郁仁存老师学术思想、经验总结及健脾补肾法在肿瘤治疗中的应用
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摘要
郁仁存教授是我国著名的中西医结合肿瘤学专家,对恶性肿瘤的中医及中西医结合治疗有其独到的学术思想和治疗经验。通过参加全国第四批名老中医经验继承,师从郁仁存教授言传身教3年,总结导师主要学术思想、源流及形成过程,继承导师在肺癌、胃癌、乳腺癌、大肠癌、肝癌等常见肿瘤的临床经验以及独特的诊疗、用药思路,积累大量临床医案获取了丰富的第一手资料。
我将跟师期间的病案进行整理与总结,以导师临床用药为线索,将原始处方从多个角度进行分析对比、综合归纳,以导师健脾补肾学说理论精髓为依据,总结导师应用健脾补肾学说的临证经验、用药规律(包括常用药物功效、药性、药对),发掘导师中西医结合治疗肿瘤的学术思想、理论精髓以及对临床的指导意义。并应用健脾补肾法治疗化疗后白细胞减少症32例,在症状改善、白细胞的提升,免疫功能的提高方面与对照组有明显差异,印证了郁老健脾补肾扶正理论对临床的指导意义。
在肿瘤的病因方面,郁老提出了肿瘤发病的内虚学说、失衡学说,并以平衡理论、健脾补肾法则指导肿瘤防治。郁老认为“内虚”是肿瘤发生发展的关键因素,在癌症治疗中,脏腑功能、气血功能、病邪与正气之间的平衡是病情稳定的前提。肿瘤治疗的根本原则就是平衡阴阳、扶正祛邪,使机体达到新的平衡状态。“内虚学说”指导下,健脾补肾法是最重要的扶正法则。脾肾双补,资化源,养气血,益先天,脾肾功能正常,则脏腑气血阴阳调和平衡,清浊分流,积聚消弭。
郁老是国内最早提出“益气活血法”治疗肿瘤的中西医结合专家,这一观点的确立、深入研究对全国中医治疗肿瘤的学术发展起到积极的推动作用。郁老认为气虚血瘀证在肿瘤患者中普遍存在。益气活血法治疗肿瘤最关键的问题是治疗时机、药物、用量比例的选择。凡有气虚血瘀证及放化疗期间预防治疗均可应用益气活血法；原则上是选择经现代医学研究证明有提高细胞免疫功能及增强脏腑功能的益气药为君药,活血药也选择已证明对肿瘤细胞有抑制作用的、对免疫系统功能无明显抑制的活血化瘀药。益气药的用量应大于活血药(7：3--6：4),这样才符合“气行则血行”的益气活血法的根本宗旨。如果没有有效抗肿瘤的治疗(化疗或生物靶向治疗)时,则要加上已证实有抗肿瘤作用的抗癌中草药。
在治疗上,郁老提出了中西医结合治疗肿瘤途径和方法。四原则：辨证与辨病相结合,扶正与祛邪相结合,整体与局部相结合,近期治疗与长期调摄相结合。三结合：中医药与手术相结合,与化疗相结合,与放疗相结合。
辨证与辨病治疗相结合：郁老往往将中医辨证与肿瘤自身特有的发生发展规律相结合,除了弄清楚患者目前是属于中医辨证的何种类型,了解体内气血、阴阳、脏腑虚实、经络的情况,还要清楚所患的疾病种类、病理类型、分期、侵及部位及治疗阶段等辨病的内容,根据不同疾病不同阶段的特征进行施治。在遣药处方时,注重药物的双重功能,应用中药既符合中医辨证论治的理论,又结合药物药理作用,选用具有提高免疫功能、抑瘤作用的中药。
扶正与祛邪相结合：如病属早期,正气尚未大衰,治则应重在祛邪,尽可能地利用中西医各种手段打击和消灭肿瘤,同时注意保护正气；若患者正气受损,则在祛邪同时兼以扶正。若病已属晚期,正气虚弱,已不任攻伐,特别是又无有效药物,则应以扶正为主,少佐以祛邪抗癌。手术后及放化疗后的病人以扶正调理为主,但具有高危因素的肿瘤病人易出现复发转移,宜攻补兼施。
整体与局部相结合：早期以局部治疗为主,晚期以整体治疗为主,并以局部为辅。在局部肿瘤有条件有可能清除或减灭而机体一般又能胜任者,就要设法做好局部治疗；在局部病变已无法清除或机体宿主已无法胜任的情况下,则无法做局部治疗而着重在全身整体治疗。遵循“急则治其标”的原则,如果局部病况紧急或产生严重的后果或危急时,则要紧急处理作局部治疗,同时要分清主次。
近期治疗与长期调摄相结合：近期治疗以祛邪为主要目的,西医治疗手段在取得近期疗效方面有绝对的优势,中医药治疗可以起到很好的辅助作用。运用西医方法对肿瘤病灶进行彻底的治疗以后,应用中医药方法,对机体的阴阳平衡进行及时的调整,是阻止癌症复发、转移的有效途径,防治并重,长期服药巩固疗效。
中医药与手术相结合时,手术前以中药扶正为主,益气养血,健脾补肾,增强体质,改善患者营养状况,有利于手术的进行；术后则配合中药促进机体机能的尽快康复。与放疗相结合时,针对放射线热毒之邪耗气伤阴,损伤脾胃功能,同时阴液亏耗、血行淤滞,导致气虚血瘀证。治以益气养阴,生津润燥,调理脾胃,清热解毒,活血化瘀等法则来治疗,并根据不同部位和证候辨证施治。与化疗相结合时,郁老认为以健脾补肾方药效果最好,健脾养后天,补肾益先天,对骨髓造血功能、免疫功能有很大提高,并总结出分别针对红细胞下降、白细胞下降、血小板下降的经验方及有效中草药。
我将导师临床治疗肿瘤的668张原始处方从多个角度进行分析对比、综合归纳,发掘导师“随证用药”的规律如下：(1)各种肿瘤病人的治疗均含有健脾补肾处方用药,药味、药量依据病情、治疗阶段有所不同,但健脾补肾扶正法则贯穿始终。(2)以平衡学说为指导,根据病人病情分阶段治疗,不同阶段扶正、抗癌比重均有侧重。(3)遣方用药中涉及的179味药物,根据出现频次和频率分布归纳总结了19味最为常用药物,将它们重新组合成方,充分体现了导师扶正祛邪并举、注重健脾补肾的学术思想的核心内涵。(4)常用19味中药按药性理论进行分析,性温性平味甘的药物所占比例较大,说明温补、平补是导师扶正用药的核心理念,与其提倡肿瘤治疗的“平衡理论”相符合。另外苦寒药次之,说明清热解毒是其临床祛邪的常用治法。两者相合,体现了攻补兼施的原则。(5)临床组方中扶正补虚药物为主,清热解毒药、活血化瘀药、理气药为辅,同时采用疏肝理气、软坚散结、化痰除湿治法等从多方面多层次治疗,说明导师在辨证论治基础上遣方用药,主次分明,组合有序。(6)总结导师临床常用药对,实为用药精华之所在。(7)依据中医理论选方用药,结合现代药理研究进展,重视药物的双重功用,一药多用,体现了中西医结合理论防治肿瘤的优势。
郁老从事中西医结合肿瘤临床研究五十余年,在实践中逐步形成了独特的中西医结合治疗肿瘤的学术思想和宝贵经验,是我国中西医结合肿瘤学科的奠基人和带头人之一。以其学识渊博、中西汇通、经验丰富、疗效显著而享誉海内外。
目的：
1观察郁仁存教授健脾补肾法治疗化疗后白细胞减少症的临床疗效。
2观察其对临床症状、生活质量以及T淋巴细胞亚群的改善,探讨中医健脾补肾法治疗白细胞减少症的优势,为进一步研究健脾补肾法在肿瘤化疗中的应用提供前期的依据。
方法：
本研究采用随机对照、前瞻性试验方法。将符合入组的病人按1：1的比例随机分为治疗组和对照组,治疗组采用郁仁存教授健脾补肾基础方加减,对照组应用利血生,疗程2周,以白细胞计数、脾虚症状积分、生活质量评分、T淋巴细胞亚群为观察指标,评价健脾补肾法治疗白细胞减少症的确切疗效以及脾虚症状、生活质量的改善。
结果：
1白细胞减少改善率：治疗组白细胞减少症有效率为91%,对照组有效率为70%,经统计学分析,两组有显著差异(P<0.05)。治疗组白细胞升高的幅度也高于对照组,有显著差异(P<0.05)。
2脾虚证症状积分：两组病人症状总积分治疗后较治疗前均有下降,统计学分析有显著差异(P<0.05)；两组疗后总积分及治疗前后积分差值比较有显著性差异((P<0.05)。且治疗组在食欲不振、神疲乏力、腹胀典型症状的改善方面较对照组为优。
3生活质量评分：治疗组平均KPS评分较治疗前有提高,有统计学差异；对照组治疗前后KPS评分变化无统计学差异。两组的KPS改善率分别为84.4%、53.3%,两组比较有显著差异。
4外周血T淋巴细胞亚群：治疗组CD3、CD4、CD4/CD8三者经治疗后较治疗前有提高,但无显著差异。对照组三者疗后较疗前无明显改善。
5毒副反应：两组治疗后,均未见心、肝、肾功能损害。
结论：
1应用健脾补肾法治疗可以有效改善化疗后白细胞减少症,安全无毒副反应。
2应用健脾补肾法能改善化疗病人脾虚证的中医证候,提高生活质量。
