中國冷凍消融治療原發(fā)性肝癌的最新進(jìn)展

2009年世界腫瘤介入學(xué)術(shù)大會匯編CT guided radioactive 1筋I(lǐng) seed implantation compared with firstlinechemotherapy in treating localized advanced pulmonaw carcinoma：acontrol studyzHANG Fu-junZHANG Liang WU Peihong HUANG Jinhua FAN Wei-jun GU Yang-kui LI Chuanxing LI Kui Lu Ming-jianDepartment of Imaging and Interventional Radiology Cancer Center Sun YatSen University Guangzhou 5 10060 ChinaAbstractObjective：To investigate the clinical value ofCT guided radioactive seed 1251 implantation(C3RISI)in the treatmentof localized advanced pulmonary carcinomaMethods：Thirtytwo patients(Group A)with localized advanced pulmonary carcinoma，received radioactive seed1”I implantation after failure in first line chemotherapyThere were 1 5 males，and 1 7 females，ageing from 3 1 to 73 yearsold520 on the averageThere were 48 lesions in the 32 patients altogether and all the lesions had a clear border with theadiacent normal tissueThe diameter of tumors was 4575cmthe average was 55cmAll the cases had been confirmed asmalignant by pathology(percutaneous aspiration biopsy)I seeds of 2加33x10 7megabecquerel(MBq)were implantedinto these lesionsThe total number of the seeds implanted in each】esion was 1 01 00The dosage of the region aroundthe tumor was 100150GyAccording to Treatment Planning System(TPS)，we implant the 125I seeds into the tumorsunder CT guidanceW-e picked 30 patients(Group B)to be treated by first line chemotherapy in our hospital randomly asthe control groupResults：The results of CT followup after two months proved that the local control rate of the group treated with125I seeds implantation was 781one year survival rate Was 650。median survival time was 15 monthsSmall amountof effusion was observed in these patients during operationPneumothorax happened in 4 cases with one of the lungscompressed less than 30 percent and got improved healthy after conservative treatmentOne week after the procedure，bloody sputum occured in l 5 casesNo myelosuppression and other serious complications occurred in these patientsThelocal control rate of the control group was 433、one year survival rate was 480，median survival time was 1l months，the incidence rate of myelosuppression is 463There was a significant difference between the two groupsConclusion：CTGRISI procedure iS safe and welltolerated in treating localized advanced pulmonary carcinoma inChinese patients with few complications；it Can improve the living quality obviously and has good shortterm effects【Key wordsIodine radioisotopes；interventional；brachytherapy；localized advanced stage pulmonary carcinoma；evaluation studies中國冷凍消融治療原發(fā)性肝癌的最新進(jìn)展張積仁史德剛南方醫(yī)科大學(xué)珠江醫(yī)院腫瘤中心本講座論述了中國冷凍消融治療肝癌的最新進(jìn)展，包括6個部分：1在外國友人的幫助下。氬氦冷凍消融技術(shù)被引進(jìn)中國。氬氦冷凍消融技術(shù)是20余項美國航天專利高新技術(shù)的結(jié)晶，1998年FDA批準(zhǔn)使用。19992002年期間，美國有200家醫(yī)院安裝了這種設(shè)備，已經(jīng)取代液氮和其它冷凍外科治療設(shè)備。