Summary on Professor QIAO Bao-zhang's Experience in Syndrome Differentiation and Treatment for Pancreatic Cancer

ZHANG Qi-man (张琦曼), ZHENG Jin (郑 瑾)

1. Shaanxi University of Chinese Medicine, Xianyang 712000, China

2. Tangdu Hospital of Air Force Medical University, Xi'an 710038, China

ABSTRACT Objective:To summarize clinical experience of Professor QIAO Bao-zhang in treatment for pancreatic cancer, and to provide reference for clinicians. Methods:Through learning from Professor QIAO during his clinical practice and listening to his lectures, Professor QIAO Bao-zhang's clinically proved cases of treating pancreatic cancer based on syndrome differentiation were organized and summarized.From aspects like etiology, pathogenesis, treatment principles and treatment methods of pancreatic cancer,Professor QIAO's experience in diagnosis and treatment for this disease was analyzed and explored,and characteristics of medication were summarized. Two typical cases were selected as proof, and his treatment ideas and methods were explored. Results:Professor QIAO believes that the pathogenesis is mostly deficiency of vital Qi (正气), and stagnation of phlegm, heat and dampness in Zang-Fu (脏腑)and meridians. Around intermingled deficiency and excess, syndrome differentiation and treatment were performed. Due to treatment methods such as strengthening vital Qi to eliminate pathogenic factor, clearing heat, eliminating dampness and resolving phlegm, as well as removing toxicity and resolving hard mass,progress of malignant tumors was inhibited and recurrence and metastasis of malignant tumors were delayed. Conclusion:Professor QIAO's experience in treating pancreatic cancer is worth learning.

KEYWORDS QIAO Bao-zhang; Pancreatic cancer; Syndrome differentiation and treatment; Medical record; Famous doctor's experience

INTRODUCTION OF PROFESSOR QIAO BAO-ZHANG

Professor QIAO Bao-zhang was a member of China Association of Chinese Medicine, and vice president of Shaanxi Provincial Society of Chinese Medicine. Currently he serves as the chairman of Working Committee for Inheritance of Academic Experience of Famous Traditional Chinese Medicine Practitioners of Shaanxi Provincial Society of Chinese Medicine, and an adjunct professor at Tangdu Hospital of Air Force Medical University. He used to engage in teaching, scientific research and medical treatment at Shaanxi University of Chinese Medicine. Through studying, clinical practice, relearning, and re-practice, he continued to deepen and improve his cognition on classic theories in traditional Chinese medicine (TCM). He emphasizes treating diseases based on differentiating constitutions, performing treatment in accordance of individuals, and combination of studying and treating. He is good at treating various intractable diseases of internal medicine such as malignant tumors. The author of this paper is fortunate to learn from Professor QIAO during his clinical practice and has benefited a lot. Two typical cases of diagnosis and treatment for pancreatic cancer are reported in this paper, and Professor QIAO's ideas on syndrome differentiation and treatment and treatment experience were explored and analyzed to provide reference for colleagues.

GENERALIZATION ON ETIOLOGY AND PATHOGENESIS OF PANCREATIC CANCER

Pancreatic cancer is one of the digestive system tumors with extremely high malignancy,hidden early onset, rapid disease progression, short overall survival and poor prognosis. In recent years,the morbidity and mortality have been on the rise,and the 5-year survival rate is only 6%[1,2]. Because of its insidious onset, it is often in the late stage when it is diagnosed[3]. In TCM, there is no direct description of "pancreatic cancer", but according to clinical manifestations of pancreatic cancer, such as abdominal pain, jaundice, weight loss and poor appetite, pancreatic cancer can be classified as"abdominal mass" "abdominal pain" "jaundice" and so on[4]. In ancient medical books,Five Changes of Miraculous Pivot(《灵枢•五变篇》) records, "People who have abdominal mass in the intestine... If the gastrointestinal function is poor, pathogenic Qi (邪气) will stay in it, and abdominal mass will occur."At the same time, ancient medical books also contain descriptions of etiology and pathogenesis of pancreatic cancer.General Treatise on Causes and Manifestations of All Diseases(《诸病源候论》) records, "Abdominal mass is caused by disharmony of Yin (阴) and Yang (阳), weakness of Zang-Fu (脏腑)... fighting with Qi of Zang-Fu."Jingyue's Complete Works(《景岳全书》) records, "For disease of abdominal mass, food and drink... wind and cold, all of them can lead to it."