Professor Yu Rencun, a famous specialist in Oncology with combination of Traditional Chinese Medicine (TCM) and Western Medicine in China, has possessed unique academic ideology and experiences in the treatment of TCM and combination medicine for malignant tumors. I have learned much knowledge from Professor Yu by participating in the fourth experience inheritance activity. During the three years, I summarized his main academic theory, origin and development, inherited his clinical experience and unique treatment for lung cancer, gastric cancer, breast cancer, colon cancer, liver cancer and so on, accumulated a large amount of clinical cases and acquired plenty of firsthand information.
I summarized all the cases, with the basis of clinical medicine, analyzed, contrasted and concluded the original prescriptions. Based on the theory of replenishing the spleen and kidney systems form my teacher, I summarized his clinical experiences, medicine regularity, which including the efficacy, nature and pairs of the common herbs, seek his academic thinking, theoretical essence and clinical significance. Besides,32 cases of Leucocytopenia after chemotherapy were treated by tonifying spleen and replenishing kidney method, which has shown significant difference in terms of symptoms alleviation, leukocyte increase and immunologic function improvement, proving the guiding significance of Professor Yu's theory in clinic.
In terms of the etiology of tumors, Professor Yu raised the theory of inner deficiency and imbalance. He treated and prevented tumors based on the theory of balance and the method of tonifying spleen and replenishing kidney. Inner deficiency was considered to be the key reason for the ongoing and development of tumors. For treatment, the functions of Zang Fu organs, Qi and blood, as well as the balance between pathogens and vital energy were the premises with stabilization of the disease. The cardinal principle for treatment was balancing Yin and Yang, replenishing vital energy and expelling pathogens, in order to achieve new balance. Based on the theory of inner deficiency, the method of tonifying spleen and replenishing kidney was the most important principle. By strengthening the spleen and kidney, the source was plenty and Qi and blood was replenished to balance the Qi, blood, Yin and Yang, and eliminate the mass.
Professor Yu was the first expert, in the field of combined TCM and Western Medicine, who put forward the replenishing Qi and activating blood circulation methods to treat tumors, and the view had activated the development of theories for the treatment of tumors in TCM. Considering that the syndrome of Qi deficiency and blood stasis was existed among the patients with tumors, the key problem for the method of replenishing Qi and activating blood circulation was the choice of therapeutic opportunity, drugs and dosage. The method could be adopted when syndrome of Qi deficiency and blood stasis, or for the prevention and treatment during radiotherapy or chemotherapy. The herbs, with the function of replenishing Qi, proved to be develop the immunologic function and the visceral function in modern medical research, were utilized as Jun medicine on principle, while those, with the function of activating blood circulation, confirmed to restrain the tumor cells but have little suppression for immune system, were chosen as well. The dosage of herbs for replenishing Qi should more than that for activating blood circulation (7:3-6:4), to satisfy the cardinal purpose of replenishing Qi and activating blood circulation method. When effective treatment for tumors, such as chemotherapy and biologic target therapy, the herbs with the function of expel tumors should be prescribed.