1999年，第1Nendocare冷凍外科系統(tǒng)在第一軍醫(yī)大學(xué)珠江醫(yī)院使用，國際生物治療學(xué)會主席PKLehtinen和副主席RHanka來到中國為珠江醫(yī)院氬氦冷凍治療中心剪彩。1999年，I掃Peter J Litrup，張積仁和汪森明三位教授在中國珠江醫(yī)院使用Endocare冷凍外科系統(tǒng)完成了第1例冷凍外科手術(shù)。Endocare冷凍外科系統(tǒng)在中國被命名為氬氦冷凍消融(氬氦刀)。1999年，CT引導(dǎo)下經(jīng)皮冷凍消融治療的第l例肝癌患者是TACE術(shù)后在珠江醫(yī)院完成。代表中國氬氦冷凍外科協(xié)作組，我們將非常感謝以下外國友人的幫助和指導(dǎo)中國發(fā)展冷凍治療，這些教授分別是Peter JLitrrup，Suzy Chosy。Daniel Rukstalis，Andre，DPeterson，Gregory Groves，Daniel RlIkstaUs，Go Wakadayash，Winoruanabe and Dan silver，等等。Endocare冷凍外科手術(shù)系統(tǒng)在中國醫(yī)學(xué)科學(xué)院士的指導(dǎo)下已經(jīng)應(yīng)用于腫瘤中心，他們分1102009年世界腫瘤介入學(xué)術(shù)大會匯編別是吳孟超，郝希山，湯釗猷，吳咸中。從1999-2007年，Endocare冷凍外科手術(shù)系統(tǒng)已經(jīng)在中國的70家醫(yī)院中使用。2影像引導(dǎo)下經(jīng)皮冷凍消融的程序在DSA，CT，MR，腹腔鏡，超聲波引導(dǎo)下，冷凍消融有助于治療實體瘤，例如肺癌，肝癌，膠質(zhì)瘤，軟組織腫瘤，乳腺癌，卵巢癌，骨腫瘤，胰腺癌，前列腺癌，腎癌，皮膚腫瘤，肛門直腸癌，口腔癌，宮頸上皮內(nèi)瘤變，等等。使用CT，MR，PET和DSA影像學(xué)觀察了靶向冷凍消融的組織，中國的幾家醫(yī)院報道了臨床結(jié)果。腫瘤標(biāo)記物例如CEA，AFP，PSA，CAl9-9在不同種類的腫瘤冷凍消融治療前后也作了分析。3靶向冷凍消融的基礎(chǔ)研究對于實體瘤冷凍外科有效的治療體現(xiàn)在：(1)動物腫瘤模型的分析，(2)冷凍外科術(shù)后病人體內(nèi)腫瘤組織的檢查；(3)使用免疫學(xué)和分子生物學(xué)方法的研究。最經(jīng)常使用的冷凍消融系統(tǒng)是美國生產(chǎn)的Endocare冷凍治療系統(tǒng)，最近，其他的冷凍外科系統(tǒng)也在中國使用，例如超過10家醫(yī)院使用以色列生產(chǎn)的Galil Medical System。另外，清華大學(xué)也生產(chǎn)一種液氮冷凍消融系統(tǒng)，另一種氮氣冷凍消融系統(tǒng)在上海交通大學(xué)生產(chǎn)，這兩種設(shè)備有望在20082009年的醫(yī)療市場上見到。腫瘤細(xì)胞系冷凍治療前后的變化由幾家醫(yī)院報道。冷凍治療對于正常組織的效果也在動物模型和腫瘤病人進(jìn)行了觀察，例如對于動脈和靜脈，膽管，胰腺和支氣管的效果也進(jìn)行了研究。冷凍消融術(shù)后體內(nèi)靶向治療的腫瘤組織變化進(jìn)行了檢查并得到隨訪，切除的組織標(biāo)本也在體外進(jìn)行了分析。冷凍消融治療的影響因素，例如冷凍消融時間，溫度，血液，氬氣和氦氣的壓力情況，穿刺針的直徑，以及靶向治療的病灶邊緣也被中國醫(yī)生進(jìn)行了研究。治療的有效性在臨床腫瘤學(xué)領(lǐng)域得到驗證，其標(biāo)準(zhǔn)程序也被每一個醫(yī)生熟悉。并且，臨床腫瘤學(xué)的DCs，TLs，NK，LAK，以及細(xì)胞因子方面的冷凍免疫學(xué)研究計劃也進(jìn)行了探討，超過10家醫(yī)院參加了這個項目。4靶向冷凍消融臨床研究除了外科切除和介入治療程序之外，微創(chuàng)外科治療肝癌意義重大。聯(lián)合化療和冷凍治療非小細(xì)胞肺癌；聯(lián)合冷凍消融和放療治療250例非小細(xì)胞肺癌由宋華志報道。他們的結(jié)果顯示聯(lián)合冷凍治療的效果可以延長1年和2年的生存率。聯(lián)合TACE和冷凍治療382例肝癌病人由宋華志報道，分別顯示TACE的有效率328，TACE和冷凍的有效率583。在使用冷凍治療腫瘤的過程中，中國氬氦冷凍外科協(xié)作組總結(jié)了幾種腫瘤治療技術(shù)的選擇要求，包括許多方面，例如適應(yīng)癥，效果，毒性，并發(fā)癥，對于其他治療方法的影響，減輕疼痛，生活質(zhì)量，減少心理負(fù)擔(dān)，經(jīng)濟(jì)花費(社會家庭工作單位)。中國氬氦冷凍外科協(xié)作組呼吁生產(chǎn)廠家重視消融技術(shù)的臨床問題，例如：靶區(qū)消融范圍，立體形狀，臨床指南；靶區(qū)物理及生物學(xué)影響因素；微創(chuàng)消融治療技術(shù)靶區(qū)的適型設(shè)計，靶向定位，靶向引導(dǎo)與導(dǎo)航；消融靶區(qū)的適時監(jiān)測與靶區(qū)控制，靶區(qū)消融后近期與遠(yuǎn)期的評價標(biāo)準(zhǔn)；亞臨床及殘余病灶的治療；綜合治療的選擇。并且，中國氬氦冷凍外科協(xié)作組也強(qiáng)調(diào)了消融治療在腫瘤治療現(xiàn)代模式中的地位，他們編輯了3本冷凍治療書籍，涉及到冷凍靶向消融治療，腫瘤冷凍外科治療和生物醫(yī)學(xué)工程學(xué)的冷凍機(jī)制方面。自從1999年開始，中國生物醫(yī)學(xué)工程學(xué)會腫瘤靶向治療技術(shù)分會召開了靶向消融和微創(chuàng)治療5次國際會議和4次國家級會議。5中國氬氦冷凍外科協(xié)作組治療的腫瘸患者統(tǒng)計數(shù)目2007年11月，第14屆世界冷凍治療大會統(tǒng)計了中國12家醫(yī)院使用美國Endocare冷凍消融系統(tǒng)治療的腫瘤病人，數(shù)目達(dá)到ll，000例，其中超過500例的醫(yī)院分別超過10家，部分醫(yī)院病例數(shù)達(dá)到4000例。冷凍治療了超過30種疾病，與世界其他國家比較，中國治療肝癌和肺癌的病例數(shù)最多。6中國使用冷凍外科系統(tǒng)治療肝癌文獻(xiàn)復(fù)習(xí)2009年4月20日，我們使用中文關(guān)鍵詞“肝癌and氬氦”檢索了1999-2008年期間中國知識基礎(chǔ)設(shè)施工程數(shù)據(jù)庫(ChinaNational Knowledge Infrastructure，CNKI，CJFD)，并且，使用檢索詞”cryoablation and liver cancer”檢索了收錄在PubMed(MEDLINE)數(shù)據(jù)庫中的中國作者文獻(xiàn)。