Discussion on the Comprehensive Chinese Medicine. Treatment for Postoperative Syndrome of Cancer: an

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1 32 Zhou-An Yin et al./journal of Acupuncture and Herbs 1 (2015)32-37 Discussion on the Comprehensive Chinese Medicine Treatment for Postoperative Syndrome of Cancer: an Enlightening from Xu Lao Disease Chapter in Golden Cabinet Stored Recipes Zhou-An YIN a, Ling LONG a, Chen-Yu LUO a, Yue-Xi WEN a, Zhen-Yi YUAN a* a. Hunan University of Traditional Chinese Medicine, Changsha, , China Received: September 19, 2015 Accepted: September 23, 2015 DOI: /tcm Abstract By analyzing the pathogenesis features of postoperative syndrome of cancer (PSC)in the light of traditional Chinese medicine, and by summarizing the Zhong-Jin ZHANG s principles and ideas of treatment as well as herbal and formula utilization on Xu Lao Disease (consumptive disease) in his work Golden Cabinet Stored Recipes, combining with our own experience, to elucidate the basic processing principles of traditional Chinese medicine for postoperative syndrome of cancer. Keywords: Xu Lao Disease,Postoperative syndrome of cancer, Zi Gan Cao Decoction Though a lot of advancement has been achieved in recent years, the traditional operation, chemotherapy and radiotherapy are still the most used and effective methods for tumor. However, those conventional ways also bring series of side effects, such as in blood system:blood cells reduction even aplastic anemia; digestive system:loss of appetite, vomitting and nausea, stool changes (constipation or loose stool); cardiovascular system: palpitation (arrhythmias like atrial premature or myocardial damage), lower limbs thrombosis; endocrine system: spontaneous or night sweats, insomnia, decreasd libido, menstrual disturbance, importance and premature ejaculation; personality changes, depression, etc. For the convenience of discussion, we name all those clinical manifestations as postoperative syndrome of cancer (PSC). The treatments of PSC are directly related to *Corresponding author. Professor. Postgraduate supervisor. Director of Hunan provincial key TCM course "TCM formulas" and director of the teaching team. address: physical recovery, quality of life and long-term survival rate. Traditional Chinese medicine has accumulated abundant experience on PSC treatment. Its concepts of individualized and comprehensive treatments have been recognized broadly by peers. In our clinical practice, we found that the pathogenesis and manifestations of PSC were amazingly in accordance with the Xu Lao Disease which was recorded in Golden Cabinet Stored Recipes by Zhong-Jing ZHANG. We tried to treat the PSC by the same process to Xu Lao Disease and achieved very good effects. We hereby summarize our experience as follows: 1 Similar pathogenesis between PSC and Xu Lao Disease To a TCM viewpoint, operation, chemotherapy and radiotherapy are sort of removing evil treatments. Due to the side effects mentioned above, those treatments can better be the last resorts. Although it trends to have "microoperation", "targeted treatment", PSC: postoperative syndrome of cancer

2 Zhou-An Yin et al./journalofacupunctureandherbs1 (2015) "local chemotherapy", "local radiotherapy" in tumor treatments, it still inevitablely harms the body healthy parts like Qi, blood, Jin and Ye (body fluid), plus severe side effects above mentioned, it can finally lead to spleen and stomach, liver and kidney function failure or even loss. To the viewpoint of Chinese medicine, the basic five types of substances (Qi, blood, Jin, Ye and Jing) have been injuried, in a short term the body can manifest multiple "deficiency" signs of the five Zang organ systems- this is the core pathogenesis of PSC. Similarly, the five basic substance in deficiency is also the basic pathogenesis of Xu Lao Disease by the viewpoint of Zhong-Jing ZHANG. Therefore, to study and summarize ZHANG's experience on Xu Lao Disease is undoubtedly good for clinical process of PSC. 2. What we could learn from Zhong-Jing's thoughts on Xu Lao Disease 2.1 Comprehensive regulation of Shen, Qi and Xing By Zhong-Jing's way, there are three layers for treating Xu Lao Disease: regulating Shen (spiritual layer), regulating Qi (energy layer) and regulating Xing (physical layer),with decreased order of priority. For instance, "female intersection in dream", "feeling weakness and upset so