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大肠癌中医证候相关因子的多因素分析研究
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摘要
目的:
     本研究通过对大肠癌晚期疾病中医证候相关因子的多因素进行流行学病调查分析研究,了解大肠癌晚期疾病的中医证候分布规律和特点,并分析了舌象特点,及与证候之间的相互关系,着重探讨大肠癌晚期疾病的证候构成,分析归纳中医病因病机特点,为临床更好的对大肠癌疾病进行辨证论治提供理论依据,同时也为中医证候的客观化、量化研究提供新的研究途径。
     方法:
     研究对象:病例来源:2011年1月至2011年12月在广州中医药大学第一附属医院一、二、三、四肿瘤科住院的大肠癌晚期患者100例,男52例,女48例。收集其中医临床症状、体征、实验室指标等。采用横断临床流行病学调查研究方法,将符合研究标准的患者纳入研究对象。病例选择标准:大肠癌西医诊断标准,参照中华人民共和国政务司编著的《新编常见恶性肿瘤诊治规范》中结直肠癌的诊断标准。临床分期标准采用国际公认的TNM分期。中医辨证标准参照《中药新药临床研究指导原则》、《中医临床诊断术语证候部分》、《临床中医肿瘤学》及《中医诊断学》五版教材(修订版)辨证部分,整理出瘀毒蕴结证、脾肾阳虚证、大肠湿热证、气血两虚证、肝肾阴虚证五种主要证型。舌诊部分参看《中医诊断学》五版教材(修订版)舌诊部分内容。统计学处理:调查结束后,所有调查资料汇总,输入计算机,用excel表格建立数据库,进行数据管理,用SPSS16.0软件进行统计分析。对患者相关指标等进行统计分析、比较。对患者进行舌象,中医证候分析。统计方法:分类资料用x2检验,多样本均数比较用方差分析,组间多样本比较采用q检验,中医临床症状分析及舌象分析采用样本聚类分析及探索性因子分析方法。统计分析后,初步得出大肠癌晚期疾病的证候诊断重要指标、证型类型、主要临床症状、舌象特点及流行病学特点。
     结果:
     一、临床描述性分析
     被调查的100例大肠癌晚期患者所出现的临床症状中,腹泻出现频率最高,共76例,约占(76.0%)。其次为腹内结块,共70例(70.0%)。其他出现频率较高(≥50%)的临床症状有神疲乏力、食少纳呆、粘液脓血便、消瘦、腹胀、少气懒言、腰膝酸软、小便短赤。舌质表现中,齿痕舌(40.0%)、暗红舌(34.0%)、胖大舌(33.0%)、是出现频率较高的舌质特征;舌苔以薄白苔、黄腻苔为主各29例(29.0%),其次为薄黄苔23例(23.0%);而舌下络脉研究中有91例(91.0%)的患者出现舌下络脉有密网状小血管改变,76例(76.O%)患者舌下络脉主干长度大于3/5,62例(62.0%)患者舌下络脉饱满隆起,轻度弯曲或局限曲张,舌下络脉颜色青紫59例,占59.0%。脉象中脉涩所占比例较大,占34例(34.0%),其次为脉滑数23例(23.0%)。
     二、临床证型研究
     根据聚类分析结果,结合专家意见,提示出大肠癌晚期患者证型聚为五类较合理,分别为瘀毒蕴结证,脾肾阳虚证,气血两虚证,大肠湿热证,肝肾阴虚证。其中瘀毒蕴结证、脾肾阳虚证出现频率最高,其次为大肠湿热证、肝肾阴虚证、气血两虚证。瘀毒蕴结证主要症状为:腹内肿块坚硬、腹内结块、粘液脓血便、腹泻、口唇紫暗、面色晦暗、便色紫暗、肌肤甲错、小便短赤、消瘦、神疲乏力、腹部刺痛、里急后重、口中粘腻,舌脉主要有舌下络脉有密网状小血管、脉涩、舌下络脉色紫黑、舌下络脉主干长度大于3/5、舌质暗红、瘀点舌、舌下络脉宽度2mm~2.6mm、舌下络脉弥漫曲张等。大肠湿热证主要症状为:粘液脓血便、里急后重、口渴、小便短赤、腹部阵痛、肢体困重、.口干咽燥、肛门灼热、失眠、腹泻、口苦、腹胀、食少纳呆、口中粘腻、烦躁易怒、胸闷等。舌脉主要有脉滑数、黄腻苔、舌下络脉有密网状小血管、主干长度大于3/5、红舌、舌下脉络色青紫、饱满隆起、轻度弯曲、舌下络脉局限曲张。脾肾阳虚证主要症状为:腹部隐痛、畏寒肢冷、神疲乏力、腹泻、少气懒言、食少纳呆、口淡无味、舌下络脉饱满隆起,轻度弯曲、唇甲色淡、头晕目眩、完谷不化、腹内结块、气短、腰膝酸软、消瘦、腹胀。舌脉主要有舌下络脉有密网状小血管、局限曲张,舌下络脉色青紫、薄白苔、淡白舌、胖大舌、齿痕舌、舌下络脉主干长度大于3/5、宽度2mm~2.6mm、脉沉细。气血两虚证主要症状为:头晕目眩、腹胀、腰膝酸软、食少纳呆、便色紫暗、粘液脓血便、畏寒肢冷、唇甲色淡、里急后重、腹泻、自汗、气短、面色萎黄、腹部刺痛、肿块坚硬、腹内结块、肢体浮肿等,舌脉主要有舌下络脉局限曲张、有密网状小血管、主干长度小于3/5、舌下络脉青紫、饱满隆起,轻度弯曲、瘀点舌、淡暗舌、脉沉细、脉涩、舌下络脉宽度2mm~2.6mm、舌下络脉色紫黑、薄黄苔、齿痕舌等。肝肾阴虚证主要症状为:失眠、腰膝酸软、口干咽燥、腹部隐痛、腹内结块、五心烦热、口渴、消瘦、腹胀、小便短赤、神疲乏力、大便干结、头晕目眩、烦躁易怒、少气懒言、便秘、耳鸣、心悸、胸闷、面色晦暗、盗汗、颧红、口唇紫暗、口苦、肛门坠胀、唇甲色淡等。舌脉主要有舌下络脉主干长度大于3/5、脉弦细数、舌下络脉有密网状小血管、瘦小舌、剥苔、绛舌、红舌、舌下络脉饱满隆起,轻度弯曲、舌下络脉宽度2mm~2.6mm、薄黄苔等。