For the treatment in integration of TCM and Western Medicine, Professor Yu came up with four principles and three combinations. Four principles meant the combinations of syndrome differentiation and disease differentiation, vital energy strengthening and pathogens eliminating, systemic and local treatment as well as short-term therapy and long-term healthcare, while three combinations referred to Chinese herbs with operation, chemotherapy and radiotherapy.
The combination of syndrome differentiation and disease differentiation; Professor Yu always combined syndrome differentiation with the own rule of the tumors. Apart from making sure the syndrome the patient was suffering from to know the Qi, blood, Yin, Yang, the condition of Zang Fu organs and collaterals, the classification, pathological types, stage, location and phase should also be determined. Treatment was performed according to the characteristics in different stage of various diseases. When made prescriptions, attached importance on the double functions of Chinese herbs and chose the ones, which were able to improve the immune system and suppress the tumor, according to the theories of TCM and their pharmacological actions.
The combination of vital energy strengthening and pathogens eliminating; in the early stage, when vital energy was not exhausted, the treatment of eliminating pathogens was focused on. All kinds of methods of TCM or Western medicine should be adopted to eliminate tumors and should pay attention to vital energy as well. If vital energy was decreasing, the replenishing and eliminating methods should be utilized. For the patients in the advanced stage, when vital energy was too weak to receive medicine of expelling pathogens, especially for those without effective drugs, the method of replenishing vital energy was in lead, with a small amount of herbs for expelling tumors. The method of replenishing vital energy was mainly relied on for the patients after operation, radiotherapy or chemotherapy, while combined approach of replenishment and expulsion should be given for those with high risk factors, easy to have recurrence or metastasis.
The combination of systemic and local treatment; in the early stage, local treatment was focused on while in the advanced stage, systemic treatment was predominant. Local treatment should be performed when the localized tumor could be eliminated and the patient was suitable, while systemic treatment was utilized when the localized tumor was unable to be eliminated or the patient was not suitable. If the localized condition was serious or urgent, local treatment should be performed first.
The combination of short-term therapy and long-term healthcare; Methods in Western Medicine had absolute advantage on short-term efficacy while TCM could play a supplementary role. After the complete treatment for tumor by Western Medicine, the application of TCM, which was used to adjust the balance of Yin and Yang, was an effective way to prevent recurrence or metastasis.
When TCM was combined with operation, Chinese herbs of replenishing function were mainly prescribed before the operation to strengthen Qi, nourish blood, tonify spleen and replenish kidney to strengthen the constitution, improve the patient's nutritional status and make the operation perform smoothly. While postoperative treatment principles with Chinese herbs focused on sooner recovery. When TCM was combined with radiotherapy, the radiation was considered to be heat toxin, which would be harmful to Yin, Qi and the transportation and transformation function of spleen and stomach. Meanwhile, Yin deficiency and blood stasis caused the syndrome of Qi deficiency and blood stasis. So the principles were tonifying Qi, nourishing Yin, promoting fluid, relieving dryness, adjusting spleen and stomach, removing heat, eliminating toxin, activating blood circulation and so on. Besides, treatments were performed according to the location of the disease and the syndromes. When TCM was combined with chemotherapy, Professor Yu held the view that the formula of tonifying spleen and replenishing kidney had the best efficacy, because the inborn and acquired state could be strengthened respectively by the method, which would improve the medullary hematopoiesis function and the immune function. In addition, empirical formula and effective commonly used Chinese herbs were concluded for the treatment of aglobulia, leucocytopenia and thrombocytopenia.
The 668 original formulas prescribed by Professor Yu in clinic were analyzed and contrasted in different angles. The rules prescribed according to the syndrome were concluded below; first, the formula of strengthening spleen and kidney should be applied all over, while the exact Chinese herbs, the dosage could be varied in terms of the conditions of the patient and the course of the disease. Second, based on the balance theory, the focus on replenishing vital energy or defending tumors was different due to the various stages. Third,19 Chinese herbs were summarized and reorganized in light of the frequency among the 179 Chinese herbs prescribed in the formulas, the intension of which could fully embody his academic theory of replenishing vital energy and defending tumors at the same time, as well as paying attention on strengthening spleen and kidney. Fourth, according to the analyses for the 19 usually used Chinese herbs, the ones with warm, moderate and sweet nature accounted for great percentage, which meant the core concept of Professor Yu was invigorating and moderate medicine. Moreover, herbs with bitter and cold nature were less commonly applied, illustrating that the method of removing heat and eliminating toxin was usually used, which was coincided with the principle of tonification and purgation in combination. Fifth, the herbs of tonification were mainly utilized, while the ones of removing heat, eliminating toxin, activating blood circulation regulating Qi were applied as assistance. Treatments performed in various aspects at the same time, such as soothing the liver, resolving hard lump, dissolving dampness and phlegm, implied the orderliness of the prescriptions. Sixth, the application of couple herbs was the essence in formulas. Seventh, the advantage in the prevention and treatment for tumors in TCM and Western Medicine could be shown in the double functions of the herbs and their widely-used values, in the evidence of TCM theory, combined with the development of pharmacological research.
Professor Yu has been engaged in clinical research on Oncology in combination of TCM and Western Medicine for more than 50 years. His academic theories and treacherous experiences about the treatment for tumors in combination of TCM and Western Medicine have been gradually formed in practice. He has been one of the founders and pacemakers on Oncology in in combination of TCM and Western Medicine, who is famous for profound knowledge, combined medicine, plenty experience and obvious efficacy home and abroad.
Objective:
First, to observe the clinical efficacy for leucocytopenia, caused by chemotherapy, by the formula of tonifying spleen and replenishing kidney, prescribed by Professor Yu; second, to discuss the advantage of tonifying spleen and replenishing kidney method for the treatment of leucocytopenia, according to the alleviation of clinical symptoms, qualities of life and T-lymphocyte subgroups, providing evidence for further study on the application of tonifying spleen and replenishing kidney method during chemotherapy.