sleepless", "anxious heat in limbs" have reflected manifestations such as "restless in mind" and "frustration in emotions" in patients with Xu Lao Disease. The emotional changes in tumor patients are very common due to concern to the disease prognosis, economic burden, recurrence, etc. As mentioned in the Yellow Emperor's Inner Classics, "Heart is the manager of all organ systems. If the manager works well, the other organs will work well as well, otherwise the other organs can be in danger". Therefore, to postoperative patients, the number one important thing is to establish their confidence for fighting with disease. Except for good doctor-patient communication and appropriate psychological counseling, "regulating Shen" in the herbal formula is also very important. In Zhong-Jing's formulas, the Suan Zao Ren Decoction, Gui Zhi Jia Long Gu Mu Li Decoction, and Bai He Series, Zhi Zi Chi Series, Chai Hu Series could be always chosen for regulating heart and Shen. Those formulas have been deemed to have effects of improving emotions and sleeping. Secondly, the major manifestations of Xu Lao patients are related to decreased "Qi Transition" function, or in other words, decreased organ functions. For instance, if the spleen and stomach function get low, Qi cannot flow up and down properly so the patient will have poor appetite, loose stool or "deficient constipation", dizziness, fatigue, spontaneous sweat, easy to catch cold, etc. If the function of kidney in charge of water and essence decrease, the patient will have "deficient lower back pain", "not fluent urination", "loss of sperm", etc. An important Zhong-Jing's strategy is to regulate Qi to restore the organ functions.for instance, Xiao Jian Zhong Decoction works by recovering the "cultivation and transition" function of spleen and stomach; Shen Qi Pill works by recovering the "Qi transition and water flowing" function of kidney. Zhi Gan Cao Decoction works by generally promoting all the five types of basic substances in the five-zang organ systems. Therefore, to treat the PSC, we need first of all actively recovering the organ functions. Except for Huang Qi Jian Zhong Decoction, Shen Qi Pill, Ban Xia Xie Xin Decoction, Gui Zhi Gan Cao Decoction, Mai Meng Dong Decoction and Zhi Gan Cao Decoction in Zhong-Jing's books, the other formula in later generations such as Liu Jun Zi Decoction, Shi Quan Da Bu Decoction, Bu Zhong Yi Qi Decoction, Modified Fu Mai Decoction, and so on can also be chosen. Besides regulating Shen and Qi, Zhong-Jing also paid attention on "regulating Xing", which means, to remove the excessive part or evil part. Typical cases are using Da Huang Zhe Chong Pill to treat "Gan Xue Lao"(dry blood consumption by direct translation based on its clinical manifestations, including but not limited tuberculosis); and using "Ta Gan Powder" to treat "cold tuberculosis", "ghost staying so whole

3 34 Zhou-An Yin et al./journalofacupunctureandherbs1 (2015)32-37 family infected". This means "specific formula for specific disease" by according to specific cause. After operation, chemotherapy or radiotherapy, it is unreasonable to think that the patient is "tumor free", so to the remaining tumor, we could adapt Zhong-Jing's experience, adding "regulating Xing" to "regulating Shen" and "regulating Qi". Clinically, this means to add more herbs which can remove phlegm, activate blood flow and disperse congestion to the formula. Da Huang Zhe Chong Pill can therefore be chosen for treating liver cancer, ovary cancer which thought to be in the scope of "Gan Xue Lao". There were not so many herbs of removing phlegm or dispersing congestion being mentioned in Zhong-Jing's books, but in later generations, some famous formulas such as Dao Tan Decoction, Xiao Luo Pill can be good candidates. Herbs like Nan Xing (Arisaematis Erubescentis Rhizoma), Ban Xia(Pinelliae Rhizoma), Bei Mu (Fritillariae Cirrhosae Bulbus), Tian Kui Zi(Semiaquilegiae Radix), Bai Jie Zi (Brassicae Junceae Semen), Mu Li (Ostreae Concha), Hai Zao(Sargassum), Gua Lou(Trichosanthis Kirilowii Fructus et Semen), Zhu Li(Phyllostachys nigra(lodd.)), can be chosen based on pathopattern differentiation. All those are important strategies for "regulating Xing". 