1999-2008年期間共有119篇中國冷凍治療肝癌的文獻(xiàn)，其中118篇文獻(xiàn)大體分為14類別，分別是：(1)肝癌的氬氦刀冷凍治療36篇；(2)超聲引導(dǎo)氬氦刀冷凍消融治療肝癌14篇l(3)CT引導(dǎo)氬氦刀冷凍消融治療肝癌2篇；(4J肝動脈栓塞化療聯(lián)合氬氦刀冷凍消融治療12篇。(5)原發(fā)性肝癌多種微創(chuàng)療法的對比研究及臨床應(yīng)用9篇t(6J其他介入方法聯(lián)合氬氦刀或手術(shù)聯(lián)合氬氦刀治療肝癌2篇，(7)肝癌氬氦刀冷凍術(shù)中靜脈麻醉、監(jiān)測、手術(shù)技巧3篇；(8)中西醫(yī)結(jié)合氬氦刀消融治療肝癌5篇；(9)經(jīng)皮肝穿刺氬氦刀冷凍術(shù)治療肝癌的副反應(yīng)和并發(fā)癥9篇，護(hù)理13篇。術(shù)后影像學(xué)方法評價療效5篇；肝癌冷凍消融治療合理選擇與評價3篇，對于免疫學(xué)、肝功能等方面影響的實驗室研究4篇；其他方面試驗研究l篇。冷凍消融治療后腫瘤患者l，2，3，4，5年生存率的統(tǒng)計也作了分析，分別是348-985，25-636，42-583，但是沒有4，5年的生存率。冷凍消融為基礎(chǔ)的聯(lián)合治療效果比單純冷凍或TACE要好，聯(lián)合冷凍治療后l，2年的生存率分別是83和618-917。另外，與肝癌冷凍治療有關(guān)的513篇文獻(xiàn)收錄在Medline中，其中40篇由中國作者寫作。2008年Xu KC，Niu LZ，Hu YZ等總結(jié)了326例肝癌病人使用Endocare經(jīng)皮氬氦冷凍消融治療后1，2，3，4，5年的生存率，分別是78，62，41，3400，1112009年世界腫瘤介入學(xué)術(shù)大會匯編232006年，Chen SG，Zhang SM，Zhao HT等比較了73例以冷凍手術(shù)為基礎(chǔ)的聯(lián)合治療(液氮，LCS-2000，英國生產(chǎn))與239例以TACE為基礎(chǔ)的聯(lián)合治療的生存率，l，3，5年生存率分別是644，384，274l和751，290，1002002年，Rui JA，Wang SBChela SG等報道了191例外科切除和70例冷凍外科(液氮)的治療結(jié)果，l，3，5年生存率分別是758，456，304和632，37O，但是沒有5年的冷凍外科結(jié)果。40篇文獻(xiàn)中，16篇是由Zhou XD，Tang ZY，YuY等作者撰寫，是關(guān)于液氮冷凍治療肝癌病人的結(jié)果。2002年。他們報道了84例肝癌病人治療后l，3，5年的生存率分別是987，839，64O總結(jié)：11)超聲波或CT引導(dǎo)下的經(jīng)皮冷凍消融治療肝癌是一種安全有效的微創(chuàng)治療技術(shù)。(2)聯(lián)合TACE和冷凍消融治療對于進(jìn)展期原發(fā)性肝癌的療效好于單一技術(shù)的療效。(3)這種技術(shù)可以提高生存率和生活質(zhì)量，對于失去手術(shù)切除治療機(jī)會的肝癌患者，開創(chuàng)了一個新的治療方式。(4)在冷凍消融治療肝癌的微創(chuàng)介入治療領(lǐng)域，中國對于世界作出了重大貢獻(xiàn)?！娟P(guān)鍵詞】肝癌。氬一氦液氮，冷凍消融，冷凍外科The latest progress of cryoablation therapy of primary liver cancer inChinaZhang Jiren Shj DegangCancer Center Zhujiang Hospital Southera Medical University Guangzhou ChinaIn t11is lecturethe development of cryoablation therapy of liver cancer in China is discussed，which include 6 aspects：1With the help of foreign friendsArgon-helium Cryoablation was introduced into ChinaArgonhelium cryoablation was the integration of more than 20 NASA patents of American hightech，which wasapproved bV FDA in 1998Dudng 19992002200 hospitals in the United States had installed this instrument，which hadreplaced liquid nitrogen and other cryosurgical equipmentThe first endocare cryocare surgical system has been used in zhujiang hospitalthe First Military Medical Universityin 1 999the C：hairman EKLehtinen and Vice，Chairman RHanka of International Biological Therapy Association cameto China for the Center ribbon-cuRingIn China，using endocare cryocarc surgical system，the first cryosurgery began inzhujiang hospital by Peter J LitrupZhang JR and Wang SM in 1 999Endocare cryocare surgical system was named勰Argonhelium Cryoablmion in ChinaIn 1999，by percutaneous cryoablation under CT guidance，the first patient withhepatocellular carcinoma was treated after transcather arterial chemoembolization(TACEl in Zhujiang hospitalOn behalf of collaboration group of Argonhelium cryosurgery in China，we will thank very much for foreign friendshelp and guidance for developing cryotherapy in ChinaThese professors were Peter J Litrrup，Suzy Chosy，DanielRukstalis，Andre，DPeterson，Gregory Groves，Daniel Rukstalis，Go Wakadayash，Winoruanabe and Dan silver,et a1Endocare cryocare surgical system had been used in the oncology center directed by the fellow members of Chineseacademician of medical science。