【作者】 郝淑芳；

【导师】 常钢；

【作者基本信息】 广州中医药大学 ， 中西医结合临床， 2009， 博士

【摘要】 背景大部分恶性梗阻性黄疸在确诊时已失去根治性手术机会,手术切除率低。胆道支架置入术是目前首选的姑息治疗恶性梗阻性黄疸方法。但支架置入术感染率高、术后再狭窄大大影响临床疗效。肿瘤生长是造成支架堵塞、黄疸复发的主要原因。碘-125粒子是一种新型放射源,具有低剂量率、可持续照射等特点,将碘-125粒子应用于胆道腔内照射治疗,控制局部肿瘤生长,有望解决胆道支架置入后再狭窄问题。联合中医药辨证施治有望提高患者免疫力,减少感染的发生,从而提高患者对介入治疗的耐受性。目的观察恶性梗阻性黄疸患者介入治疗前后中医证候的变化,为恶性梗阻性黄疸围介入期的中医辨证施治提供参考;评价艾迪注射液治疗恶性黄疸气虚毒瘀证的临床疗效,验证其提高患者免疫功能、减少感染发生率的作用;探讨自制留置导管进行碘-125粒子胆道腔内准确置入的可行性;评价碘-125粒子腔内照射防治胆道支架置入术后再狭窄的临床疗效;寻找一种中西医结合治疗恶性梗阻性黄疸的最佳方案,以发现一种解决胆道支架置入术后再狭窄问题的有效手段,从而提高临床疗效。方法采用前瞻性非随机对照试验,观察艾迪注射液及碘-125粒子胆道腔内放疗治疗失去根治性手术机会的恶性梗阻性黄疸的临床疗效。临床观察2005年10月~2008年4月恶性梗阻性黄疸住院病人38例,治疗组(支架+粒子组)19例,对照组(单纯支架组)19例。治疗组内应用艾迪共8例,对照组内应用艾迪共11例。观察各组介入治疗前后中医证候积分、肝功能各项指标、KPS评分、CEA、感染发生率、感染持续时间、生存率、中位生存时间及无黄疸生存时间等指标。结果治疗组与对照组在年龄、性别构成上的差异均无统计学意义(P＞0.05)。经Fisher’s确切概率检验,肿瘤类型在两组构成差异有统计学意义(P＜0.05)。38例患者介入治疗前黄疸、腹痛、口干口苦、心烦易怒等标实证候积分显著升高,同时纳呆食少、少气懒言、乏力肢软等本虚证积分也升高;经配对t检验,介入术后1周患者上述标实证积分与术前比较有明显降低,差异有统计学意义(P＜0.05)。少气懒言、乏力肢软、腹胀等本虚证积分与术前比较有所降低,差异有统计学意义(P＜0.05);介入术后一个月各项证候积分除发热与纳呆食少外较术前均有明显降低,差异有统计学意义(P＜0.05)。全部病例在介入治疗术后一周、一月、三月内大部分肝功能指标呈现逐渐降低的趋势。其中术后一周、一月、三月ALT、AST、TBIL、DBIL、GGT、TBA均较术前明显降低,经配对t检验,差异均有统计学意义(P＜0.05)。全部病例术后一周、一月KPS均较术前明显升高,经配对t检验分析,差异有统计学意义(P＜0.05)。全部病例中应用艾迪组发生感染例数比不用艾迪组少,感染发生率稍低,经χ~2检验,差异无统计学意义(χ~2=0.792,P=0.660)。全部病例中应用艾迪组发生感染天数比不用艾迪组短,经t检验,差异无统计学意义(P＞0.05)。治疗组术后一周、一月、三月、六月肝功能指标ALT、AST、TBIL、DBIL、GGT、TBA均较术前降低,其中术后一周较术前明显降低,经t检验,差异有统计学意义(P＜0.05)。治疗组术后一周、一月、六月较术前明显降低,经t检验,差异有统计学意义(P＜0.05)。对照组术后一周、一月TBIL、DBIL较术前明显降低,经t检验,差异有统计学意义(P＜0.05)。但术后六月ALT、AST、TBIL、DBIL、ALP较术前升高。提示对照组术后六月出现黄疸复发。经t检验,治疗组术后一周、一月KPS较术前明显升高,差异有统计学意义(P＜0.05)。对照组术后一周KPS较术前明显升高,差异有统计学意义(P＜0.05)。两组介入治疗术后六月肝功能各项指标比较,治疗组AST、TBIL、DBIL治疗组明显低于对照组,经t检验,差异有统计学意义(P＜0.05)。介入治疗术后六月治疗组CEA明显低于对照组,经t检验,差异有统计学意义(t=-242.88,P=0.000)。治疗组术后一周、术后一月KPS均比对照组高,经t检验,差异无统计学意义(P＞0.05)。治疗组中位生存时间为456天,对照组中位生存时间为330天,治疗组中位生存时间比对照组长,经检验,差异有统计学意义(P＜0.05)。治疗组术后平均无黄疸生存时间为20.33月,对照组术后平均无黄疸生存时间为13月,治疗组术后无黄疸生存时间比对照组长,经秩和检验,差异有统计学意义(Z=-2.17,P=0.030)。治疗组术后ALT、AST均较术前降低,治疗组术后WBC、BUN、Crea与术前相比。经t检验分析,差异无统计学意义(P＞0.05)。结论介入治疗对恶性梗阻性黄疸中医证候的传变有明显的影响。恶性梗阻性黄疸介入治疗术前本虚标实证候兼具,而以标实证候为主。介入治疗术后本虚证的矛盾相对更加突出。艾迪注射液具有降低恶性梗阻性黄疸感染发生率的作用。经皮肝穿刺胆道引流联合胆道支架置入治疗可以快速解除梗阻,恢复胆汁生理性引流,明显改善患者的肝功能。经皮肝穿刺胆道引流联合胆道支架置入治疗对恶性梗阻性黄疸近期疗效确切。应用自制留置导管进行碘-125粒子胆道腔内准确置入安全可行,碘-125粒子胆道腔内放疗可以部分控制肿瘤组织的生长,延长支架开通时间,改善肝功能,从而延长患者的生存时间。艾迪注射液联合碘-125粒子胆道腔内放疗治疗恶性梗阻性黄疸是一种较好的方案,可以提高临床疗效,延长患者生存期、改善生存质量。更多还原

【Abstract】 BackgroundMost malignant obstructive jaundice are unresectable when diagnosed.The surgery ratio is low.Biliary stent implantation has already become one of the alleviative treatment of the malignant obstructive jaundice,which will effect the therapeutic efficacy,because the stent will become restenosis in some patients after the 3-6months in the clinical practice observation.The high infect rate and restenosis has seriously affected the clinical effect.There has been many tries to resolve the Stent’ s restenosis.However to this day,no effective method has been discovered.The tumor’ s growth is the major reason to the restenosis.Positive treatments to the primary tumor are required.It’ s crucial to raise the forward effect.I-125 seeds which were made in China recently has the characteristic of low dose rate and persistent irradiation, which can redeem the insufficiency of the irradiation and be the permanent radiation source.It is hoped to decrease the restenosis of the stent by applying the I-125 seeds in the bile duct.The unite use of TCM can raise the patient’ s immunity and reduce the infect rate,and