The Study On Tcm Syndromes Of Oxapliplatin-induced Peripheral Neuropathy In Patients With Colorectal Cancer

Objective:In this study,we collected the clinical data of patients with colorectal cancer who had peripheral neuropathy induced by oxapliplatin based chemotherapy to know the essential characters of these patients more clearly by clustering analysis,sum up characteristics and type distribution of TCM syndromes of this disease,explore its correlation with neurotoxicity grade.This is conducive to improving the theoretical basis of TCM treatment of peripheral neurotoxicity caused by oxaliplatin,improving the standardization of TCM dialectical treatment,promoting the closer combination of TCM theory and current clinical practice,enriching the connotation of TCM with The Times,and contributing to the inheritance and development of TCM.Methods:A total of 100 cases of colorectal cancer patients with oxapliplatin-induced grade 1 or above peripheral neuropathy were collected,including name,gender,age and other general information,TNM stage,peripheral neurotoxicity grade,four TCM diagnosing contents of current symptoms and signs,and related syndromes of the disease syndrome list were recorded by basic information questionnaire,four diagnosis information table and syndrome element table after signing the informed consent.We refered to the "simplified measurement" method involved in "syndrome differentiation" to determine the syndrome element and the information was quantified into Excel and imported into SPSS25.0statistical software for statistical analysis.According to the analysis results,the TCM syndrome characteristics of oxaliplatin induced peripheral neurotoxicity in CRC patients were summarized,and the classification of TCM syndrome types of this disease was summarized by cluster analysis,and the correlation between it and the grade of neurotoxicity was explored.Results:1.A total of 100 colorectal cancer patients with peripheral neurotoxicity treated with oxaliplatin were included,including 52 males(52%)and 48 females(48%),with a male-to-female ratio of 1.08:1.All the subjects ranged from 27 to 84 years old,with an average age of 62.11 years.Among them,46(46%)people aged "61-70" accounted for the highest proportion.The number of persons aged over 60 includes 61(61%).The neurotoxicity grade was mainly in grade Ⅱ,accounting for 42%,followed by grade I and Ⅲ,22 cases(22%)and 21 cases(21%),respectively.The neurotoxicity grade Ⅳ was less,15cases(15%).TNM stage Ⅱ-Ⅳ were included,with 20 patients(20%)in stage Ⅱ,39 patients(39%)in stage Ⅲ,and 41 patients(41%)in stage Ⅳ.There was no significant difference in the distribution of neurotoxicity grading between male and female(P>0.05).There was no significant difference in TNM staging between males and females(P> 0.05).2.According to the four diagnostic information,30% or higher frequency syndromes in patients with oxapliplatin-induced peripheral neuropathy include finger sisal,cold aggravation,toes hemp,lustreless,numbness of the skin,tiredness,form angular,inanition,hand numbness,loose stools,unwillingness to speak,bodily pain,melanochroous,hemafecia,nausea and vomiting,stool slenderness,forgetfulness,shortness of breath,abdominal distension,numbness in the legs,cough,mucus in stool,spontaneous sweating,pain refusing to pressure,stabbing pain,night pain,anorexia.Tongue elephant proportion with the faint red tongue,purple dark tongue,fat tongue ranks the top.Tongue coating was mainly thin tongue coating,lubricate tongue coating and white tongue coating.The categories of fine pulse,deep pulse and astringent pulse accounted for a higher proportion in pulse condition.3.Disease location factors in OIPN patients were mainly spleen,meridians and large intestine,and the main disease factors were blood stasis,qi deficiency,Yang deficiency,phlegm and blood deficiency,followed by cold,dampness,qi stagnation,fluid deficiency and Yin deficiency.Syndrome factor skin,muscles and bones,dynamic wind,Yang hyperactivity appeared less.The syndrome elements of spleen,large intestine and Qi deficiency all held the dominant proportion in different stages of the disease.The frequency of meridians,coldness,phlegm and blood stasis in stage Ⅱ and Ⅲ was significantly more prominent than that in stage Ⅳ.Compared with stage Ⅱ and Ⅲ,the location of disease of liver and kidney increased,and the disease elements of Qi deficiency,Yang deficiency,blood deficiency and Yin deficiency assumed an increasing tendency.It manifests both deficiency and sthenia syndrome in stage Ⅱ and Ⅲ of the disease,and gradually turn into deficiency syndrome in stage Ⅳ.The distribution of the nature of disease such as dynamic wind,Yang hyperactivity,skin,muscles and bones were less,which had little correlation with this disease.There was no significant difference in the distribution of the location and the nature of disease among