諸佳瑜， 徐 望， 陳 闖， 歐 杰， 毛素菲， 莫曉麗， 陸冬玲

(1 廣西中醫(yī)藥大學(xué)， 南寧 530000； 2 湖南省岳陽(yáng)市中醫(yī)院， 湖南 岳陽(yáng) 414000；3 廣西醫(yī)科大學(xué)附屬腫瘤醫(yī)院， 南寧 530000)

隔姜灸聯(lián)合經(jīng)肝動(dòng)脈化療栓塞術(shù)治療肝郁脾虛型原發(fā)性肝癌的效果觀察

諸佳瑜1， 徐 望2， 陳 闖3， 歐 杰3， 毛素菲3， 莫曉麗1， 陸冬玲3

(1 廣西中醫(yī)藥大學(xué)， 南寧 530000； 2 湖南省岳陽(yáng)市中醫(yī)院， 湖南 岳陽(yáng) 414000；3 廣西醫(yī)科大學(xué)附屬腫瘤醫(yī)院， 南寧 530000)

目的 觀察隔姜灸足三里、涌泉穴配合經(jīng)肝動(dòng)脈化療栓塞術(shù)(TACE)治療原發(fā)性肝癌的臨床療效。方法 收集2013年12月-2014年12月于廣西醫(yī)科大學(xué)附屬腫瘤醫(yī)院住院的中醫(yī)證候?qū)俑斡羝⑻撟C的原發(fā)性肝癌初診患者60例，隨機(jī)分為艾灸組和對(duì)照組，每組各30例。兩組患者均行TACE治療，術(shù)后均給予常規(guī)護(hù)肝、護(hù)胃、止痛、止吐等對(duì)癥支持治療。艾灸組在此基礎(chǔ)上，自TACE術(shù)前1 d開始進(jìn)行艾灸治療。施灸穴位取雙側(cè)涌泉穴、雙側(cè)足三里，1次/d，30 min/次，連續(xù)施灸8 d。于術(shù)前1 d和術(shù)后7 d記錄肝癌患者的生活質(zhì)量，對(duì)比兩組患者術(shù)后不良反應(yīng)、中醫(yī)證候評(píng)分和生命質(zhì)量測(cè)定量表EORTC QLQ-C3問(wèn)卷結(jié)果變化。計(jì)量資料組間比較采用t檢驗(yàn)；計(jì)數(shù)資料組間比較采用χ2檢驗(yàn)，等級(jí)資料組間比較采用Mann-WhitneyU檢驗(yàn)。結(jié)果 艾灸組患者術(shù)后出現(xiàn)惡心、嘔吐癥狀等不良反應(yīng)較對(duì)照組少，差異有統(tǒng)計(jì)學(xué)意義(Z=9.692，P=0.046)。艾灸組中醫(yī)證候顯著改善7例，部分改善16例，總有效率為77%；對(duì)照組中醫(yī)證候顯著改善5例，部分改善9例，總有效率為47%，兩組比較差異有統(tǒng)計(jì)學(xué)意義(χ2=7.198，P=0.027)。生活質(zhì)量方面，艾灸組患者疲倦、食欲減退、惡心嘔吐以及總體健康狀況的改善情況均明顯優(yōu)于對(duì)照組(t值分別為2.722、2.530、2.538、3.144，P值分別為0.011、0.017、0.017、0.004)。結(jié)論 雙側(cè)足三里、涌泉穴隔姜灸配合TACE治療原發(fā)性肝癌，可減輕TACE術(shù)后不良反應(yīng)，改善患者中醫(yī)證候及生活質(zhì)量，體現(xiàn)了“局部+全身”的綜合治療模式治療原發(fā)性肝癌的特點(diǎn)和優(yōu)勢(shì)。

肝腫瘤； 隔姜灸； 肝氣郁結(jié)； 脾虛； 治療

經(jīng)肝動(dòng)脈化療栓塞術(shù)(TACE)被公認(rèn)為治療中晚期肝癌的有效方法，但TACE術(shù)后易出現(xiàn)栓塞綜合征、消化道反應(yīng)及肝功能損傷等不良反應(yīng)，嚴(yán)重降低了患者的生活質(zhì)量。研究[1]表明中醫(yī)治療具有提高肝癌患者免疫力、改善體質(zhì)、減少化療的不良反應(yīng)等多方面作用，能夠改善癥狀，控制復(fù)發(fā)轉(zhuǎn)移，延長(zhǎng)生存期。既往有應(yīng)用艾灸治療肝癌的相關(guān)研究[2-4]，但與TACE聯(lián)合治療肝癌的研究尚少。本研究觀察隔姜灸雙側(cè)足三里、涌泉穴對(duì)原發(fā)性肝癌患者TACE術(shù)后不良反應(yīng)、中醫(yī)證候和生存質(zhì)量的影響。

