儿化疗前后外周血白细胞、血红蛋白、血小板计数的下降幅度均较治疗前降低,说明中药治疗对化疗的骨髓抑制有一定的缓解作用。综上所述,从厥阴、中气入手的中医药治疗方案配合化疗,在一定程度上缓解中晚期神经母细胞瘤患儿化疗不良反应,并随着中药治疗时间的延长而增加临床疗效。而患儿疼痛、失眠、脱发症状治疗前后比较未见明显改善,究其原因,由于患儿的三阴本气不足,需较长的治疗时间恢复本气,慢慢纠正体质,中药方能发挥作用,改善症状,再者患儿临床症状复杂多变,同一症状涉及的病因病机复杂,难以一一把握。患儿疼痛的症状,其根源为元阳不足,三阴冰伏,但考虑患儿化疗后三阴本气不足更是虚损,中气失运、厥阴升发不力,不宜直接采取“破冰回阳”来对治,只能通过调治中气、厥阴来恢复本气,故而症状缓解不明显：如失眠症状,总体属阳不入阴,是飘浮游离之阳“壮火食气”的亢奋状态,不是单纯通过引浮游之火归位就能解决,还需结合其他症状分析相火的来源。再如脱发,依《黄帝内经》“发为血之余”、“肾主骨,生髓,其华在发”之理,虽然治疗中顾护三阴本气,随着化疗疗程增加,三阴本气愈加虚损,而有形之血不能速生,故症状不能有效缓解,此亦是中医药难缓解化疗导致的骨髓抑制作用的原因。
[Abstract]:Background neuroblastoma is most commonly found in the adrenal gland. It is the most common entity tumor in childhood. It has high malignancy and complicated clinical symptoms, and is prone to recurrence and metastasis. It poses a serious threat to the life and health of children. The combined treatment of neuroblastoma mainly includes surgical resection and radiotherapy and chemotherapy. Treatment of neuroblastoma is one of the most important treatments for advanced neuroblastoma. Children with neuroblastoma are usually of small age and the organ function is not perfected. After chemotherapy, nausea and vomiting, nausea, constipation, fatigue and alopecia are easy to occur. These adverse reactions obstruct the children's successful completion of the process of chemotherapy, or Direct refusal of chemotherapy has seriously affected the curative effect of comprehensive treatment and the prognosis of children. Therefore, the control of adverse reactions to chemotherapy in the treatment of neuroblastoma in children can not be ignored. At present, western medicine can only deal with the adverse reactions of chemotherapeutic drugs, and there is still no drug that can antagonize the adverse reaction of chemotherapy. From the point of view of traditional Chinese medicine, chemotherapy is lacking in precise selection of tumor cells and normal cells. This inaccuracy is a kind of evil in relative positive gas. Some scholars believe that it belongs to the evil evil. At the same time, it has serious toxicity to the viscera and Qi and blood in the treatment of the tumor. The characteristics of "overall concept, syndrome differentiation and treatment" play a unique role in the treatment of tumors and can not only dispel evil spirits but also help to correct them in the treatment of tumors. Modern experimental research shows that traditional Chinese medicine can help the positive Qi, improve the body's resistance to disease, and greatly alleviate the chemotherapy of patients with tumor. There are no related records of neuroblastoma in traditional Chinese medicine, but according to clinical symptoms and related examinations, it can be classified as "blood syndrome", "virtual labor", "ve", "abdominal pain", "accumulation", "bulging" and other diseases. It emphasizes the important significance of the body positive gas to the disease of neuroblastoma. Modern doctors believe that the occurrence of the disease is caused by the congenital weakness of the natural endowment, the maternal body poison, the deficiency of the middle gas, the deficiency of the middle Qi, the inadequacy of the viscera, the evil spirit and the accumulation of the pathological products of phlegm, dampness, blood and blood stasis. At present, there is no unified TCM Syndrome Differentiation Standard for neuroblastoma. In recent years, it has been reported that combined treatment of Chinese medicine and chemotherapy can relieve the adverse reaction of neuroblastoma and reduce the occurrence of iatrogenic diseases and improve the quality of life of the children. To prevent and cure the adverse reaction of chemotherapy is a clinically effective method. Professor Lv Ying, based on the theory of "Qi monism", concludes that neuroblastoma is a congenital Yuanyang deficiency, three yin volts, six Qi disorderly, and stranded forming. The tutor thinks the vital qi of life pushes the life of human beings, and the disease occurs is " The Qi is caused by the disease: the Qi Yin and the slow and orderly rise and hair rise to all parts of the body to promote the whole body of the whole body and promote the gasification of life. This is the function of the main discharge of the liver, so the liver is the dirty of the sprout of the Qi and the embodiment of the vitality of all things. In addition, the central gas is the day of the day, not only to absorb the fine material to the whole body, nourishment Zang Fu organs, the whole body, but also can fill in the Qi, if the medium Qi is weak, the health is ineffective, the Qi is not filled, and the various diseases are caused by it, the root, middle Qi and bud are corresponding to the less Yin, the Yin and the Yin of the three yin, so the three can also be called the three Yin Qi, and yuan. The chemotherapy adverse reactions of the children with neuroblastoma were mainly manifested in the two aspects of syncope Yin and middle Qi, which were often used to recover the decoction, and the decoction of Lizhong was used as the basis for treatment. The treatment was focused on protecting the damaged three Yin Qi of the children with neuroblastoma. The purpose of this study is to achieve the good clinical effect of "but help its positive, listen to evil self". The purpose of this study is to discuss and summarize a set of effective treatment regimens for reducing the adverse reaction of chemotherapy and improving the quality of life of the children. The diagnosis of neuroblastoma was diagnosed by histopathology or bone marrow examination. According to INSS staging, children with stage III to IV were selected. According to the clinical manifestations of the children in chemotherapy, the cases were included in the diagnosis standard of qi deficiency syndrome and spleen qi deficiency syndrome. After strict standard screening, 25 cases of neuroblastoma were in conformity with the inclusion criteria. Retrospective study of 25 cases of 3 period of treatment, the study method was divided into 1 treatment cycles before and after treatment (pure chemotherapy), and 2 treatment cycles after treatment (chemotherapy plus traditional Chinese Medicine). After chemotherapy, there were symptoms of mental fatigue, asthenia, asthma or pony, sweating, weak pulse or stroke. The sprout gas is not strong enough