Risk Factors And Characteristics Of Traditional Chinese Medicine(TCM) Syndrome For Chemotherapy-induced Nausea And Vomiting(CINV) Based On Literature And Clinical Evidences

Objective This study was aiming to standardize and sort out characteristics of traditional Chinese Medicine(TCM)syndrome and symptoms for chemotherapy-induced nausea and vomiting(CINV)based on literature and clinical evidences.And attempted to analyze the CINV TCM syndromes of different chemotherapy regimens,types and severity.Meanwhile,further researches would be developed to inquire the risk factors of CINV by means of clinical features recorded.Methods 1.Review of the literature For this review,we searched Chinese database,such as CNKI,WANFANG DATA,VIP,and Sino Med from database inception to February 20,2020.As well,the published literature and books of TCM oncology.CINV TCM syndromes were sorted out and the major indexes were analyzed using SPSS 21.0 and SPSS Modeler 18.0 for relevance.2.Clinical research All the data were collected including the baseline data,disease data,other data and physical and laboratory tests of the patients.The online CINV assessment tool was used to assess the chemotherapy emetogenicity level and risk of patient emetogenicity.Degree of nausea /vomiting and Quality of FLIE were assessed by Functional Living Index Emesis(FLIE)questionnaire MASCC antiemesis tool(MAT)on Day2 and Day6.Meanwhile,the duration of CINV was also recorded from beginning to end.Following assessment of CINV,TCM signs and symptoms of CINV patients were collected by TCM symptom-rating scales.TCM syndrome differentiation was summarized according to the results of part one,which was also analyzed through several aspects such as chemotherapy regimens,types and severity of CINV.And the risk factors of CINV were identified.Statistical significance was analyzed using SPSS 21.0 and SPSS Modeler 18.0 software.Results 1.Literature research(1)Published books: A total of 30 published books on oncology of TCM and integrated TCM and western medicine were included,and 47 records of TCM syndrome types were collected,covering 12 kinds of TCM syndromes after standardization.These are Syndrome of deficiency of stomach yin(weiyinxu-zheng,WYXZ,14.89%),Syndrome of heat in stomach(weire-zheng,WRZ,14.89%),Syndrome of incoordination between liver and stomach(ganqifanwe-izheng,GQFWZ,12.77%),Syndrome of deficiency of spleen qi(piqixu-zheng,PQXZ,12.77%),Syndrome of cold pathogen attacking stomach(weihan-zheng,WHZ,8.51%),Syndrome of dampness stagnancy due to spleen deficiency(shikunpiweizheng,SKPWZ,8.51%),Syndrome of phlegm-dampness blocking stomach(tanyinneizu-zheng,TYNZZ,8.51%),Syndrome of deficiency of spleen yang(piyangxu-zheng,PYXZ,8.51%),Syndrome of retention of food in stomach(shizhipiwei-zheng,SZPWZ,4.26%),and other few syndromes.A grand total of 6 disease syndrome elements were summarized,chiefly involving stomach,spleen,liver and gallbladder.And 13 kinds of pathological nature,the excess elements included dampness(shi),qi-stagnation(qi-zhi,QZ),retention of food(shiji,SJ),fire/heat(huo/re,HR),and the deficient elements included yang deficiency(yangxu,YX),qi deficiency(qi-xu,QX),blood deficiency(xue-xu,XX).The syndrome elements with strong correlation were "QZ-dampness ","QZ-spleen","dampnessspleen","dampness-YX",“YX-spleen”,"QZ-liver","QX-dampness" and "QXspleen".(2)Periodical category: 18 studies were included,involving 1503 cases and 68 records of CINV TCM syndrome were refined,which were SKPWZ(22.1%),PQXZ(13.2%),TYNZZ(11.8%),WYXZ(11.8%),syndrome of dampness-heat in spleen and stomach(piweishire-zheng,PWSRZ,8.8%),GQFWZ(7.4%),PYXZ(4.4%),WRZ(4.4%),SZPWZ(2.9%),WHZ(2.9%).A grand total of 9 disease syndrome elements were summarized,mainly involving spleen,stomach,liver and gallbladder,half-superficies and half-interior.And 16 kinds of pathological nature,the excess elements mainly included QZ,dampness,phlegm,HR,and the deficient elements mainly included QX,YX,XX,yin deficiency(yin-xu,Y-X).The syndrome elements with strong correlation were "QZ-stomach ","QX-spleen"," stomach-spleen","dampness-spleen","dampness-stomach","QZ-dampness".There were 5 studies of platinum-containing CINV,involving 425 cases,mainly included PWSRZ,SKPWZ,and PQXZ.The disease was mainly located in the spleen and stomach,and the disease nature were mainly dampness,QZ,QX,phlegm,SJ and YX.2.Risk factors of CINV Of 107 patients enrolled in this study,83(77.6%)were occurred of CINV,and 24 had confirmed acute nausea,13 cases of acute vomiting,79 cases of delayed nausea and 29 cases of delayed vomiting.82(76.6%)cases were occurred of nausea,including 20 cases of grade 1(24.4%),53 cases of grade 2(64.6%)and 9 cases of grade 3(3.7%).30(28.3%)cases were occurred of vomiting,including 18 cases of grade 1(60.0%),9 cases of grade 2(30.0%),3 cases of grade 3(10.0%)and 0 cases of grade 4(0.0%).(1)Occurrence of CINV Women were at a higher risk of occurrence than men,especially in women less than 50 years old.The incidence of CINV was higher in patients with motion sickness and expectation.Also,patients educated with primary school and below or university and above were at a higher risk of CINV.Meanwhile,patients with lower height,weight,body surface area and lower levels of erythrocyte,blood glucose,albumin and total protein were at higher risk of CINV than others,which were significant(P < 0.05).The result also showed that infection of helicobacter pylori(Hp),age from 51 to 60 years old,and expectation were independent risk factors for the occurrence of CINV.