1 資料與方法

1.1 研究對(duì)象 收集2013年12月-2014年12月于廣西醫(yī)科大學(xué)附屬腫瘤醫(yī)院中醫(yī)科、介入治療科住院的中醫(yī)證候?qū)俑斡羝⑻撟C的原發(fā)性肝癌初診患者，隨機(jī)分為艾灸組和對(duì)照組。納入標(biāo)準(zhǔn)：(1)符合原發(fā)性肝癌的診斷標(biāo)準(zhǔn)[5]，包含肝細(xì)胞癌、膽管細(xì)胞癌和混合細(xì)胞癌；(2)由2位副主任以上醫(yī)師進(jìn)行中醫(yī)辨證，符合肝郁脾虛證型，且意見一致者；(3)符合原發(fā)性肝癌TACE治療指征，且同意治療者；(4)同意或者要求隔姜灸治療者；(5)治療期間的臨床資料完整者；(6)體力狀態(tài)評(píng)估評(píng)分<2分，預(yù)計(jì)生存期>3個(gè)月；(7)自愿參加臨床研究并簽署知情同意書。排除標(biāo)準(zhǔn)：(1)繼發(fā)性肝癌及其他惡性腫瘤患者；(2)器質(zhì)性心臟病伴心功能不全或精神障礙性疾病患者；(3)施灸處皮膚潰瘍明顯或施灸后皮膚過(guò)敏者。

1.2 研究方法 兩組患者取平臥位，行常規(guī)消毒，鋪無(wú)菌巾，2%利多卡因10 ml局部麻醉成功后，取右股動(dòng)脈穿刺點(diǎn)，穿刺成功后置動(dòng)脈鞘。將肝導(dǎo)管置入腹腔干、肝動(dòng)脈造影，將微導(dǎo)管超選至動(dòng)脈腫瘤供血分支內(nèi)，予奧沙利鉑85 mg/m2+雷替曲塞3 mg/m2灌注化療，予雷替曲塞2 mg+40%碘化油8 ml混合乳劑栓塞，術(shù)畢，拔出導(dǎo)管，加壓包扎穿刺口。對(duì)照組患者術(shù)后僅給予常規(guī)護(hù)肝、護(hù)胃、止痛、止吐等對(duì)癥支持治療。艾灸組在此基礎(chǔ)上，自TACE術(shù)前1 d開始進(jìn)行艾灸治療。施灸穴位[6]：涌泉穴(雙側(cè))、足三里(雙側(cè))。操作方法：鮮生姜片切成直徑為2～3 cm、厚0.2～0.3 cm的薄片，中間以針刺數(shù)孔，置于患者雙側(cè)足三里、涌泉穴皮膚上，每個(gè)穴位1片；將插有艾條的艾灸盒蓋于貼有生姜片的穴位上，位置適合后扣上松緊帶。詢問(wèn)患者有無(wú)不適癥狀，并適當(dāng)調(diào)節(jié)艾火的位置，以免燙傷患者皮膚，以皮膚紅暈為度。1次/d，30 min/次，連續(xù)施灸8 d。

2 結(jié)果

2.1 一般資料 共納入原發(fā)性肝癌患者60例，其中艾灸組與對(duì)照組各30例。兩組患者在性別、年齡、BCLC分期、Child-Pugh分級(jí)等方面比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P值均>0.05)(表1)，具有可比性。

表1 兩組患者臨床資料

2.2 不良反應(yīng) 艾灸組患者出現(xiàn)惡心、嘔吐的不良反應(yīng)較對(duì)照組少，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；在發(fā)熱、疼痛、周圍神經(jīng)癥狀、肝腎功能異常等方面，兩組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P值均>0.05)(表2)。

2.3 中醫(yī)證候評(píng)分 觀察兩組患者治療后脅痛、腹脹、乏力、腹瀉、納呆、消瘦等中醫(yī)證候評(píng)分情況。艾灸組中醫(yī)證候顯著改善7例，部分改善16例，無(wú)改善7例，總有效率77%；對(duì)照組中醫(yī)證候顯著改善5例，部分改善9例，無(wú)改善16例，總有效率47%。前者的中醫(yī)證候改善情況較對(duì)照組明顯，差異有統(tǒng)計(jì)學(xué)意義(χ2=7.198，P=0.027)。