they were、Vu mengchao，Hao xishan，Tang zhaoyou，Wu xianzhongFrom 1 9992007，Endocare Cryocare surgical system had been used in about 70 hospitals in China2The procedure of percutaneous cryoablation under imaging guidanceUnder the guidance of DSA，CT，MR，Laparoscopic，Ultrasound，cryoablation therapy is useful for treating solidtumor,such as lung cancer,liver cancer,glioma，soft tissue tumor,breast cancer,ovary cancer,bone tumors，pancreaticcancerprostate cancer,lenal cancel skin tumorsanalrectal cancel oral tumors。cervical intraepithelial neoplasia，et a1The targeted tissue of cryoablation was observed by imaging study on CT,MRPET and DSAThe clinical results had beenreported in China by several hospitalsTumor markers such as CEAkeP,PSA，CA 19-9 were detected before and aftercryoablation therapy in different kind of tumors3Basic study of targeted cryoablationThe effectiveness of cryosurgery on patients with entity tumor had been confirmed by(1)analysis on cancer anitaalmodels，(2)detection on tumor tissue of patient after cryosurgery，(3)study using immunology and molecular biologymethodsThe most often used cryoablation system was Endocare Cryoeare System produced in USArecently other cryosurgerysystem had been used in chinasuch as Galil Medical System(Israel)in more than 10 hospitalsIn addition，a kind of1122009年世界腫瘤介入學(xué)術(shù)大會匯編1iquid freezing cryoablation system is produced by Qinghua UniversitY,another kind of N2 freezing cryoablation systemis produced by Shanghai Jiaotong UniversitY,which might be found in medical market during 20082009The changes ofcancer cell line before and after cryotherapy were reported by several hospitals111e effects of cryotherapy on the normaltissues were also detected in animal model and patients with tumor,for example，the effects on artery and versus，biliary,pancreas and bronchial tube were also studiedThe changes of targeted tissue of tumor in vivo after cryoablation weredetected and followed up，and the reseeted tissue samples were also analysed in vitro111e impact factors of cryoablation therapy,such as cryoablation time，temperature，blood，argon and helium condition，needle diameters and targeted margin were also studied bv Chinese doctorsIts effectiveness had been confirmed in clinicaloncoiogy,and its standard procedure had been known by every doctorsMore over,the cryoimmunological programs hadbeen carrying on in the fields of DCs，TLs，NK，LAK，and cell factors in clinical oncology，over ten hospitals taking part