2.2 Qi, Blood, Jin, Ye and Jing being regulated together with five-zang organs, especially concentrating on spleen and stomach The formation of Xu Lao Disease has involved the deficiency of Qi, blood, Jin, Ye and Jing, and the decreased function of five-zang organ systems, so Zhong-Jing paid more attention on cultivating those substances and promoting five-zang organ functions while treating Xu Lao Disease. From the composition of Zhi Gan Cao Decoction, we can see how it works: in the formula Zhong-Jing used the high dosage of Sheng Di(Rehmanniae Radix), assisted with Mai Dong(Ophiopogonis Radix), Ma Ren(Cannabis Fructus), A Jiao(Asini Corii Colla) and Da Zao(Jujubae Fructus) to cultivate blood and Yin; Ren Shen(Ginseng Radix), Zhi Gan Cao(Radix Glycyrrhizae Preparata), Gui Zhi(Cinnamomi Ramulus), Sheng Jiang(Zingiberis Recens Rhizoma) to promote Qi and Yang; Ren Shen(Ginseng Radix), A Jiao(Asini Corii Colla) and Shu Di(Rehmannia glutinosa) can also cultivate Jing, so the whole formula has taken care of all above-mentioned substances. From the angle of five-zang organs, Mai Dong(Ophiopogonis Radix), Sheng Jiang(Zingiberis Recens Rhizoma) enter the Lung, Ma Ren(Cannabis Fructus), Shen Di(Rehmanniae Radix), A Jiao(Asini Corii Colla) supplement liver blood and Jing; Ren Shen(Ginseng Radix) can strongly tonify the original Qi, entering the kidney, spleen and lung meridians; Zhi Gan Cao(Radix Glycyrrhizae Preparata),Sheng Jiang(Zingiberis Recens Rhizoma) and Da Zao(Jujubae Fructus) are a common composition that Zhong-Jing used for regulating and strengthening spleen and stomach; Gui Zhi(Cinnamomi Ramulus) and Gan Cao(Glycyrrhiizae Radix) compose the "Gui Zhi Gan Cao Decoction" which enters the heart meridian, spicy and sweet together to generate Yang and Qi to stop palpitation and arrhythmia. Zhi Gan Cao Decoction is therefore the typical model for regulating five-zang organs, adopted broadly by later generations. The authors, based on the specific principles and pathogenesis of PSC in specific stage, are keen on using this formula to deal with multiple symptoms such as blood cells decrease, fatigue and palpitation, insomnia and dreams, "deficient constipation", hair loss, cancer pain, and peripheral blood vessel disease (thrombosis). Our efforts have achieved promising effects. This is what we benefit from Zhong-Jing's thoughts on Xu Lao Disease. While regulating the five substances and five-zang organs, Zhong-Jing had set the highest priority to spleen and stomach since they are the origin of five substances. Multiple formulas used for treating Xu Lao Disease, such as Xiao Jian Zhong Decoction, Huang Qi Jian Zhong Decoction, Gui Zhi Jia Long Gu Mu Li Decoction, Zhi Gan Cao Decoction, were modified from Gui Zhi Decoction. And we know, Gui Zhi Decoction is the recognized "ancestor formula" for regulating spleen and stomach and cultivating Qi and blood as well as Yin and Yang. In the formula the Sheng Jiang(Zingiberis Recens Rhizoma), Da Zao(Jujubae Fructus), Yi Tang(Saccharum Granorum), Ren

4 Zhou-An Yin et al./journalofacupunctureandherbs1 (2015) Shen(Ginseng Radix) and Zhi Gan Cao(Radix Glycyrrhizae Preparata) are common used herbs for strengthening spleen and stomach. Therefore, the authors very commonly to deal with PSC by reference to Zhong-Jing's idea, to regulate spleen and stomach, by which the postnatal part can be strengthened. We combine diet recipe and herbs, to doubly benefit the spleen and stomach. We once treated a patient Ding with gastric lymphoma, after operation and chemotherapy, her body weight went down from 45kg to 25kg in three months. This is so-call "complete loss of big muscles", in western medicine cachexia. The patient had a lot of symptoms such as fatigue, fear of wind, difficult for eating and drinking, loss of hair, palpitation, menstruation disappear, we grasped the disease root of spleen and stomach and persisted using small dose of Gui Zhi Decoction and its modifications: plus Bai Shao(Paeoniae Alba Radix) for abdominal pain, this is Gui Zhi Jia Shao Yao Decoction; plus Huang Qi(Scutellariae Baicalensis Radix) for fatigue and short breath, this is Huang Qi Jian Zhong Decoction; plus Long Gu(Apatite) and Mu Li(Ostreae Concha) for sweat, this is Gui Zhi Jia Long Gu Mu Li Decoction; plus warm gruel and covering thick quilt for cold, this is taking from the original method in Zhong- Jing's books; plus Ge Gen(Puerariae Lobatae Radix) for neck swollen or pain, this is Gui Zhi Jia Ge Gen Decoction; Small dosage of Wen Jing Decoction if the patient has dysmenorrhea, and so on. By such kind of treatment combining