2.4 生活質(zhì)量測(cè)定 艾灸組患者在疲倦、食欲減退、惡心嘔吐以及總體健康狀況方面改善明顯優(yōu)于對(duì)照組，差異均有統(tǒng)計(jì)學(xué)意義(P值均<0.05)(表3)。

表2 兩組患者不良反應(yīng)比較(例)

注：0～Ⅳ代表不良反應(yīng)程度，數(shù)值越大，不良反應(yīng)程度越大

表3 兩組患者生活質(zhì)量測(cè)定結(jié)果比較±s，分)

3 討論

腫瘤是一種全身性疾病，針對(duì)局部的治療干預(yù)無(wú)法徹底解決其轉(zhuǎn)移、復(fù)發(fā)等問(wèn)題，因此“局部+全身”的綜合治療模式已成為目前治療肝癌的主要趨勢(shì)[8]。由于化療藥物的毒性作用，TACE術(shù)后患者常出現(xiàn)惡心嘔吐、食欲不振、疲倦等不良反應(yīng)，屬中醫(yī)的肝郁脾虛證候。李泉旺等[9]觀察原發(fā)性肝癌介入治療前后證型演變，結(jié)果顯示TACE術(shù)后患者氣滯、脾虛、血瘀證候加重。艾灸作為中醫(yī)外治法的一部分，特別適用于一些慢性、虛損性疾病的防治?，F(xiàn)代醫(yī)學(xué)研究[10]表明，艾灸對(duì)腧穴的溫?zé)岽碳た梢约ぐl(fā)經(jīng)絡(luò)之氣，調(diào)節(jié)各器官功能，增強(qiáng)機(jī)體免疫力，減輕疾病對(duì)機(jī)體的損害，且操作簡(jiǎn)便，成本低廉，患者依從性較高[11]。因此本研究采用隔姜灸療法，取足三里穴、涌泉穴調(diào)理脾胃、補(bǔ)益正氣之作用，結(jié)果顯示艾灸組患者惡心、嘔吐癥狀出現(xiàn)次數(shù)明顯少于對(duì)照組，表明隔姜灸足三里、涌泉穴可有效減輕TACE術(shù)后的消化道不良反應(yīng)。現(xiàn)代研究[12-13]發(fā)現(xiàn)艾葉燃燒時(shí)產(chǎn)生的熱能主要是易被人體吸收的近紅外線，可促進(jìn)機(jī)體細(xì)胞代謝，提高機(jī)體的免疫力，同時(shí)艾灸燃燒時(shí)產(chǎn)生的艾煙也可提高細(xì)胞免疫功能。艾灸對(duì)胃腸道的作用是通過(guò)神經(jīng)傳導(dǎo)機(jī)制產(chǎn)生，足三里的傳入神經(jīng)在腰骶段有交匯重疊，研究[14]提示其機(jī)制與膽堿能神經(jīng)和M型受體有關(guān)，通過(guò)迷走神經(jīng)發(fā)揮作用，恢復(fù)胃動(dòng)力和胃慢波損傷，增加正常胃慢波比率，以消除上腹脹滿噯氣、惡心、納差、餐后不適等不良反應(yīng)[15]。

帶瘤生存是多數(shù)中晚期惡性腫瘤患者的治療目的，總生存期、生存率等生存獲益指標(biāo)是評(píng)價(jià)腫瘤治療效果的金標(biāo)準(zhǔn)。目前，療效評(píng)價(jià)原則已從單純追求生存率逐步轉(zhuǎn)變?yōu)樯媛逝c生活質(zhì)量并重，故采用“實(shí)體瘤療效評(píng)價(jià)標(biāo)準(zhǔn)”評(píng)價(jià)中醫(yī)治療腫瘤的療效稍顯片面[16]，因此從中醫(yī)治療腫瘤的優(yōu)勢(shì)與特色出發(fā)，將中醫(yī)證候評(píng)分及生活質(zhì)量測(cè)定等觀察指標(biāo)納入中醫(yī)腫瘤療效評(píng)價(jià)體系十分必要，同時(shí)也能體現(xiàn)當(dāng)今國(guó)際腫瘤界提倡“將腫瘤作為一種慢性病治療”的宗旨[17]。本研究結(jié)果顯示艾灸組中醫(yī)證候總有效率為77%，明顯優(yōu)于對(duì)照組，表明艾灸足三里、涌泉穴對(duì)改善TACE術(shù)后中醫(yī)證候和總體健康狀況方面有較好優(yōu)勢(shì)。但本研究艾灸治療時(shí)間較短且樣本量偏少，今后應(yīng)擴(kuò)大樣本量及延長(zhǎng)患者隨訪時(shí)間，以更好地反映艾灸聯(lián)合TACE治療肝癌的效果，為艾灸輔助治療肝癌提供臨床依據(jù)。