Methods:
The random, control and prospective trials were adopted. The qualified cases were divided into treatment group and control group by the proportion of 1:1. In treatment group, the formula of tonifying spleen and replenishing kidney by Professor Yu was prescribed, while Leucogen were given in control group and the course of both treatments was two weeks. The exact efficacy of the treatment for leucocytopenia by the formula of tonifying spleen and replenishing kidney, and the alleviation of spleen deficiency syndrome and quality of life, were then evaluated, in terms of leucocyte count, integration for deficiency syndrome of spleen, scores of quality of life and T-lymphocyte subgroups.
Results:
First, the effective rates of leucocytopenia were 91% and 70% respectively in treatment group and in control group, and the difference between the groups was significant according to statistical analysis (P<0.05). Besides, the increasing range of leucocytes in treatment group was higher than that in control group, showing significant difference (P<0.05).
Second, so far as the symptom integration of spleen deficiency syndrome was concerned, the total points was decreased after treatment in both groups, showing significant difference (P<0.05). The total points after treatment and the difference value between the total points before and after treatment in the two groups was significant (P<0.05). Meanwhile, the improvement of anorexia, fatigue, abdominal distension in treatment group, was greater than that in control group.
Third, after treatment, the average KPS was higher than that in treatment group, showing statistical difference, while there was no statistical difference of the average KPS before and after treatment in control group. The improve rates of KPS were 84.4% and 53.3% respectively in treatment group and control group, showing significant difference.
Fourth, concerning T-lymphocyte subgroups, the results of CD3, CD4 and CD4/CD8 were improved after treatment in treatment group, but the difference was not significant. And there was little improvement in control group.
Fifth, in terms of side effects, the impairment of heart, liver or kidney was not observed in both groups after treatment.
Conclusions:
First, Leucocytopenia after chemotherapy can be effectively alleviated, by the method of tonifying spleen and replenishing kidney, without toxic or side effects.
Second, the symptoms of spleen deficiency syndrome after chemotherapy can be improved, and the qualities of life can be developed by the method of tonifying spleen and replenishing kidney.
我将跟师期间的病案进行整理与总结,以导师临床用药为线索,将原始处方从多个角度进行分析对比、综合归纳,以导师健脾补肾学说理论精髓为依据,总结导师应用健脾补肾学说的临证经验、用药规律(包括常用药物功效、药性、药对),发掘导师中西医结合治疗肿瘤的学术思想、理论精髓以及对临床的指导意义。并应用健脾补肾法治疗化疗后白细胞减少症32例,在症状改善、白细胞的提升,免疫功能的提高方面与对照组有明显差异,印证了郁老健脾补肾扶正理论对临床的指导意义。
在肿瘤的病因方面,郁老提出了肿瘤发病的内虚学说、失衡学说,并以平衡理论、健脾补肾法则指导肿瘤防治。郁老认为“内虚”是肿瘤发生发展的关键因素,在癌症治疗中,脏腑功能、气血功能、病邪与正气之间的平衡是病情稳定的前提。肿瘤治疗的根本原则就是平衡阴阳、扶正祛邪,使机体达到新的平衡状态。“内虚学说”指导下,健脾补肾法是最重要的扶正法则。脾肾双补,资化源,养气血,益先天,脾肾功能正常,则脏腑气血阴阳调和平衡,清浊分流,积聚消弭。
郁老是国内最早提出“益气活血法”治疗肿瘤的中西医结合专家,这一观点的确立、深入研究对全国中医治疗肿瘤的学术发展起到积极的推动作用。郁老认为气虚血瘀证在肿瘤患者中普遍存在。益气活血法治疗肿瘤最关键的问题是治疗时机、药物、用量比例的选择。凡有气虚血瘀证及放化疗期间预防治疗均可应用益气活血法；原则上是选择经现代医学研究证明有提高细胞免疫功能及增强脏腑功能的益气药为君药,活血药也选择已证明对肿瘤细胞有抑制作用的、对免疫系统功能无明显抑制的活血化瘀药。益气药的用量应大于活血药(7：3--6：4),这样才符合“气行则血行”的益气活血法的根本宗旨。如果没有有效抗肿瘤的治疗(化疗或生物靶向治疗)时,则要加上已证实有抗肿瘤作用的抗癌中草药。
在治疗上,郁老提出了中西医结合治疗肿瘤途径和方法。四原则：辨证与辨病相结合,扶正与祛邪相结合,整体与局部相结合,近期治疗与长期调摄相结合。三结合：中医药与手术相结合,与化疗相结合,与放疗相结合。
辨证与辨病治疗相结合：郁老往往将中医辨证与肿瘤自身特有的发生发展规律相结合,除了弄清楚患者目前是属于中医辨证的何种类型,了解体内气血、阴阳、脏腑虚实、经络的情况,还要清楚所患的疾病种类、病理类型、分期、侵及部位及治疗阶段等辨病的内容,根据不同疾病不同阶段的特征进行施治。在遣药处方时,注重药物的双重功能,应用中药既符合中医辨证论治的理论,又结合药物药理作用,选用具有提高免疫功能、抑瘤作用的中药。