Professor QIAO Bao-zhang believes that for patients with pancreatic cancer, insufficiency of congenital Qi, being worn with age, chronic illness, improper diet, seven emotions, six climatic exopathogens or other factors lead to imbalance of Yin and Yang, phlegm coagulation and blood stasis, as well as filling of cancer toxin, causing biased constitutions and stasis and obstruction in Zang-Fu viscera and meridians, eventually forming abdominal mass. Deficiency of vital Qi manifests as deficiency of Yin, Yang, Qi and blood, or deficiency of one of them, or deficiency of some of them. Excess of pathogens manifests as toxins of exogenous pathogens, toxins of emotions, toxins of pathological products, a severe toxin of one of them, or mixed toxins of many of them. Among them, vital Qi injury is the key to the onset of this disease. pathogenic toxins stay and accumulate in the body, Qi and blood circulate abnormally,and deficient Qi fails to promote normal circulation of blood, causing pathological products such as phlegm, heat and blood stasis to stay in Zang-Fu and meridians. The two pathogenic factors struggle with each other, and the condition is lingering and difficult to heal. On the whole, it manifests as intermingling of cold and heat, superficies and interior, as well as deficiency and excess, and even worse, it manifests as a critical phenomenon of "divorce of Yin and Yang". Locally, stasis in meridians manifests as feeling oppressed and discomfort, pain, and lumps. At the same time,according to the theory of visceral manifestations in the theoretical system of TCM, combined with physiological and anatomical characteristics of the pancreas, the pancreas belongs to Six-Fu, and being prone to generating dampness and heat is its pathological feature[5]. Therefore, Professor QIAO combines the above understanding and long-term clinical experience and believes that deficiency of vital Qi, and stagnation of phlegm, dampness and blood stasis are the main pathogenesis of pancreatic cancer.