     本次调查的大肠癌晚期患者病理类型以腺癌居多,尤其是中分化管状腺癌(90.0%),各证型间病理类型比较无明显差异。
     三、证与舌的相关研究
     大肠癌晚期患者舌象的研究中,舌象呈以下特点,在100例的研究对象中,暗红舌34例、淡白舌26例、淡红舌5例、红舌20例、绛舌6例、青紫舌2例、淡暗舌7例。其中淡白舌、暗红舌、红舌所占比重较重,尤以暗红舌所占比重最重。其中瘀毒蕴结证以暗红舌、瘀点舌、瘀斑舌为主;大肠湿热证以红舌为主;脾肾阳虚证以淡红舌、淡白舌为主;气血两虚证以淡白舌、淡暗舌为主,肝肾阴虚证以暗红舌、绛舌、红舌为主。在100例研究对象中,薄白苔29例、黄腻苔29例、薄黄苔23例、黄厚苔8例、剥苔7例、白润苔6例、白腻苔1例、白厚苔1例。其中瘀毒蕴结证以以薄黄苔、黄腻苔、黄厚苔为主;大肠湿热证以黄腻苔为主;脾肾阳虚证以薄白苔为主;气血两虚证以薄黄苔、薄白苔为主;肝肾阴虚证以薄白苔和薄黄苔为主。舌下络脉存在显著异常者多见。
     四、证与肿瘤标志物的相关研究
     本次调查的大肠癌晚期患者CEA浓度以瘀毒蕴结证最高,并依气血两虚证、肝肾阴虚证、脾肾阳虚证、大肠湿热证依次降低。肝肾阴虚证CA199, CA125, CA153水平高于其它各组(p<0.05),但瘀毒蕴结证、气血两虚证、脾肾阳虚证、大肠湿热证各组间无差异(P>0.05)。大肠癌晚期患者各证型组间AFP无显著差异(P>0.05)。
     结论:
     一、通过横断面流行病学调查,结合临床实践,提示出大肠癌晚期临床常见五大主要证候群为瘀毒蕴结证,大肠湿热证,脾肾阳虚证,气血两虚证,肝肾阴虚证。脏腑本虚是肿瘤发病的根本,瘀毒内阻、湿热郁结是肿瘤发生的基本病理变化,“瘀”、“毒”、“湿”、“热”可能为大肠癌的进展的促使因素。从每一分类的临床症状可知,每个分类所体现的中医证型都不是单一的,而是兼杂有其他中医证型的临床特征,由于肿瘤本身病理的复杂性,随着疾病进展,证候分布及演变均呈现复杂化。
     二、大肠癌晚期患者舌象的研究中,每个类型的舌象均呈现不同的“瘀”的表现,瘀血舌象所占比重最重,尤其在舌下络脉的观察中,舌下络脉存在显著异常者多见。由此推论在大肠癌的的病理机制中“瘀”占有相当大的地位。
     三、大肠癌晚期患者常见肿瘤标志物CEA, CA199, CA125, CA153均呈阳性表达,与临床辨证分型相关,对几项肿瘤标志物的联合检测,可协助肿瘤诊断,指导临床辨证分型,并进一步指导临床用药治疗。
     结语:
     本论文创新点:
     一、首次以大肠癌晚期疾病为切入点,开展其临床症状规律、证型分布研究,从数理统计方面验证了中医“证候”的复杂性,多维性。
     二、运用因子分析方法对大肠癌晚期患者舌象进行分析,探讨大肠癌晚期患者舌象特点,并认为“瘀”、“毒”、“湿”、“热”、“虚”是晚期大肠癌的主要病机;舌下络脉异常者多见,突出了在大肠癌晚期患者的病理机制中“瘀”占相当大地位。
     三、本研究对大肠癌晚期患者常见肿瘤标志物与证型关系进行分析,联合检测肿瘤标志物可指导大肠癌晚期患者的临床辨证分型,并促进证型的客观化研究。
Objective
     By researching the colorectal cancer disease of traditional Chinese medical syndrome of factors related to many factors for popular learn disease survey analysis and study, understand the colorectal cancer disease of TCM syndrome distribution rule and characteristics, and analysis of the tongue and syndrome, the relationships between further discussed colorectal cancer disease syndrome, which for clinical better on syndrome differentiation and treatment of colorectal cancer disease provide theoretical basis.