扶正与祛邪相结合：如病属早期,正气尚未大衰,治则应重在祛邪,尽可能地利用中西医各种手段打击和消灭肿瘤,同时注意保护正气；若患者正气受损,则在祛邪同时兼以扶正。若病已属晚期,正气虚弱,已不任攻伐,特别是又无有效药物,则应以扶正为主,少佐以祛邪抗癌。手术后及放化疗后的病人以扶正调理为主,但具有高危因素的肿瘤病人易出现复发转移,宜攻补兼施。
整体与局部相结合：早期以局部治疗为主,晚期以整体治疗为主,并以局部为辅。在局部肿瘤有条件有可能清除或减灭而机体一般又能胜任者,就要设法做好局部治疗；在局部病变已无法清除或机体宿主已无法胜任的情况下,则无法做局部治疗而着重在全身整体治疗。遵循“急则治其标”的原则,如果局部病况紧急或产生严重的后果或危急时,则要紧急处理作局部治疗,同时要分清主次。
近期治疗与长期调摄相结合：近期治疗以祛邪为主要目的,西医治疗手段在取得近期疗效方面有绝对的优势,中医药治疗可以起到很好的辅助作用。运用西医方法对肿瘤病灶进行彻底的治疗以后,应用中医药方法,对机体的阴阳平衡进行及时的调整,是阻止癌症复发、转移的有效途径,防治并重,长期服药巩固疗效。
中医药与手术相结合时,手术前以中药扶正为主,益气养血,健脾补肾,增强体质,改善患者营养状况,有利于手术的进行；术后则配合中药促进机体机能的尽快康复。与放疗相结合时,针对放射线热毒之邪耗气伤阴,损伤脾胃功能,同时阴液亏耗、血行淤滞,导致气虚血瘀证。治以益气养阴,生津润燥,调理脾胃,清热解毒,活血化瘀等法则来治疗,并根据不同部位和证候辨证施治。与化疗相结合时,郁老认为以健脾补肾方药效果最好,健脾养后天,补肾益先天,对骨髓造血功能、免疫功能有很大提高,并总结出分别针对红细胞下降、白细胞下降、血小板下降的经验方及有效中草药。
我将导师临床治疗肿瘤的668张原始处方从多个角度进行分析对比、综合归纳,发掘导师“随证用药”的规律如下：(1)各种肿瘤病人的治疗均含有健脾补肾处方用药,药味、药量依据病情、治疗阶段有所不同,但健脾补肾扶正法则贯穿始终。(2)以平衡学说为指导,根据病人病情分阶段治疗,不同阶段扶正、抗癌比重均有侧重。(3)遣方用药中涉及的179味药物,根据出现频次和频率分布归纳总结了19味最为常用药物,将它们重新组合成方,充分体现了导师扶正祛邪并举、注重健脾补肾的学术思想的核心内涵。(4)常用19味中药按药性理论进行分析,性温性平味甘的药物所占比例较大,说明温补、平补是导师扶正用药的核心理念,与其提倡肿瘤治疗的“平衡理论”相符合。另外苦寒药次之,说明清热解毒是其临床祛邪的常用治法。两者相合,体现了攻补兼施的原则。(5)临床组方中扶正补虚药物为主,清热解毒药、活血化瘀药、理气药为辅,同时采用疏肝理气、软坚散结、化痰除湿治法等从多方面多层次治疗,说明导师在辨证论治基础上遣方用药,主次分明,组合有序。(6)总结导师临床常用药对,实为用药精华之所在。(7)依据中医理论选方用药,结合现代药理研究进展,重视药物的双重功用,一药多用,体现了中西医结合理论防治肿瘤的优势。
郁老从事中西医结合肿瘤临床研究五十余年,在实践中逐步形成了独特的中西医结合治疗肿瘤的学术思想和宝贵经验,是我国中西医结合肿瘤学科的奠基人和带头人之一。以其学识渊博、中西汇通、经验丰富、疗效显著而享誉海内外。
目的：
1观察郁仁存教授健脾补肾法治疗化疗后白细胞减少症的临床疗效。
2观察其对临床症状、生活质量以及T淋巴细胞亚群的改善,探讨中医健脾补肾法治疗白细胞减少症的优势,为进一步研究健脾补肾法在肿瘤化疗中的应用提供前期的依据。
方法：
本研究采用随机对照、前瞻性试验方法。将符合入组的病人按1：1的比例随机分为治疗组和对照组,治疗组采用郁仁存教授健脾补肾基础方加减,对照组应用利血生,疗程2周,以白细胞计数、脾虚症状积分、生活质量评分、T淋巴细胞亚群为观察指标,评价健脾补肾法治疗白细胞减少症的确切疗效以及脾虚症状、生活质量的改善。
结果：
1白细胞减少改善率：治疗组白细胞减少症有效率为91%,对照组有效率为70%,经统计学分析,两组有显著差异(P<0.05)。治疗组白细胞升高的幅度也高于对照组,有显著差异(P<0.05)。
2脾虚证症状积分：两组病人症状总积分治疗后较治疗前均有下降,统计学分析有显著差异(P<0.05)；两组疗后总积分及治疗前后积分差值比较有显著性差异((P<0.05)。且治疗组在食欲不振、神疲乏力、腹胀典型症状的改善方面较对照组为优。
3生活质量评分：治疗组平均KPS评分较治疗前有提高,有统计学差异；对照组治疗前后KPS评分变化无统计学差异。两组的KPS改善率分别为84.4%、53.3%,两组比较有显著差异。
4外周血T淋巴细胞亚群：治疗组CD3、CD4、CD4/CD8三者经治疗后较治疗前有提高,但无显著差异。对照组三者疗后较疗前无明显改善。
5毒副反应：两组治疗后,均未见心、肝、肾功能损害。
结论：
1应用健脾补肾法治疗可以有效改善化疗后白细胞减少症,安全无毒副反应。
2应用健脾补肾法能改善化疗病人脾虚证的中医证候,提高生活质量。
Professor Yu Rencun, a famous specialist in Oncology with combination of Traditional Chinese Medicine (TCM) and Western Medicine in China, has possessed unique academic ideology and experiences in the treatment of TCM and combination medicine for malignant tumors. I have learned much knowledge from Professor Yu by participating in the fourth experience inheritance activity. During the three years, I summarized his main academic theory, origin and development, inherited his clinical experience and unique treatment for lung cancer, gastric cancer, breast cancer, colon cancer, liver cancer and so on, accumulated a large amount of clinical cases and acquired plenty of firsthand information.
I summarized all the cases, with the basis of clinical medicine, analyzed, contrasted and concluded the original prescriptions. Based on the theory of replenishing the spleen and kidney systems form my teacher, I summarized his clinical experiences, medicine regularity, which including the efficacy, nature and pairs of the common herbs, seek his academic thinking, theoretical essence and clinical significance. Besides,32 cases of Leucocytopenia after chemotherapy were treated by tonifying spleen and replenishing kidney method, which has shown significant difference in terms of symptoms alleviation, leukocyte increase and immunologic function improvement, proving the guiding significance of Professor Yu's theory in clinic.