LAWS IN SYNDROME DIFFERENTIATION AND TREATMENT AND CHARACTERISTICS IN MEDICATION FOR PANCREATIC CANCER

Based on the generalization of the etiology and pathogenesis of pancreatic cancer, Professor QIAO adopts the academic idea of "consolidating body resistance and clearing the source" to systematically organize the corresponding TCM syndrome differentiation theoretical system. Here,"consolidating body resistance" refers to improving deficiency syndromes of patients, and "clearing the source" refers to removing excess syndromes of cancer. Patients with pancreatic cancer can be divided into 3 stages: early, middle and late, but most patients with pancreatic cancer are found to be in the late stage, and they all have different degrees of Qi deficiency. In the early stage, vital Qi is strong pathogenic factors are mild. At this time, the patient's overall resistance is adequate.Diagnosis and treatment generally focus on overcoming pathogenic toxins, and treatment methods are promoting blood circulation for removing blood stasis as well as removing toxicity,complemented by strengthening vital Qi. In the middle stage, pathogenic Qi is gradually rising, and vital Qi is gradually weak. At this time, reinforcement and elimination in combination should be used,and attention should be paid to protecting spleen and stomach when combating toxins. Therefore,supplementing spleen Qi is the key to strengthening vital Qi and supplementing deficiency. During this time, Professor QIAO often usesRadix Codonopsis,Radix Ginseng Rubra,Radix Astragali seu Hedysari,Rhizoma Atractylodis Macrocephalaestir-fried with bran, andPoria to supplementQi and invigorate spleen. For those with long term Qi deficiency accompanied by different levels of Yin deficiency, so considered additions ofRadix Rehmanniae Recens,Radix Paeoniae Alba,Rhizoma Polygonatistewed with Chinese rice wine andRadix Ophiopogonisis made to nourish Yin and blood. At the same time,Radix Bupleuriis added to promote Qi movement(气机), andFructus Aurantii Immaturusis used to remove food stagnation, which helps spleen transportation. For those with mild blood stasis,medicines for activating Qi flowing and promoting blood circulation such asRhizoma Cyperi,Radix Aucklandiae,Radix Curcumae, etc. are often added.For those with severe blood stasis,Pseudobulbus Cremastrae seu Pleiones,Rhizoma SparganiiandRhizoma Curcumaeare added as appropriate to break blood circulation for removing blood stasis,as well as eliminate mass. At the same time, the insect medicine ofEupolyphaga Seu Steleophagaand vinegarCarapax Trionycisare added to remove toxicity for resolving hard mass and eliminating carbuncles, entering the Liver Channel directly to the focus of disease. For dampness-heat patients,Herba Artemisiae Scopariae,Fructus Gardeniae,Radix Scutellariae, etc. are added for promoting bile flow and diuresis. In learning from Professor QIAO, it was found that on the basis of general medicines for promoting Qi, activating blood circulation, eliminating phlegm, removing dampness, clearing heat and strengthening vital Qi, when adding Chinese materia medica such asRadix Actinidiae,Herba Euphoribiae HelioscopiaeandHerba Scutellariae Barbatae,anti-cancer efficacy will be revealed. In clinical practice, it is found that Professor QIAO likes to use the medicine of Herba Euphoribiae Helioscopiae recorded inShen-nong's Classic of Materia Medica(《神农本草经》). Professor QIAO believes thatHerba Euphoribiae Helioscopiaeis bitter in flavor and slightly cold in property, and functions in inducing diuresis for removing edema, resolving phlegm and hard mass, etc.. In vivo and in vitro experiments[6,7], it was found thatHerba Euphoribiae Helioscopiaehas an anti-tumor effect. Its main mechanism is achieved by restraining growth and proliferation of tumor cells, suppressing cell activity,regulating inhibited genes, and inhibiting tumor blood vessel formation, etc. through multi-channel and multi-target coordination. In the late stage of pancreatic cancer, the patient often looks dull with dark complexion, low voice and weak respiration.The course of disease is prolonged, and pathogens are excessive when vital Qi is weak. During this period, it is necessary to mainly strengthen vital Qi to bank up the origin, regulating and supplementing Qi, blood, Yin and Yang, accompanied by eliminating the pathogens, so as to prolong the survival of the patient. In addition, eliminating or reducing undesirable stimulating factors is helpful to efficacy.

EXAMPLES OF PROVED CASES

Case 1: Mr. (Mrs.) ZHANG, 75 years old,married. The patient was diagnosed as pancreatic cancer when coming to visit. Chief complaint:Epigastric hitting pain had lasted for more than half a year, which could be relieved by moving around. The patient ate less but slept well, with normal urination and defecation. The tongue was dark red with a thin, white and moist coating, and the pulse was deep on the left and slippery on the right. At the beginning of 2020, the local hospital treated as "atrophic gastritis", and the symptoms were relieved to some extent. One month later, the patient was significantly thinner, accompanied by upper abdomen and back pain and discomfort. On May 8, 2020, he visited the outpatient department of gastroenterology in Tangdu Hospital of Air Force Medical University. The CT enhanced scan showed weak enhancement area in the neck and body of the pancreas, considering malignant lesions, pancreatic cancer followed by pancreatic body tail atrophy and pancreatic duct dilation. Diagnosis: pancreatic cancer. TCM diagnosis: abdominal mass, with the syndrome of intermingled phlegm and blood stasis. Treatment methods: resolving hard mass,activating blood circulation and resolving phlegm.Free decocting granules of Chinese materia medica were prescribed:Rhizoma Pinelliae Preparata15 g,Radix Astragali seu Hedysari20 g,Rhizoma Coptidis9 g,Fructus Trichosanthis20 g,Semen Coicis20 g,Fructus Aurantii Immaturus12 g,Rhizoma Cyperi10 g,Ramulus Cinnamomi10 g,Faeces Togopteri10 g,Poria10 g,Cortex Magnoliae Officinalis10 g,Herba Euphoribiae Helioscopiae10 g andPericarpium Citri Reticulatae6 g. Seven sets, taken after mixing each set with boiling water, and one set per day. Subsequent visit on May 19, 2020: mental improvement, pain relief, frequent urination at night,dry stools, normal appetite, sound sleep, a pale red tongue with a thin white fur, a slippery pulse which was deep on the right. Based on the above prescription,Herba Lobeliae Chinensis15 g,Semen Arecae10 g andRadix Linderae10 g were added.Seven sets, taken after mixing each set with boiling water, and one set per day. After that, the patient comes to visit every month and has been followed up till now.