inthis program4Clinical research of targeted CryoablationApart from surgical resection and interventional procedures，minimally invasive surgery has great significance in thetreatment of HCCCombination of chemotherapy and cryoablation in treating Nonsmall cell lung cancer was performedby Professor ZhaoCombining cryoablation with radiotherapy for treating 250 patients with Non-small cell lung carcinomawas reported by Song huazhi，their results demonstrated that the effects of combing Cryotherapy could prolong the survivalrate of l year and 2 yearsCombining TACE with cryoablation to treat 382 patients with HCC was also reported by Songhuazhi，with their effective rate TACE 328and TACE&Cryoablation 583，respectivelyIn the course of using cryoablation to treat cancer,the collaboration group of Argonhelium cryosurgery in Chinahad summarized the selection protocols of several kinds of treatment techniques for tumor,which included many aspects，such as indications，effect，toxicity，complications，impact to other therapies，relieve pain，the quality of life，reduce thepsychological burden、economic cost(social|family|units)The collaboration group of Argonhelium cryosurgery in China had called for manufacturers to address urgently forthe clinical problems about ablation technology，such as：range，threedimensional shape and clinical guidelines of ablationtarget；effects of physical and biological factors on the target；design the appropriate conformity of ablation target whenusing minimally invasive procedures；targeting position，guidance and navigation；real time monitoring and control of targetablation；evaluation standard of shortterm and longterm after target ablation；the treatment of subclinical and residuallesions；choice of comprehensive treatmentMore over,the collaboration group of Argonhelium cryosurgery in China hadalso stressed the position of ablation therapy in the modem model of tumor treatmentand t11ey had edited three books aboutcryotherapy in the fields of Cryocare targeted cryoablation therapy,Cryosurgery for Cancer and the freezing mechanism ofbiomedical engineeringSince 1999，5 international and 4 national conferences on targeted ablation and minimally invasivetherapy had been hold in China by our committee5Statistic number of cancer patients treated with Argonhelium Cryoablation in ChinaIn Novembet 2007the 1 4t11 Wbrid Congress of cryotherapy had a statistics of l 2 Chinese hospitals about Cllinas useof the United States CryocareTM Cryoablation system for treating tumor patients，with the number reached 1 l，000 cases，ofwhich more than 500 cases had completed in over 10 hospitals individually and some hospitals had completed刪casesMore than 30 kinds of diseases were treated by cryotherapy，among which the numbers of liver cancer and lung cancer werethe most in China compared with any other countries in the world6Review of Iiteratures about Cryocare Surgical treatment of Iiver