(2)Severity of CINV There was a significant negative correlation between KPS and the overall severity of CINV.And patients with HP,morning sickness history,and stage III in clinical were at heavier severity of CINV.The difference was statistically significant(P < 0.05).(3)Type of CINV The incidence of acute CINV in patients with gynecological malignancy was lower,and both of acute and delayed CINV in patients with expectation occurred significantly higher than others(P < 0.05).In addition,the incidence of delayed CINV was higher in female,and patients of primary school and below.And patients with motion sickness occurred more in delayed CINV,especially nausea,the differences were statistically significant(P < 0.05).Besides,the incidence of delayed vomiting was higher in patients with Hp and primary chemotherapy,and the differences were statistically significant(P < 0.05).There was a significant positive correlation between heart rate and acute nausea.There was also a significant positive correlation between BMI and acute vomiting.Besides,a significant negative correlation between KPS and delayed nausea was found.The results showed that patients with Hp infection and no drinking history who had lower level of education were at a heavier severity of delayed nausea.And delayed vomiting was more severe in female and patients with stage III or no distant metastasis.The differences were significant(P < 0.05).Furthermore,the duration of CINV in patients with no drinking history was significantly longer(P < 0.05).3.Results of CINV TCM syndrome(1)Symptoms: 97 TCM symptoms of CINV were sorted out.Most of the patients were accompanied by different degrees of loss of appetite,fatigue,insomnia,constipation and other symptoms.Tongue manifestation was chiefly red or pink togue with white or greasy fur,and stringy slippery pulse was common.(2)Syndrome elements: A grand total of 6 disease syndrome elements were summarized,mainly involving spleen,stomach,liver,gallbladder and heart.15 disease syndrome elements,dampness,qi stagnation,food accumulation and phlegm,and deficiency syndrome mainly qi deficiency,yang deficiency,blood deficiency and yin deficiency.And 15 kinds of pathological nature,the excess elements mainly included dampness,QZ,SJ,phlegm,and the deficient elements mainly included QX,YX,XX and Y-X.(3)TCM syndrome: 122 syndrome records were obtained by standardization.According to the frequency,they were SKPWZ(46.7%),WYXZ(16.4%),PQXZ(11.5%),PYXZ(8.2%),GQFWZ(6.6%),TYNZZ(5.7%),and SZPWZ(4.9%).4.Characteristics of CINV TCM syndrome(1)Severity of CINV The degree of CINV in patients with GQFWZ was the heaviest and SZPWZ was the slightest,the difference was statistically significant(P< 0.05).When involved in liver,gallbladder,heart and mind,as well as disease nature of XX,QZ and SJ,the degree of CINV was more severe.Patients with a course of above 15 days had a higher proportion involved in heart.And patients with a course of less than15 days had a higher proportion involved in XX and SJ.There was no significant difference in the different grades of nausea and vomiting.(2)Type of CINV SKPWZ was the main syndrome of each CINV type.The disease location of acute CINV was mainly in spleen,stomach,liver,gallbladder,half-superficies and half-interior,while that of delayed CINV was mainly in spleen,stomach,liver,heart and gallbladder.The pathological nature of nausea was dampness,QX,YX,QZ,while that of vomiting was SJ,dampness,QZ,QX.In delayed nausea,the degree of WYXZ and SKPWZ was more severe,and the degree of GQFWZ was slightest.In acute vomiting,the degree of GQFWZ and SZPWZ was severe,while the degree of WYXZ was mild.In delayed vomiting,SZPWZ,SKPWZ and WYXZ were more severe.Besides,PQXZ and PYXZ were mild in all types.And the differences were statistically significant(P < 0.05).Acute CINV was more severe,when the disease location involved in halfsuperficies and half-interior,gallbladder,liver.Delay CINV was more severe,when the disease location involved in heart and mind.And delay nausea was more severe,when the disease location involved in liver,gallbladder and intestine.The patients with YX,XX,QZ,SJ and HR had a heavier acute nausea.And the degree of delay nausea was more severe in patients with Y-X,XX,SJ and qi sinking(qixian,QS).The patients with QZ and SJ had a heavier acute vomiting.And the degree of delay vomiting was more severe in patients with QZ,SJ and QS.All the differences were statistically significant(P<0.05).(3)Other factors Surprisingly,virous chemotherapy regimens,gender,Hp infection motion sickness and other factors play great roles of the characteristic of TCM syndrome.Conclusions(1)CINV TCM syndrome mainly consisted of SKPWZ,PQXZ,TYNZZ,WYXZ,GQFWZ,PYXZ and SZPWZ.The disease location was spleen,stomach,liver,gallbladder and heart.And the pathological nature centered of dampness,QZ,QX,YX and Y-X.(2)The characteristics of CINV TCM syndrome in different types and degrees had diversities.Virous chemotherapy regimens,gender,Hp infection and other factors play great roles of the characteristic of TCM syndrome.(3)There were many risk factors related the occurrence and progress of CINV,such as female,less than 60 years old,motion sickness,no drinking history,Hp infection,morning sickness history,expectation,sleep debt,innutrition,low KPS,advanced malignancy and other factors,which also affect the characteristic of TCM syndrome,and deserved further research to indicate.(4)Few previous studies had investigated CINV TCM syndrome,lack of unified syndrome standards and guidelines consensus.Further researches with large sample,multi-center and rigorous design are needed to account for it.It is necessary to establish and improve the specific TCM syndrome and consensus for CINV.