Note: The spleen and stomach are located in the middle-Jiao (中焦), responsible for transportation and transformation. The tumor had consumed healthy Qi for a long time when the patient came to see the doctor. It hurt the spleen and stomach, and the source of food and drink essence was lacking. Therefore, less appetite and weight loss were seen. Qi deficiency failed to promote blood circulation, leading to impediments of blood flow. Plus, the spleen is the source of generating phlegm. Since weakness of the spleen and stomach, abnormal transportation and distribution of body fluid, dampness was accumulated to form phlegm. Phlegm and blood stasis intermingled with each other and stopped under the heart, then the stoppage caused pain.After moving around, circulation of Qi, blood and body fluid was accelerated, and the stoppage was relieved, so the pain was also relieved. Blood stasis in vessels led to the dark red tongue. Xiao Xian Xiong Decoction (小陷胸汤) and Erchen Decoction(二陈汤) were applied as the basic prescription.Rhizoma Pinelliae PreparataandPericarpium Citri Reticulataewere used to promote Qi and resolve phlegm,Fructus Trichosanthiswas used to loosen the chest and resolve hard mass, andRhizoma Coptidiswas used to clear heat, altogether playing the effect of resolving phlegm and hard mass.Fructus Aurantii Immaturuswith Cortex Magnoliae Officinaliswere used for promoting Qi, dissipating distension and eliminating fullness;Radix Astragali seu Hedysariwas used for regulating lung and spleen deficiency, as well as strengthening vital Qi and eliminating pathogenic factors; andHerba Euphoribiae Helioscopiaewas used for dissipating phlegm, resolving hard mass and defeating cancer.Rhizoma CyperiandFaeces Togopteriwere used as assistance to regulate Qi movement, and activate blood circulation for removing blood stasis. They have effects of promoting Qi and relieving pain. It was in accordance with the idea of supplementing Qi, invigorating spleen and eliminating dampness by usingSemen CoicisandPoria.Ramulus Cinnamomiwas also used to warm meridians due to its dispersing pungent flavor. During the second visit, the patient's pain was relieved, appetite was improved, but the urination was frequent at night,and there were dry stools. On the basis of the previous prescription,Semen Arecaewas added for pungency dispersing and bitter discharging,removing stagnation, gently relaxing bowels;Radix Linderaewas used for promoting Qi and reducing urination, as well as warming kidney and dispelling cold, andHerba Lobeliae Chinensiswas for used enhancing effects of dispelling blood stasis and fighting cancer.