with diet recipes (more meals per day but less for each) for one year more, the patient has gradually taken her body weight back and had menstruation again, the other symptoms also gradually disappeared. So far she has survived for 7 years, with no cancer recurrence and high quality of life. 2.3Differentiate the chronic and acute states and disease severity, and choose corresponding herbs and formula Zhong-Jing has clear awareness in treating chronic and acute states, "if a chronic disease adding acute state, we should treat the acute state first, then the chronic disease". While dealing with acute state, we still need to take care of chronic disease. For Xu Lao Disease, Zhong-Jing usually treated the acute state based on consideration of chronic disease: while patients lost sperm or blood, he used Gui Zhi Decoction for the deficient root, but also used high doses of Long Gu(Apatite) and Mu Li(Ostreae Concha) to withdraw sperm and blood; while patient had "diarrhea", "palpitation", "abdominal pain", he doubled the Shao Yao(Paeoniae Alba Radix), added Yi Tang(Saccharum Granorum) to treat the acute symptoms, but kept Xiao Jian Zhong Decoction for the old chronic disease. To PSC patients, due to the specific body constitutions they are more easily to catch superficial pathopattern (cold/fever), coughing (with infection), so Gui Zhi Decoction or Chai Hu Decoction could be selected, or Shen Su Liquid, Xing Su Powder in later generations can also be chosen. Ma Huang Series should be avoided. If patients have irregular menstruation, such as early period, menstruation quantity changes, dysmenorrhea, or prolonged period, metrorrhagia, Huang Qi Jian Zhong Decoction, Zhi Gan Cao Decoction, or Huang Tu Decoction can be chosen, but formula with strong bitter or cold natures should be avoided. According to the disease conditions (mild, severe, chronic, acute, etc.), Zhong-Jing chose formula styles by a different way. In general, if the patient had acute and severe state, Zhong-Jing usually chose decoction and powder; if the patient had mild state, then pills would be used for a chronic improvement. For instance, Zhi Gan Cao Decoction was used for "fatigue and deficiency, sweat and upset in chest, retarded and occasional break pulse sort of emergency"; Shu Yu Pill was used for "all kinds of deficiency and fatigue, ailments induced by wind"; Da Huang Zhe Chong Pill was used for "dry blood consumption" manifested as "extremely fatigue and thin". By considering the severe blood stasis inside, he used Shui Zhi and Qi Cao to strongly remove blood stasis, but put those strong herbs in pill to avoid to harm the healthy Qi, this is so-called "supplement deficiency by a slow way". Zhong-Jing's way was a good reference for dealing with multiple symptoms and complications after operation of cancer. Some breast cancer or thyroid cancer patients, after operation or chemotherapy they had severe metrorrhagia, which was really emergent, the authors has prescribed high dose of Zhi Gan Cao Decoction

5 36 Zhou-An Yin et al./journalofacupunctureandherbs1 (2015)32-37 plus Long Gu(Apatite), Mu Li(Ostreae Concha) and Xian He Cao(Agrimoniae Herba), cooked to a high concentration and asked the patients drinking frequently. Several patients have been cured so they avoided to cut the uterus. After operation, if the patients had peripheral thrombosis in lower limbs, this is socalled "Tuo Ju", "Mai Bi" in Chinese medicine. We usually use high dose of Zhi Gan Cao Decoction, delivering Shui Zhi(Hirude nipponica Whitman) and Pao Jia(Manis temminckii) powder, 2-3g, bid. This is also coming from Zhong-Jing's idea that using Da Huang(Rhei Palmati Radix et Rhizoma)and Zhe Chong(Eupolyphaga Seu Steleophaga) to remove severe blood stasis. Some patient therefore avoided to cut limbs. 3. Process to common disease and symptoms after operation in cancer patients 3.1 Decrease of blood cells: we usually process it as normal Xu Lao disease, so the first choice would be Zhi Gan Cao Decoction, or Huang Qi Jian Zhong Decoction, or Dang Gui Jian Zhong Decoction by increasing the dose of Da Zao(Jujubae Fructus), or plus A Jiao(Asini Corii Colla) to supplement blood, or plus Bu Gu Zhi(Fructus Psoraleae), Gou Qi Zi(Lycii Fructus)to promote kidney essence. 