to use the decoction of Lai Fu Tang to add and subtract the treatment. After the chemotherapy, there is no appetite, hunger or appetite, loss of weight, weight loss, muscle soft, nausea and vomiting, soft shit or dry hard rotten, weak tongue, weak pulse or sink, etc. The occurrence and score of adverse reaction of chemotherapy before and after treatment, the effect of clinical symptom remission, the change of blood routine count, and the difference of the adverse reaction of chemotherapy before and after treatment were compared and analyzed. The statistical data were analyzed with SPSS 19 statistical software. The advanced normal distribution of measurement data was tested in accordance with the normal distribution of t. Non parametric tests were used to test the data that did not conform to the normal distribution. The count data were analyzed by the chi 2 test method. The difference was statistically significant with P0.05. Results the incidence of adverse reactions to chemotherapy and its score, comparison before and after treatment, nausea and vomiting, loss of appetite, weight loss, defecation, fatigue and sweating were compared before and after treatment. The symptoms of shortness of breath were all less than before, and compared with before treatment, the difference was statistically significant (P0.05); the symptoms of nausea nausea and shortness of breath in children were better than the first course of treatment, the difference was statistically significant (P0.05); the loss of appetite, the disorder of bowel movement, and the second course compared with the first course of treatment, the difference was not statistically significant (P0.05 The symptoms of weight loss, fatigue and sweating, the symptoms of first courses were not significantly reduced, the difference was not statistically significant (P0.05), but in the second course of treatment, the difference was statistically significant (P0.05). The difference of pain, insomnia, and hair loss was not statistically significant before and after treatment (P0.05). In the first course of treatment, 12 cases (48%) were improved, no improvement in 13 cases (52%) of clinical symptom relieving total efficiency (significant improvement + partial improvement) was significantly improved in 1 cases (4%) in the second course of 48%. Chinese medicine treatment, 17 (68%) improved in 17 cases (68%), 7 (28%) was not improved, and the total effective rate of clinical symptomatic relief was statistically significant (P0 .05) compared with the blood routine count, the changes of white blood cells, hemoglobin and platelet count were all decreased before and after the treatment, and the difference was statistically significant (P0.01), while the difference between the first course of Chinese medicine and the second course of Chinese medicine was not statistically significant (P0.05). Chemotherapy, to a certain extent, effectively alleviates the adverse reaction of children with middle and advanced neuroblastoma, and increases the clinical efficacy with the prolongation of Chinese medicine treatment time. It has a certain relieving effect on bone marrow suppression induced by chemotherapy and improves the quality of life of the children, but there is no obvious effect on pain, insomnia and relieving symptoms of alopecia. In this study, the symptoms of nausea and vomiting, loss of appetite, weight loss, defecation, fatigue, sweating, and shortness of breath were all alleviated, among them nausea and vomiting, shortness of breath, weight loss, fatigue and sweating, after second courses of Chinese medicine treatment, the total effective rate of the second course of Chinese medicine was higher than the first course of Chinese medicine, There is a close relationship between the duration of Chinese medicine treatment and the clinical effect. After the treatment of Chinese medicine, there is still bone marrow suppression, but the decrease of leukocyte, hemoglobin and platelet count of peripheral blood before and after chemotherapy in children is lower than that before treatment, indicating that the treatment of Chinese Medicine has certain relieving effect on the suppression of bone marrow in chemotherapy. The Chinese traditional Chinese medicine treatment scheme combined with chemotherapy to some extent alleviated the adverse reaction of chemotherapy in children with middle and advanced neuroblastoma, and increased the clinical efficacy with the prolongation of the treatment time of Chinese medicine. Foot, need longer treatment time to restore the Qi, slowly correct the physique, Chinese medicine can play a role, improve the symptoms, and the clinical symptoms of children are complex and changeable, the same symptom involved in the etiology and pathogenesis of complex, difficult to grasp one by one. The symptoms of children's pain, the root of Yuanyang is not enough, three yin ice volts, but consider the children after chemotherapy three yin deficiency gas is more than more. It is the deficiency, the gas loss, the Qi Yin rise is not strong, it is not appropriate to directly take "ice breaking back to Yang" to treat, only by regulating the middle Qi, the Qi Yin to restore the gas, so the symptoms are not obvious relief: if the symptoms of insomnia, the overall Yang does not enter the Yin, is floating free Yang "strong fire food and gas" exuberance state, not simply through the exuberance of the fire return to the position Can be solved, still need to combine other symptoms to analyze the source of phase fire. Again like hair loss, according to "Yellow Emperor's Internal Classic", "hair for the blood", "kidney main bone, the pulp, its Chinese in hair", although the treatment of three yin to protect the Qi, as the chemotherapy treatment increases, three yin this gas more deficiency, and the tangible blood can not speed, so the symptoms can not effectively ease, this is also the symptoms can not effectively ease, this is also the symptoms can not effectively mitigate, therefore, the symptoms can not be effectively relieved. It is the reason why Chinese medicine is difficult to alleviate the myelosuppression induced by chemotherapy.

【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R273

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