Case 2: Mr. Shi, 70 years old, male, married.The patient was diagnosed as abdominal cavity metastasis after pancreatic cancer surgery. The chief complaint was 7 months after the surgery of pancreatic head cancer. Symptoms were slight or severe pain at the left side of the navel, difficult to fall asleep at night, less appetite, regular urination and defecation, a pale red tongue with a yellowish coating, and a stringy and weak pulse. The patient visited Tangdu Hospital of Air Force Medical University on April 2019, and was diagnosed as pancreatic space occupation. On April 16, 2019,he was given "resection of the tail of pancreatic body, splenectomy and partial gastrectomy" under general anesthesia. Pathology after the surgery showed pancreatic moderately differentiated adenocarcinoma, and locally moderate-to-poorly differentiated adenocarcinoma. Re-examination of abdominal enhanced CT at the end of October 2019 revealed multiple metastases in the abdominal cavity. Postoperative pathology showed abdominal mass and fibrous tissue metastatic poorly differentiated adenocarcinoma, suggesting the origin of abdominal cavity. On November 6,2019, chemotherapy of Gemcitabine combined with Tegafur, Gimeracil and Oteracil Potassium Capsules was continued. TCM diagnosis: abdominal mass, with the syndrome of disharmony of liver and spleen, and deficiency of both Qi and Yin.Treatment methods: dispersing stagnated liver Qi,invigorating spleen and regulating stomach, as well as clearing heat, nourishing Yin and cooling blood. Free decocting granules of Chinese materia medica were prescribed:Radix Rehmanniae Recens20 g,Rhizoma Polygonatistewed with Chinese rice wine 20 g,Ramulus Euonymi15 g,Radix Angelicae Sinensis10 g,Radix Ophiopogonis10 g,Radix Paeoniae Alba10 g,Herba Dendrobii10 g,Radix Salviae Miltiorrhizae20 g,Fructus Aurantii Immaturus12 g,Concha Ostreae20 g,Herba Artemisiae Annuae15 g, vinegar Carapax Trionycis20 g,Herba Euphoribiae Helioscopiae10 g andEupolyphaga Seu Steleophaga10 g.Seven sets, taken after mixing each set with boiling water, and one set per day. Re-examination on December 10, 2019: The pain was relieved, and stomach discomfort was improved, with sound sleep at night, gradually increased appetite, regular urination and defecation, fatigue, aversion to cold,a pale red tongue with a slightly yellow coating, and a large pulse. Based on the previous prescription,Radix Astragali seu Hedysari20 g andHerba Lobeliae Chinensis20 g were added. Twenty sets,taken after mixing each set with boiling water, and one set per day. After the medication, the patient's pain was significantly relieved, mental condition and physical strength were significantly improved, all symptoms were improved, and the quality of life was improved. Follow-ups have been lasted so far.

Note: The patient was an elderly man with pancreatic head cancer accompanied by abdominal metastasis after surgery. Pancreatic cancer has an insidious onset and develops rapidly, has a high degree of malignancy, and has a poor prognosis.At the first diagnosis, the patient was injured by the cancer and the surgery, and the patient was at an advanced age, so that the disease was in the late stage, with injured spleen and stomach. The spleen failed to ascend and stomach Qi failed to descend, leading to abnormal transportation and transformation as well as Qi movement, so that clear Yang failing to ascend, emptiness of marrow sea and malnutrition of spirit and orifices caused insomnia. Spleen deficiency leads to being restricted by wood. As the pivot of transportation and transformation, liver Qi invading spleen manifested as symptoms like less appetite and fatigue. Spleen deficiency is prone to produce dampness, and long-term stagnation of dampness leads to heat generation. So, it manifested as a slightly yellow coating. Spleen deficiency gradually became worse,Qi, blood and body fluid were depleted, and vascular filling was insufficient, so the pulse was weak when being pressed heavily.Radix Rehmanniae Recens,Radix Ophiopogonis,Rhizoma Polygonatistewed with Chinese rice wine, andHerba Dendrobiiwere applied for supplementing Qi, nourishing Yin and stimulating his appetite.Radix Angelicae SinensiswithRadix Paeoniae Albawere used for supplementing liver blood, astringing Yin and relieving pain.Ramulus EuonymiandRadix Salviae Miltiorrhizaewere used for clearing dryness-heat in Yin phase, and had the power of cooling blood.Concha Ostreae indicated tranquillization with heavy prescription. In addition,Herba Artemisiae Annuaeshould be used withCarapax Trionycisto nourish Yin and clear heat. WU Ju-tong said, "Carapax Trionyciscannot enter Yang alone, but it can be led byHerba Artemisiae Annuae'', making Yang enter Yin to sleep soundly[8].Fructus Aurantii Immaturuswas used as assistance for bitter discharging and pungency dispersing, breaking Qi and eliminating distention, as well as eliminating and removing food stagnation, which could help spleen transportation.Herba Euphoribiae Helioscopiaewas used for eliminating phlegm, dissipating hard mass and fighting against cancer. For such diseases with complex etiology, insect medicines like Scorpio andEupolyphaga Seu Steleophaga[9-11]can be used to achieve effects of removing toxicity and resolving hard mass, promoting blood circulation for removing blood stasis, as well as calming endogenous wind and relieving pain. Plus, the insect medicines prefer wandering, entering the Liver Channel,unblocking meridians, and directly reaching the focus of disease. This kind of medicines belongs to "medicines for nourishing essence and blood",which often play the role of "channel ushering" and achieve the effect of getting twice the result with half the effort. During the second visit, the pain was relieved, the appetite was increased, and the sleep was improved, but the patient was still fatigued. On the basis of the previous prescription, Professor QIAO prescribed Radix Astragali seu Hedysari to dispel pathogenic factors and strengthen vital Qi, accompanied by Herba Lobeliae Chinensis for removing toxicity, dissipating blood stasis and fighting against cancer.