different neurotoxicity grades(P>0.05).In other words,according to the frequency statistics,spleen,meridians and large intestine were the main disease location factors,while blood stasis,qi deficiency,Yang deficiency,phlegm and blood deficiency were the main disease factors in the different neurotoxicity grade.4.Five types of syndrome were calculated by cluster analysis: We selected symptoms accounting for more than 10% which collected from 100 patients,including 62 items,6kinds of tongue,6 kinds of coating on the tongue and 7 kinds of pulse condition of system for cluster analysis.Based on traditional Chinese medicine diagnostics technique and cluster analysis data,Five types of syndrome were calculated with a reference line for 22.467 location which consist of the blood stasis obstruction,qi and blood deficiency,yang deficiency and blood stagnation,the Yin deficiency of liver and renal,and Spleen-deficiency and phlegm-turbid stagnation were listed as 29 cases(29%),27 cases(27%),17 cases(17%),14 cases(14%),and 13 cases(13%).There was no statistical difference in gender and TNM stage distribution among the five TCM syndromes(P>0.05).The distribution of TCM syndromes in OIPN patients at different ages had significant differences(P<0.05).There was statistical significance in syndromes distribution among different neurotoxicity grades(P<0.05).Compared with grade I neurotoxicity,grade Ⅱ neurotoxicity had statistically significant difference in the distribution of syndromes(P<0.05),while grade Ⅲ and Ⅳ neurotoxicity had not.(P>0.05;P> 0.05).Compared with grade Ⅱ neurotoxic syndrome distribution,there was statistical significance between grade Ⅲ and grade Ⅳ(P<0.05;P <0.05).There was no statistical significance in the distribution of grade Ⅲ and Ⅳ neurotoxic syndromes(P>0.05).Conclusion:1.The OIPN was a unique adverse reaction after the application of L-OHP in adjuvant or palliative chemotherapy for colorectal cancer treatment.In addition to the absolute symptoms of skin and limb numbness,patients presented with frequent loose stools,diarrhea,stool slenderness,pus and blood in stools and other related symptoms of colorectal cancer.That finger sisal,cold aggravation,toes hemp,lustreless,numbness of the skin,tiredness,form angular,inanition,hand numbness,loose stools,unwillingness to speak,bodily pain,melanochroous,hemafecia,nausea and vomiting,stool slenderness,forgetfulness,shortness of breath,abdominal distension,numbness in the legs,cough,mucus in stool,spontaneous sweating,pain refusing to pressure,stabbing pain,night pain,anorexia were main syndrome of the disease.Tongue elephants were mainly red,purple,fat and large tongue.Tongue coating was mainly thin tongue coating,lubricate tongue coating and white tongue coating.Thin,heavy and astringent pulses were common.Different cases had corresponding features for different syndrome.2.Disease location factors in OIPN patients were mainly spleen,meridians and large intestine,and the main disease factors were blood stasis,qi deficiency,Yang deficiency,phlegm and blood deficiency,followed by cold,dampness and Qi stagnation.In stage Ⅱ and Ⅲ patients,the location factors were situated predominately in the meridians,colludals and spleen,and the disease elements were mainly blood stasis and Qi deficiency.In patients of stage Ⅳ,Yang deficiency,qi deficiency and blood deficiency were more common.The frequency of meridians,blood stasis,cold and phlegm in stage Ⅱ and Ⅲ was more prominent than that in the late stage.The factors of liver and kidney in the late stage of the disease increased,and the factors of deficiency of fluid,deficiency of Yang,deficiency of blood and deficiency of Yin showed an upward trend.It manifests both deficiency and sthenia syndrome in stage Ⅱ and Ⅲ of the disease,and gradually turn to deficiency syndrome in stage Ⅳ.3.Cluster analysis was used to obtain five TCM syndrome types: the blood stasis obstruction,qi and blood deficiency,yang deficiency and blood stagnation,the Yin deficiency of liver and renal,and Spleen-deficiency and phlegm-turbid stagnation.There were differences in the distribution of syndromes in different age groups.the blood stasis obstruction syndromes were common syndrome at most of the middle-aged and young people.The incidence of yang deficiency and blood stagnation increased with age.There were also differences in the distribution of TCM syndromes with different grades of neurotoxicity.The distribution of syndromes in grade I neurotoxicity was mainly blood stasis obstruction while grade Ⅱ and Ⅲ neurotoxicity was also obvious with blood stasis obstruction,yang deficiency and blood stagnation,qi and blood deficiency,with relatively deep disease position and more obvious deficiency.The distribution of syndromes in grade Ⅳ neurotoxicity was more deficiency than sthenia syndrome which was more obvious with the prolongation of the course of disease.