can raise the patient’ s toleration to intervention.PurposeTo observe the TCM zhenghou’ s change in the front and the back of the intervention and instruct the TCM diagnosis and treatment.To evaluate the effect of the aidi injection in treatment of the malignant jaundice with deficiency of vital energy,poison and blood stasis syndrom.To evaluate the effect of the aidi injection’ s in raising the patient’ s immunity and reduce the infect rate.To evaluate the feasibility of the applying the I-125 seeds in the bile duct with home-made catheter.To evaluate the effect of the I-125 seeds in the bile duct to prevent and cure the Stent’ s restenosis.To find the best Chinese and Western Medicine solution to treat the malignant obstructive jaundice.To find an effective solution to resolve the Stent’ s restenosis and raise the effect,extend the patient’ s lifetime,improve the patient’ s Quality of Life.MethodWe use control experiment,Prospective Trial.There are thirty eight malignant obstructive jaundice patients in hospital 10th,2005-4th,2008.We put the 19 cases into the treatment group(biliary stent implantation + intraluminal brachytherapy by I-125 seeds) and another 19 cases into the antitheses group(biliary stent implantation).8 cases in the treatment group and 11 cases in the antitheses group use aidi injection.And to valuate the TCM zhenghou’ s change,liver function,KPS score,CEA,the infect rate,the infect duration,survival rate and median survival time in the two group in the front and the back of the intervention.ResultAll the patient’ s jaundice,abdominal pain,feel thirsty and bitter,be disturbed and fretful Score are soar before the intervention.And the above-mentioned Biaoshi syndrome reduce one week after the intervention.The differents have statistics significance(P＜0.05).The Benxu syndrome such as short of breath,don’ t want talk,out of strength,abdominal distension reduce after the intervention.The differents have statistics significance(P＜0.05).All the syndrome except fever and loss of appetite reduce than before the intervention.The differents have statistics significance(P＜0.05).The aidi injection group has a lower infection and shorter infect duration than the other group.The differents haven’ t statistics significance(P＞0.05).All the patient’ s liver function change smaller one week,one month,three month after the intervention than before the intervention.ALT、AST、TBIL、DBIL、GGT、TBA are smaller one week,one month,three month after the intervention than before the intervention.The differents have statistics significance(P＜0.05).KPS increase one week,one month after the intervention.The differents have statistics significance(P＜0.05).The patient’ s liver function such as ALT、AST、TBIL、DBIL、GGT、TBA change smaller in the treatment group one week,one month,three month,six month after the intervention than before the intervention,one week after the intervention change smaller obviously.TBIL、DBIL in the treatment group are smaller one week,one month,three month,six month after the intervention than before the intervention.There are obviously smaller one week,one month,six month after the intervention than before the intervention.The differents have statistics significance(P＜0.05).The liver function change smaller in the antitheses group one week,one month,three month after the intervention than before the intervention.TBIL、DBIL in the antitheses group are smaller one week,one month after the