CONCLUSION

Professor QIAO believes that man is an organic whole. In order to achieve the state of "Yin being at peace and Yang being compact leading to essencespirit being normal", it is necessary to follow balance of Yin and Yang, regular diet and daily life, and being of good mood, so as to maximize the realization of the idea of preventive treatment of disease[12].

In advanced malignant tumors, the etiology and pathogenesis are complex and changeable. In the past experience in treating pancreatic cancer,HE Ren, a national TCM master[13], and Professor LIU Shen-lin[14]used TCM in the treatment of pancreatic cancer, which was subtle with significant efficacy. Although treatment methods of doctors are different, there are similarities among them.Professor QIAO Bao-zhang believes that TCM has its specific advantages in treating tumors, and it is necessary to correctly understand the role of TCM in the process of tumor treatment. According to inspection, auscultation and olfaction, inquiry, pulse taking and palpation, comprehensive analysis on data gained by four diagnostic methods, he performs comprehensive syndrome differentiation on the patient's disease location and nature of disease.Especially for patients with advanced tumors,after the prolonged illness, failure of treatment,mistreatment, or radiotherapy, chemotherapy,surgery and other treatment, vital Qi is inevitably consumed. Although vital Qi and pathogenic factors coexist, it is mainly deficiency of vital Qi. Insufficient vital Qi is the internal factor that produces cancer.Development of the cancer further attacks vital Qi.In prevention and treatment of cancer, it is always necessary to "strengthen vital Qi". Starting from the early, middle and late stages of tumors, the early stage of cancer mildly damages vital Qi, and various pathological states are not significant. The treatment is mainly fighting against cancer and striving for a radical cure. In the middle stage, both strengthening vital Qi and fighting against cancer should be given consideration to, thereby achieving long-term survival with tumors. In the late stage, it is mainly strengthening vital Qi, and fighting against cancer is supplemented to prolong life. Retrospective studies have shown that[15,16]although TCM plays an irreplaceable role in the treatment of cancer,it must also be combined with western medical treatment methods such as surgery, chemotherapy and radiotherapy to improve patients' quality of life after surgery and when bearing tumors, inhibiting tumor recurrence and metastasis, and extending the life cycle of tumor patients. Professor QIAO repeatedly emphasized that due to complexity of the etiology during each stage of pancreatic cancer, in clinical treatment, the basic contradictory changes of pancreatic cancer should be grasped from disease differentiation and treatment. Do not try to be quick. Patients' symptoms, signs,tongue coating and pulse manifestations need to be repeatedly considered. The patients' quality of life can only be improved by accurate syndrome differentiation, precise medication, starting from the overall disease and considering its treatment methods.