In terms of the etiology of tumors, Professor Yu raised the theory of inner deficiency and imbalance. He treated and prevented tumors based on the theory of balance and the method of tonifying spleen and replenishing kidney. Inner deficiency was considered to be the key reason for the ongoing and development of tumors. For treatment, the functions of Zang Fu organs, Qi and blood, as well as the balance between pathogens and vital energy were the premises with stabilization of the disease. The cardinal principle for treatment was balancing Yin and Yang, replenishing vital energy and expelling pathogens, in order to achieve new balance. Based on the theory of inner deficiency, the method of tonifying spleen and replenishing kidney was the most important principle. By strengthening the spleen and kidney, the source was plenty and Qi and blood was replenished to balance the Qi, blood, Yin and Yang, and eliminate the mass.
Professor Yu was the first expert, in the field of combined TCM and Western Medicine, who put forward the replenishing Qi and activating blood circulation methods to treat tumors, and the view had activated the development of theories for the treatment of tumors in TCM. Considering that the syndrome of Qi deficiency and blood stasis was existed among the patients with tumors, the key problem for the method of replenishing Qi and activating blood circulation was the choice of therapeutic opportunity, drugs and dosage. The method could be adopted when syndrome of Qi deficiency and blood stasis, or for the prevention and treatment during radiotherapy or chemotherapy. The herbs, with the function of replenishing Qi, proved to be develop the immunologic function and the visceral function in modern medical research, were utilized as Jun medicine on principle, while those, with the function of activating blood circulation, confirmed to restrain the tumor cells but have little suppression for immune system, were chosen as well. The dosage of herbs for replenishing Qi should more than that for activating blood circulation (7:3-6:4), to satisfy the cardinal purpose of replenishing Qi and activating blood circulation method. When effective treatment for tumors, such as chemotherapy and biologic target therapy, the herbs with the function of expel tumors should be prescribed.
For the treatment in integration of TCM and Western Medicine, Professor Yu came up with four principles and three combinations. Four principles meant the combinations of syndrome differentiation and disease differentiation, vital energy strengthening and pathogens eliminating, systemic and local treatment as well as short-term therapy and long-term healthcare, while three combinations referred to Chinese herbs with operation, chemotherapy and radiotherapy.
The combination of syndrome differentiation and disease differentiation; Professor Yu always combined syndrome differentiation with the own rule of the tumors. Apart from making sure the syndrome the patient was suffering from to know the Qi, blood, Yin, Yang, the condition of Zang Fu organs and collaterals, the classification, pathological types, stage, location and phase should also be determined. Treatment was performed according to the characteristics in different stage of various diseases. When made prescriptions, attached importance on the double functions of Chinese herbs and chose the ones, which were able to improve the immune system and suppress the tumor, according to the theories of TCM and their pharmacological actions.
The combination of vital energy strengthening and pathogens eliminating; in the early stage, when vital energy was not exhausted, the treatment of eliminating pathogens was focused on. All kinds of methods of TCM or Western medicine should be adopted to eliminate tumors and should pay attention to vital energy as well. If vital energy was decreasing, the replenishing and eliminating methods should be utilized. For the patients in the advanced stage, when vital energy was too weak to receive medicine of expelling pathogens, especially for those without effective drugs, the method of replenishing vital energy was in lead, with a small amount of herbs for expelling tumors. The method of replenishing vital energy was mainly relied on for the patients after operation, radiotherapy or chemotherapy, while combined approach of replenishment and expulsion should be given for those with high risk factors, easy to have recurrence or metastasis.
The combination of systemic and local treatment; in the early stage, local treatment was focused on while in the advanced stage, systemic treatment was predominant. Local treatment should be performed when the localized tumor could be eliminated and the patient was suitable, while systemic treatment was utilized when the localized tumor was unable to be eliminated or the patient was not suitable. If the localized condition was serious or urgent, local treatment should be performed first.
The combination of short-term therapy and long-term healthcare; Methods in Western Medicine had absolute advantage on short-term efficacy while TCM could play a supplementary role. After the complete treatment for tumor by Western Medicine, the application of TCM, which was used to adjust the balance of Yin and Yang, was an effective way to prevent recurrence or metastasis.
When TCM was combined with operation, Chinese herbs of replenishing function were mainly prescribed before the operation to strengthen Qi, nourish blood, tonify spleen and replenish kidney to strengthen the constitution, improve the patient's nutritional status and make the operation perform smoothly. While postoperative treatment principles with Chinese herbs focused on sooner recovery. When TCM was combined with radiotherapy, the radiation was considered to be heat toxin, which would be harmful to Yin, Qi and the transportation and transformation function of spleen and stomach. Meanwhile, Yin deficiency and blood stasis caused the syndrome of Qi deficiency and blood stasis. So the principles were tonifying Qi, nourishing Yin, promoting fluid, relieving dryness, adjusting spleen and stomach, removing heat, eliminating toxin, activating blood circulation and so on. Besides, treatments were performed according to the location of the disease and the syndromes. When TCM was combined with chemotherapy, Professor Yu held the view that the formula of tonifying spleen and replenishing kidney had the best efficacy, because the inborn and acquired state could be strengthened respectively by the method, which would improve the medullary hematopoiesis function and the immune function. In addition, empirical formula and effective commonly used Chinese herbs were concluded for the treatment of aglobulia, leucocytopenia and thrombocytopenia.
The 668 original formulas prescribed by Professor Yu in clinic were analyzed and contrasted in different angles. The rules prescribed according to the syndrome were concluded below; first, the formula of strengthening spleen and kidney should be applied all over, while the exact Chinese herbs, the dosage could be varied in terms of the conditions of the patient and the course of the disease. Second, based on the balance theory, the focus on replenishing vital energy or defending tumors was different due to the various stages. Third,19 Chinese herbs were summarized and reorganized in light of the frequency among the 179 Chinese herbs prescribed in the formulas, the intension of which could fully embody his academic theory of replenishing vital energy and defending tumors at the same time, as well as paying attention on strengthening spleen and kidney. Fourth, according to the analyses for the 19 usually used Chinese herbs, the ones with warm, moderate and sweet nature accounted for great percentage, which meant the core concept of Professor Yu was invigorating and moderate medicine. Moreover, herbs with bitter and cold nature were less commonly applied, illustrating that the method of removing heat and eliminating toxin was usually used, which was coincided with the principle of tonification and purgation in combination. Fifth, the herbs of tonification were mainly utilized, while the ones of removing heat, eliminating toxin, activating blood circulation regulating Qi were applied as assistance. Treatments performed in various aspects at the same time, such as soothing the liver, resolving hard lump, dissolving dampness and phlegm, implied the orderliness of the prescriptions. Sixth, the application of couple herbs was the essence in formulas. Seventh, the advantage in the prevention and treatment for tumors in TCM and Western Medicine could be shown in the double functions of the herbs and their widely-used values, in the evidence of TCM theory, combined with the development of pharmacological research.