cancer in ChinaIIl 20th April 2009we use the Chinese key words“l(fā)iver cancer and argon helium”to search articles in the l 9992008National Knowledge Infrastructure(CNKI，CJFD)，and more，use search words“cryoablation and fiver cancerto searchthe literatures of china included in PubMed(MEDLINE)A total of l 19 Chinese literatures of Cryocare treatment for liver cancer were found during the period of 19992008ofwhich ll 8 articles were divided into 14 categories roughlyThey were as followed(1)36 articles about hepatic cryoablationtherapy；(2)14 about ultrasoundguided cryoablation of liver cancer；(3)2 about CT guided cryoablation of liver cancer；(4)1 2 about combined TACE and Cryoablation；(5)9 about comparative study of a variety of minimally invasive therapyand clinical application in primary liver cancer；(6)2 about other interventional techniques combined with argonheliumcryoablation or surgical treatment combined with argonhelium cryoablation of liver cancer；(7)3 about intravenous1132009年世界腫瘤介入學(xué)術(shù)大會匯編anesthesia，monitoring and surgical techniques during intraoperative Cryocare frozen of liver cancer；18)5 articles abouttraditional Chinese and western medicine combined with Cryocare surgical ablation for the treatment of liver cancer；(9)9 articles about side effects and complications of cryoablation with percutaneous liver puncture in the treatment of livercancer；(10)l 3 of Nursing；(11)5 about postoperative imaging to evaluate the efficacy；(功3 about reasonable alternation andevaluation of cryoablation in Iiver cancer；4 articles of laboratory studies about immunology，liver function and otheraspects of the impact of cryoablation in liver cancer；04)l article about other aspects of the pilot studyThe statistics ofsurvival rate of 1iver cancer patients after cryoablation at l，2，3，4，5 years were also analyzed，which were 348985，25-63642583individuallybut without survival rate of 4 and 5 yearsEf佬ct of cryoablation based combined therapywas better than simple cryoablation or TACE，with the survival rate of combined cryoablation at l，2 years was 83and6 189 17individuallyIn addition，5 l 3 literatures about frozen treatment of liver cancer were included in Medline，in which 40 articles werewritten by Chinese authorsIn 2008，Xu KC，Niu LZ，Hu YZ，et al had summarize the survival rate of 326 cases of livercancer by percutaneous cryosurgery(Argon-helium，endocare cryocare system produced in USA)at l，2，3，4，5 year,whichwere 78，62，4 l，34，23，individuallyIn 2006，Chen SG，Zhang SM，Zhao HT，et a1had compared the survivalrate of liver cancer patients between 73 cases of cryosurgery-based combined therapy(1iquid nitrogen，LCS一2000 producedby Cryogenic Technology L1rD，UK)and 239 cases of 1ACEoriented combined therapy，with 1，3，5 years survival rate644，384，274；and 751，29O，lO0，individuallyIn 2002，Rui JA，Wang SB，Chen SG，et a1had reportedtheir results of 1 9 1 cases of surgical resection and 70