     Methods
     Study objective:Case Source:January2011to December2011,100cases of colorectal cancer patients hospitalized in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine. Collection of the patient's clinical symptoms, signs, and laboratory parameters. Using transection clinical epidemiology research methods. Meet the diagnostic criteria do not meet the exclusion criteria were included in the study. Case selection criteria in accordance with the the colorectal diagnostic criteria with reference to the Secretary for Home Affairs of the People's Republic of China "New common malignancy in the specification of colorectal cancer diagnostic criteria. The clinical staging TNM staging internationally recognized. TCM standards refer to "Chinese medicine clinical research guidelines, Fifth Edition textbook of clinical medicine diagnostic terminology syndrome part","clinical TCM oncology and Diagnostics of Chinese Medicine (Revised Edition) the dialectical part, finishing Ecchymosis Accumulation card, damp-heat syndrome large intestine, spleen deficiency syndrome, deficiency of both qi and blood, liver and kidney yin deficiency syndrome five main card type. Tongue diagnosis part of the materials refer to the Diagnostics of Chinese Medicine Fifth Edition (Revised Edition) tongue diagnosis part of the contents of. Statistical analysis:After the end of the survey, all survey data are summarized, entered into the computer, the establishment of a database, data management, with SPSS16.0software for statistical analysis. Patients indicators for statistical analysis to compare. Patients tongue, TCM Hou. Statistical methods:Classification using chi-square test, multiple were compared using analysis of variance, this diverse group was used to compare the q-test, TCM clinical symptoms were analyzed using the the samples cluster analysis and exploratory factor analysis method. Statistical analysis on the early steps of colorectal cancer disease syndrome diagnostic indicator, card type, distribution and epidemiological characteristics.