Professor Yu has been engaged in clinical research on Oncology in combination of TCM and Western Medicine for more than 50 years. His academic theories and treacherous experiences about the treatment for tumors in combination of TCM and Western Medicine have been gradually formed in practice. He has been one of the founders and pacemakers on Oncology in in combination of TCM and Western Medicine, who is famous for profound knowledge, combined medicine, plenty experience and obvious efficacy home and abroad.
Objective:
First, to observe the clinical efficacy for leucocytopenia, caused by chemotherapy, by the formula of tonifying spleen and replenishing kidney, prescribed by Professor Yu; second, to discuss the advantage of tonifying spleen and replenishing kidney method for the treatment of leucocytopenia, according to the alleviation of clinical symptoms, qualities of life and T-lymphocyte subgroups, providing evidence for further study on the application of tonifying spleen and replenishing kidney method during chemotherapy.
Methods:
The random, control and prospective trials were adopted. The qualified cases were divided into treatment group and control group by the proportion of 1:1. In treatment group, the formula of tonifying spleen and replenishing kidney by Professor Yu was prescribed, while Leucogen were given in control group and the course of both treatments was two weeks. The exact efficacy of the treatment for leucocytopenia by the formula of tonifying spleen and replenishing kidney, and the alleviation of spleen deficiency syndrome and quality of life, were then evaluated, in terms of leucocyte count, integration for deficiency syndrome of spleen, scores of quality of life and T-lymphocyte subgroups.
Results:
First, the effective rates of leucocytopenia were 91% and 70% respectively in treatment group and in control group, and the difference between the groups was significant according to statistical analysis (P<0.05). Besides, the increasing range of leucocytes in treatment group was higher than that in control group, showing significant difference (P<0.05).
Second, so far as the symptom integration of spleen deficiency syndrome was concerned, the total points was decreased after treatment in both groups, showing significant difference (P<0.05). The total points after treatment and the difference value between the total points before and after treatment in the two groups was significant (P<0.05). Meanwhile, the improvement of anorexia, fatigue, abdominal distension in treatment group, was greater than that in control group.
Third, after treatment, the average KPS was higher than that in treatment group, showing statistical difference, while there was no statistical difference of the average KPS before and after treatment in control group. The improve rates of KPS were 84.4% and 53.3% respectively in treatment group and control group, showing significant difference.
Fourth, concerning T-lymphocyte subgroups, the results of CD3, CD4 and CD4/CD8 were improved after treatment in treatment group, but the difference was not significant. And there was little improvement in control group.
Fifth, in terms of side effects, the impairment of heart, liver or kidney was not observed in both groups after treatment.
Conclusions:
First, Leucocytopenia after chemotherapy can be effectively alleviated, by the method of tonifying spleen and replenishing kidney, without toxic or side effects.
Second, the symptoms of spleen deficiency syndrome after chemotherapy can be improved, and the qualities of life can be developed by the method of tonifying spleen and replenishing kidney.
引文
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[1]李震,仇祯绪,李军山,等.自拟补气养血方抗肿瘤机理的研究[J].实用中西医结合杂志,1997,10(3)：257-259.
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[4]田静,吴海良.益气养阴法治疗肺癌初探[J].陕西中医,2005,26(4)：344-345.
[5]熊墨年.略谈运用扶正抑癌治疗肿瘤的体会[J].实用中西医结合临床,2004,4(6)：61.
[6]张国铎.活血化瘀药抗肿瘤机理的研究进展[J].浙江中医杂志,2002,37(4)：180-182.
[7]王程,杨运高,王学良.活血化瘀经典方剂对小鼠大肠癌肝转移模型端粒酶及p53,c-erbB-2, Bcl-2基因表达的影响.第一军医大学学报,2004,21(7)：758-760.
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[10]崔娜娟,王洪琦.清热解毒中药在恶性肿瘤防治中的机理研究与应用概况[J].甘肃中医,2005,18(3)：43-44.
[11]陆付耳,李鸣真,叶望石.清热解毒治法研究的思路与方法[J].中国中西医结合杂志,2004,24(12)：1124-1129.
[12]陈泽雄,陈雯,彭俊生,等.中药复方抗癌方抑制人结肠癌细胞株端粒酶活性.中国胃肠外科杂志,1999,2(2)：147-148.
[13]孟志强,于尔辛,宋明志,等.健脾理气中药对肝癌端粒酶活性的影响.中国中医基础医学杂志,2000,6(1)：23-26.
[1]饶群阳,徐基平,刘思源,刘成高.中药复方透骨养血胶囊治疗癌症化疗后白细胞减少症51例临床观察[J].中医药导报,2010,16(6)：19.
[2]吴玉萍.芪胶升白胶囊治疗肿瘤化疗后白细胞减少症66例[J].陕西中医,2008,29(8)：1014.
[3]彭轶霞,张亚密,潘改燕.健脾益肾颗粒预防化疗后白细胞减少症的临床研究[J].湖北中医杂志,2009,31(5)：29-30.
[4]龚建益,段萍.地榆升白片预防非小细胞肺癌患者化疗后白细胞减少症的临床疗效观察[J].临床合理用药,2010,3(2)：25-26.
[5]张宇航,李要轩,李雁.复方阿胶浆对恶性肿瘤化疗后白细胞减少症的临床观察[J].中医中药.2010,17(12)：77-78.
[6]牛玉红.升阳散火汤治疗白细胞减少症80例[J].陕西中医.2008,29(6)：685-686.
[7]徐军建、闫平正.人参黄芪大枣汤治疗白细胞减少症45例[J].陕西中医学院学报,2007,30(6)：19.