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引證本文：ZHU JY, XU W, CHEN C, et al. Clinical effect of ginger-partitioned moxibustion combined with transarterial chemoembolization in treatment of primary liver cancer with stagnation of liver qi and spleen deficiency[J]. J Clin Hepatol, 2017, 33(1): 87-90. (in Chinese) 諸佳瑜， 徐望， 陳闖， 等. 隔姜灸聯(lián)合經(jīng)肝動(dòng)脈化療栓塞術(shù)治療肝郁脾虛型原發(fā)性肝癌的效果觀察[J]. 臨床肝膽病雜志, 2017, 33(1): 87-90.

(本文編輯：葛 俊)

Clinical effect of ginger-partitioned moxibustion combined with transarterial chemoembolization in treatment of primary liver cancer with stagnation of liver qi and spleen deficiency

ZHUJiayu,XUWang,CHENChuang,etal.

(GuangxiUniversityofChineseMedicine,Nanning530000,China)

Objective To investigate the clinical effect of ginger-partitioned moxibustion at Zusanli and Yongquan points combined with transarterial chemoembolization (TACE) in the treatment of primary liver cancer. Methods A total of 60 patients initially diagnosed with primary liver cancer with stagnation of liver qi and spleen deficiency who were hospitalized in The Affiliated Tumor Hospital of Guangxi Medical University from December 2013 to December 2014 were enrolled and randomly divided into moxibustion group and control group, with 30 patients in each group. The patients in both groups were given TACE and symptomatic/supportive treatment after TACE, including conventional liver-protecting, stomach-protecting, pain-relieving, and antiemetic treatment. The patients in the moxibustion group were given moxibustion since day 1 before TACE. Moxibustion was performed at bilateral Yongquan and Zusanli points once a day (30 minutes each time) for 8 consecutive days. The patients′ quality of life was recorded at 1 day before and 7 days after surgery, and the postoperative adverse events, traditional Chinese medicine (TCM) syndrome score, and EORTC QLQ-C30 results were compared between the two groups. Thet-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and the Mann-WhitneyUtest was used for comparison of ranked data between groups. Results The moxibustion group had a significantly lower proportion of patients who experienced nausea and vomiting after surgery than the control group (Z=9.692,P=0.046). Among the patients in the moxibustion group, 7 achieved significant improvements in TCM syndrome and 16 achieved partial improvements in TCM syndrome, resulting in an overall response rate of 77%; among the patients in the control group, 5 achieved significant improvements and 9 achieved partial improvements, resulting in an overall response rate of 47%; there was a significant difference in overall response rate between the two groups (χ2=7.198,P=0.027). As for the quality of life, the moxibustion group had significantly better improvements in fatigue, anorexia, nausea/vomiting, and general health compared with the control group (t=2.722, 2.530, 2.538, and3.144,P=0.011, 0.017, 0.017, and 0.004). Conclusion Ginger-partitioned moxibustion at bilateral Zusanli and Yongquan points combined with TACE for the treatment of primary liver cancer can alleviate the adverse effects after TACE and improve patients′ TCM syndrome and quality of life. This combined therapy reflects the features and advantages of “l(fā)ocal and systemic” combined-modality therapy for primary liver cancer.

liver neoplasms； ginger-partitioned moxibustion； liver-qi depression； spleen deficiency； therapy

10.3969/j.issn.1001-5256.2017.01.018

2016-08-26；

2016-10-12。

2015年廣西科學(xué)研究與技術(shù)開發(fā)計(jì)劃項(xiàng)目(桂科攻1598012-54)

諸佳瑜(1991-)，女，主要從事腫瘤的中西醫(yī)結(jié)合防治研究。

陳闖，電子信箱：ch1ch2@163.com。

R735.7； S853.618

A

1001-5256(2017)01-0087-04