     Results
     1. clinical symptoms
     Surveyed100patients with colorectal cancer clinical symptoms, diarrhea highest frequency of76cases, accounting for (76.0%). Followed by intra-abdominal lumps, a total of70cases (70.0%). Other higher frequency (≥50%) the clinical symptoms of lassitude, poor appetite and indigestion, mucus pus and blood, weight loss, bloating, less gas lazy words, Yaoxisuanruan, scanty dark urine. Tongue performance the scalloped tongue (40.0%), dark red tongue (34.0%), the fat big tongue (33.0%), there is a higher frequency of tongue characteristics; mainly thin white, yellow and greasy tongue coating (29.0%), followed by thin yellow (23.0%); sublingual vein in91patients (91.0%) patients with the sublingual vein density mesh changes in small blood vessels,76cases (76.0%) sublingual vein trunk length greater than3/5,62cases (62.0%) sublingual collaterals full uplift, slightly curved or limitations varicose the sublingual vein color purple59cases, accounting for59.0%. Astringent pulse the clock larger proportion of34cases (34.0%), followed by pulse a few slip in23cases (23.0%).
     2. clinical syndromes
     According to the results of cluster analysis, combined with expert advice, colorectal cancer patients with advanced disease syndrome type more reasonable divided into five categories, namely Ecchymosis Accumulation card, damp-heat syndrome large intestine, spleen deficiency syndrome, deficiency of both qi and blood, liver and kidney yin deficiency. Toxin Accumulation Type, spleen and kidney yang highest frequency, followed by the large intestine damp-heat, liver kidney yin deficiency of both qi and blood. Ecchymosis Accumulation card The main symptoms are:hard intra-abdominal mass, abdominal caking, mucus pus and blood, diarrhea, dark purple lips, dull complexion, dark purple color, skin a mistake, urine short red, weight loss, lassitude, abdominal irritation, tenesmus, sticky mouth, tongue and pulse sublingual veins dense mesh of small blood vessels, dark purple veins astringent, sublingual venae color, sublingual collaterals trunk length greater than3/5, the tongue dark red petechiae tongue, sublingual vein width of2mm to2.6mm, sublingual vein diffuse Varicose. Large intestine damp-heat syndrome symptoms:mucus pus and blood, tenesmus, thirst, scanty dark urine, abdominal pain, limb heaviness, dry mouth and throat, anal burning, insomnia, diarrhea, mouth pain, abdominal distension, poor appetite and indigestion, mouth sticky, irritability, chest tightness, and so on. Tongue and pulse, slippery pulse, yellow greasy moss, sublingual collaterals dense mesh of small blood vessels, the trunk length greater than3/5, red tongue, sublingual vein color bruising, full uplift, slightly curved, sublingual collaterals varicose limitations. Spleen deficiency syndrome symptoms: abdominal pain, chills, cold extremities, lassitude, diarrhea, less gas lazy words, eat less poor appetite, pale and tasteless mouth sublingual collaterals full uplift, slightly curved lip A pale, dizziness, end grain is not, intra-abdominal caking, shortness of breath, weak waist, weight loss, abdominal distension. Sublingual vein dense mesh of small blood vessels, varicose limitations, the sublingual venae color purple, thin white fur, pale tongue, fat tongue, scalloped tongue, sublingual collaterals trunk length greater than3/5, the width of2mm to2.6mm, thin pulse. Deficiency of both qi main symptoms are:dizziness, abdominal distension, waist and knees, poor appetite and indigestion, color dark purple, mucus pus and blood, aversion to cold, a pale lips, tenesmus, diarrhea, spontaneous sweating, shortness of breath, pale complexion, abdominal irritation, hard lumps, intra-abdominal lumps, swollen limbs, tongue and pulse sublingual collateral limitations varicose, the small blood vessels of the dense mesh backbone length is less than3/5, sublingual veins bruising full uplift, slightly curved, the petechiae tongue, dark pale tongue, thin pulse, pulse astringent, sublingual vein width of2mm to2.6mm, sublingual vein Zihei, thin yellow tongue coating, scalloped tongue. The main symptoms of liver kidney yin:insomnia, waist and knees, dry mouth and throat, abdominal pain, abdominal lumps, five upset hot, thirst, weight loss, abdominal distension, scanty dark urine, lassitude, dry stool, dizziness, irritability, less gas lazy words, constipation, tinnitus, palpitations, chest tightness, dull complexion, night sweats, zygomatic red, dark purple lips, mouth pain, anal, a pale lips. Tongue and pulse the sublingual vein trunk length is greater than3/5, pulse string breakdown, a dense mesh of small blood vessels, thin tongue sublingual vein stripping moss, purple-red tongue, red tongue, sublingual collaterals full uplift, slightly curved, width of lingual vein2mm to2.6mm, thin yellow moss. Pathological classification of colorectal cancer is adenocarcinoma, moderately differentiated tubular adenocarcinoma (90.0%), the pathological type no significant difference between the various syndromes.