[8]宋丹宁,郭焱,聂金娜,高子任.中药复方对化疗所致红白细胞减少症及免疫功能影响[J].吉林中医药,2010,30(11)：997.
[9]王淑琳,王颂平,王健.健脾益肾方治疗恶性肿瘤化放疗后白细胞减少症疗效观察[J].中国中医药信息杂志,2009,16(1)：81-82.
[10]李茂林,孙显峰.益气升白汤治疗乳腺癌化疗后白细胞减少症109例[J].陕西中医.2010,31(2)：182.
[11]田荣富,李宏斌.益气活血汤加减治疗白细胞减少症34例[J].方药应用.2010,18(6)：24.
[12]何爱国,张长富,谭瑞峰,等.生白汤治疗恶性肿瘤放化疗后白细胞减少症156例[J].中国中医药信息杂志.2006,13(10)：71-72.
[13]韩金凤,初展,王涵,等.益肾升白汤治疗恶性肿瘤化疗后白细胞减少症36例[J].河北中医.2010,32(12)：1790-1791.
[14]陈红民.生血益元煎治疗放化疗后白细胞减少症临床观察[J].现代中西医结合杂志,2009,18(2)：157.
[15]李秋荐,裴兰英,郭英昌.温和灸治疗肿瘤放化疗后白细胞减少症87例临床观察[J].江苏中医药,2007,39(1)：41.
[16]曹大明,路枚,蔡志军.扶正升白膏穴位贴敷治疗化疗后白细胞减少症60例疗效观察[J]。中华中医药杂志,2008,23(10)：941.
[17]赵喜新,路玫,等.隔姜灸治疗化疗所致白细胞减少症：多中心随机对照研究[J].中国针灸,2007,27(10)：715-720.
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[1]李震,仇祯绪,李军山,等.自拟补气养血方抗肿瘤机理的研究[J].实用中西医结合杂志,1997,10(3)：257-259.
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[3]李涌健.益气养阴法防治癌转移的实验研究[J].中西医结合学报,2004,(2)1：49-52.
[4]田静,吴海良.益气养阴法治疗肺癌初探[J].陕西中医,2005,26(4)：344-345.
[5]熊墨年.略谈运用扶正抑癌治疗肿瘤的体会[J].实用中西医结合临床,2004,4(6)：61.
[6]张国铎.活血化瘀药抗肿瘤机理的研究进展[J].浙江中医杂志,2002,37(4)：180-182.
[7]王程,杨运高,王学良.活血化瘀经典方剂对小鼠大肠癌肝转移模型端粒酶及p53,c-erbB-2, Bcl-2基因表达的影响.第一军医大学学报,2004,21(7)：758-760.
[8]佘端字.软坚散结中草药治疗恶性肿瘤研究近况[J].现代中西医结合杂志,2002,11(4)：667-669.
[9]王江东,郑广娟.燥湿化痰法治疗肿瘤机制初探[J].山东中医杂志,2002,21(7)：393-394.
[10]崔娜娟,王洪琦.清热解毒中药在恶性肿瘤防治中的机理研究与应用概况[J].甘肃中医,2005,18(3)：43-44.
[11]陆付耳,李鸣真,叶望石.清热解毒治法研究的思路与方法[J].中国中西医结合杂志,2004,24(12)：1124-1129.
[12]陈泽雄,陈雯,彭俊生,等.中药复方抗癌方抑制人结肠癌细胞株端粒酶活性.中国胃肠外科杂志,1999,2(2)：147-148.
[13]孟志强,于尔辛,宋明志,等.健脾理气中药对肝癌端粒酶活性的影响.中国中医基础医学杂志,2000,6(1)：23-26.
[1]饶群阳,徐基平,刘思源,刘成高.中药复方透骨养血胶囊治疗癌症化疗后白细胞减少症51例临床观察[J].中医药导报,2010,16(6)：19.
[2]吴玉萍.芪胶升白胶囊治疗肿瘤化疗后白细胞减少症66例[J].陕西中医,2008,29(8)：1014.
[3]彭轶霞,张亚密,潘改燕.健脾益肾颗粒预防化疗后白细胞减少症的临床研究[J].湖北中医杂志,2009,31(5)：29-30.
[4]龚建益,段萍.地榆升白片预防非小细胞肺癌患者化疗后白细胞减少症的临床疗效观察[J].临床合理用药,2010,3(2)：25-26.
[5]张宇航,李要轩,李雁.复方阿胶浆对恶性肿瘤化疗后白细胞减少症的临床观察[J].中医中药.2010,17(12)：77-78.
[6]牛玉红.升阳散火汤治疗白细胞减少症80例[J].陕西中医.2008,29(6)：685-686.
[7]徐军建、闫平正.人参黄芪大枣汤治疗白细胞减少症45例[J].陕西中医学院学报,2007,30(6)：19.
[8]宋丹宁,郭焱,聂金娜,高子任.中药复方对化疗所致红白细胞减少症及免疫功能影响[J].吉林中医药,2010,30(11)：997.
[9]王淑琳,王颂平,王健.健脾益肾方治疗恶性肿瘤化放疗后白细胞减少症疗效观察[J].中国中医药信息杂志,2009,16(1)：81-82.
[10]李茂林,孙显峰.益气升白汤治疗乳腺癌化疗后白细胞减少症109例[J].陕西中医.2010,31(2)：182.
[11]田荣富,李宏斌.益气活血汤加减治疗白细胞减少症34例[J].方药应用.2010,18(6)：24.
[12]何爱国,张长富,谭瑞峰,等.生白汤治疗恶性肿瘤放化疗后白细胞减少症156例[J].中国中医药信息杂志.2006,13(10)：71-72.
[13]韩金凤,初展,王涵,等.益肾升白汤治疗恶性肿瘤化疗后白细胞减少症36例[J].河北中医.2010,32(12)：1790-1791.
[14]陈红民.生血益元煎治疗放化疗后白细胞减少症临床观察[J].现代中西医结合杂志,2009,18(2)：157.
[15]李秋荐,裴兰英,郭英昌.温和灸治疗肿瘤放化疗后白细胞减少症87例临床观察[J].江苏中医药,2007,39(1)：41.
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