intervention than before the intervention.The differents have statistics significance(P＜0.05).But ALT、AST、TBIL、DBIL、ALP increase six month after the intervention than before the intervention.It remind that the jaundice in the antitheses group recur six month after the intervention.ALT、AST、TBIL、DBIL、GGT、TBA、ALP in the treatment group are smaller than that of the antitheses group six month after the intervention.AST、TBIL、DBIL in the treatment group are seriously smaller than that of the antitheses group. The differents haven’ t statistics significance(P＞0.05).KPS increace one week,one month after the intervention than before the intervention in the two groups.KPS in the treatment group increace seriously one week,one month after the intervention than before the intervention.The differents have statistics significance(P＜0.05).KPS in the antitheses group increace seriously one week after the intervention than before the intervention.The differents have statistics significance(P＜0.05).KPS in the treatment group is more than that of the antitheses group one week,one month after the intervention.The differents have statistics significance(P＜0.05).CEA in the treatment group is seriously smaller than that of the antitheses group six month after the intervention.The differents have statistics significance(P＜0.05).The counts without jaundice in the treatment group are more than that of the antitheses group when the patient die or the last correspondence.The differents have statistics significance(P＜0.05).The median survival time of the treatment group is 456 days.The median survival time of the antitheses group is 330 days.The median survival time of the treatment group is longer than that of the antitheses group.The differents have statistics significance(P＜0.05). The median survival time of the pancreatic cancer IS the longest in the treatment group,it’ s 690 days.And the shortest is the carcinoma of gallbladder,.it’ s 60 days.The differents in different carcinoma type haven’ t statistics significance(P＞0.05).The median survival time of the carcinoma of bile duct IS the longest in the antitheses group,it’ s 330 days.And the shortest is the pancreatic cancer,.it’ s 165 days.The differents in different carcinoma type haven’ t statistics significance in the antitheses group(P＞0.05).ALT、AST in the treatment group change smaller after the intervention than before the intervention.WBC、BUN、Crea in the treatment group after the intervention haven’ t differents than that before the intervention.The differents in different carcinoma type haven’ t statistics significance(P＞0.05).ConclusionThe Intervention has seriously effect to the TCM zhenghou’ s in the malignant obstructive jaundice.Before the Intervention there are Benxu and Biaoshi syndromes,and the Biaoshi syndromes are major.After the Intervention Benxu syndromes are noticeable.Aidi injection can reduce the infect rate of the malignant obstructive jaundice.PTCD combined with Billary stent can get rid of the obstruction,recover the physiologic drainage of the bile, improve the liver function.PTCD combined with Billary stent have precise effection in the treatment of the malignant obstructive jaundice.It’ s feasible to apply the I-125 seeds in the bile duct with home-made catheter. I-125 seeds in the bile duct can inhibit the grouth of the tumor tissue,extend the time of the stent keep smooth,,improve the liver function,extend the survival time of the patients.更多还原