     3. certificate and his tongue
     The colorectal cancer Tongue, tongue like the following characteristics: In100cases, six cases of the dark tongue in34cases, the pale tongue26cases,5cases of light red tongue, red tongue20cases, purple tongue, purple tongue, two cases, short dark tongue in7cases. Pale tongue, dark red tongue, red tongue proportion of heavy, dark red tongue up. Toxin Accumulation card to dark red tongue, petechiae, ecchymosis tongue main the; large intestine damp-heat syndrome red tongue; spleen deficiency syndrome mainly light red tongue, pale tongue; deficiency of both qi and blood, pale tongue, short dark tongue-based, liver kidney yin dark red tongue, purple-red tongue, red tongue.100cases subjects,29cases of thin white coating, yellow greasy moss in29cases,23cases of thin yellow moss, yellow thick moss in8cases, stripping the moss in7cases,6cases of Bai Yun moss,1case of greasy moss, white thick moss in1cases. Ecchymosis Accumulation certificate to thin yellow moss, yellow greasy moss, yellow thick moss-based; colorectal hot and humid card yellow greasy moss-based; spleen deficiency card to thin white coating; deficiency of both qi and blood to thin yellow coating, thin white moss; liver kidney yin thin white coating and thin yellow coating. The sublingual vein significant abnormalities were more common.
     4. Syndrome Patterns and correlation of tumor markers Patients with advanced colorectal cancer CEA concentration Ecchymosis Accumulation Type is the highest. And blood deficiency of both liver and kidney certificate, spleen deficiency syndrome, large intestine damp-heat syndrome in descending order. Liver kidney yin (CA199, CA125, CA153) level is higher than the other groups (p<0.05), but two of the the Ecchymosis Accumulation card, blood deficiency, spleen deficiency syndrome, large intestine damp-heat syndrome among groups difference (P>0.05). AFP was no significant difference (P>0.05) in patients with advanced colorectal cancer syndrome groups.
     Conclusion
     1. with advanced colorectal cancer five major syndromes group Ecchymosis Accumulation card, damp-heat syndrome large intestine, spleen deficiency syndrome, deficiency of both qi and blood, liver and kidney yin deficiency syndrome. The organs of the virtual fundamental tumor incidence. Ecchymosis resistance, damp heat stagnation is the underlying pathology of the tumor,"stasis","poisonous","wet","hot" may be factors of colorectal cancer progression, due to the complexity of the tumor itself, as the disease progresses, the card syndrome distribution and evolution showed complicated.
     2. study of colorectal Tongue, tongue pictures of the heaviest share of sublingual vein there is a significant abnormalities were more common. Played a very important role in the pathogenesis of colorectal's "stasis". Patients with advanced colorectal cancer tumor markers CEA, CA199, CA125, AFP, CA153joint detection is not only an important basis for the diagnosis of colorectal cancer, and TCM syndrome type.
     Epilogue
     Innovations in this paper:
     1. Advanced colorectal cancer disease as the research object, we carried out the law of clinical symptoms, syndromes of research, from the statistical validation of syndromes complex, multidimensional.
     2. Tongue of advanced colorectal cancer patients for the study, we have carried out a study of the Tongue, Tongue characteristics of colorectal cancer patients with advanced, understanding of the clinical features of colorectal disease Tongue and formation mechanism.
     3. Analysis of advanced colorectal cancer tumor markers and syndromes relationship, we propose the combined detection of tumor markers for colorectal cancer syndrome type reference, and to help syndromes for objective research.
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