3.2 Vomiting and constipation(deficient type): normal vomiting or constipation (deficient nature), without phlegm, dampness or water retaining, can still be treated as Xu Lao disease. We need not treat the symptom itself, but better to use Zhi Gan Cao Decoction directly. After taking the Zhi Gan Cao Decoction, the patient's Yin blood or Yang Qi can be balanced so the bowel movement will automatically recover. Strong laxatives such as Cheng Qi Series should absolutely avoided. After the symptoms relieved, He Jian Liu Jun Zi Decoction should be used for further regulation. 3.3 Palpitation, insomnia and sweat: they are common seen after chemotherapy. Atrial premature beats is very common. It's related to the Qi, blood, Yin and Yang deficiency in heart. Gui Zhi Gan Cao Decoction 15-20g can be a common choice. Else like Gui Zhi Gan Cao plus Long Gu Mu Li Decoction, or Zhi Gan Cao Decoction can also be used. For mild insomnia, Suan Zao Ren Decoction can be used; severe one Zhi Gan Cao Decoction replacing Ma Ren with Suan Zao Ren. For sweat, Gui Zhi plus Long Gu Mu Li Decoction would be the first choice, or even adding Suan Zao Ren(Ziziphi Spinosae Semen), Fu Xiao Mai(Fructus Tritici Levis) to the original formula. If the sweat is a hot type, then we can replace Gui Zhi(Cinnamomi Ramulus) with Huang Qin(Scutellariae Baicalensis Radix) in the Gui Zhi plus Long Gu Mu Li Decoction (named by the author Huang Qin Long Gu Mu Li Decoction), adding Suan Zao Ren(Ziziphi Spinosae Semen) can be always effective. Further, Bai He (Lili Virduli Bulbus) can also be added to make gruel for assistant treatment. 3.4 Disturbed menstruation: after operation, female patients may have menstruation disturbance, early or delayed menstruation, decreased or increased quantity, prolonged period, or metrorrhagia,which could be treated by routine treatments of "menstruational diseases", but by consideration of the specific state after operation (Qi cannot control blood), we usually use Huang Qi Jian Zhong Decoction, or Dang Gui Jian Zhong Decoction, or Zhi Gan Cao Decoction and their modified formulas. If the patient has dysmenorrhea deficient cold with stagnation type, Wen Jing Decoction is preferred. If the patient has severe bleeding, or prolonged period, some withdrawal or hemostatic herbs such as Xian He Cao(Agrimoniae Herba), Long Gu(Apatite), Mu Li(Ostreae Concha) and A Jiao(Asini Corii Colla) should be added. 3.5 Aphthous: Aphthous is a common symptom after tumor operation. Though it is a small ailment, it can affect eating and patient's emotion by recurrence. The most common clinical pathopattern is Yin deficiency. Gan Lu Yin, San Cai Feng Sui Dan and Zhi Gan Cao Decoction can be used, wherein the Gan Cao(Glycyrrhiizae Radix) can be doubled the dose, or even plus Ren Zhong Huang(Homo sapiens). Modern researches have shown that Gan Cao(Glycyrrhiizae Radix) has good effect on repair of mucosa, so it was

6 Zhou-An Yin et al./journalofacupunctureandherbs1 (2015) entitled "mucous membrane repair agent". 3.6 caner pain: cancer pain is a common symptom in advanced cancers. It affects the patient's quality of life severely. Common used medications in modern medicine such as non-steroidal analgesics, pethidine, Bucinperazine, tramadol, morphine, can induce peptic ulcer, vomiting and constipation, or addiction, or drug resistance, or suppression of breath so should try to avoid if not necessary. In the view of Chinese medicine, "lack of nutrition in certain area is one of the causes of pain", so to strongly supplement Qi and blood can be helpful for relieve the pain. We have observed that Zhi Gan Cao Decoction can relieve cancer pain in certain extent. This can be related to the increased pain tolerance. Some sedative herbs like Suan Zao Ren(Ziziphi Spinosae Semen), Yuan Zhi(Polygalae Radix) and Yan Hu Suo(Corydalis Yanhusuo Rhizoma) can also be added for pain suppression. To summarize, multiple manifestations of PSC suggest that PSC should be considered as Xu Lao Disease and being treated by principles and ideas of Zhong-Jing on Xu Lao Disease. From our experience, this has achieved promising effects, but need to be further confirmed by peers in practice. Competing interests The authors declare that they have no competing interests. Acknowledgements This research was supported by the Hunan provincial level funding project- key subject development of TCM formulas. The authors would also thank contribution of the whole research and teaching team in the university. References No.

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