术中超声引导放射性125I粒子组织间植入治疗胰腺癌

目的探讨术中超声引导放射性~(125)Ⅰ粒子组织间植入治疗胰腺癌的手术方法、近期疗效和副反应。方法27例无法切除的晚期胰腺癌,行术中超声引导~(125)Ⅰ粒子组织间植入治疗,11例行胃肠或胆肠短路术。腹部正中切口,暴露肿瘤,利用术中超声探及肿瘤大小、范围,确立进针方向和范围。插植粒子针边界外放1.0～1.5 cm,避开血管和胰管,间隔1cm。Mick枪后退式植入粒子,粒子间隔1cm。~(125)Ⅰ粒子活度为0.40～0.70 mCi/颗,D_(90)为110～160 Gy。6例术后4周加外放疗,2～3 Gy/次,5次/周,总剂量39～50 Gy。5例术后顺铂 吉西他滨化疗,2～4周期。结果20例伴有上腹部疼痛患者,粒子治疗后有17例疼痛完全或部分缓解,有效率85%,显效时间1～30 d,中位起效时间5 d。全组局部控制率为74%,Ⅱ Ⅲ期1、2年生存率分别为25%、15%,中位生存时间8个月,Ⅳ期1年生存率为8%,中位生存时间5个月。3例术后1个月复查时发现5颗粒子迁徙到肝脏。3例术后6周到6个月出现乳糜瘘,2例对症处理后缓解,2例复发合并上消化道出血,没有感染和胰瘘等并发症。结论放射性~(125)Ⅰ粒子组织间植入治疗胰腺癌具有很好的姑息止疼疗效,部分局部晚期患者可获得长期生存,而且并发症发生率较低。     

放射性粒子植入治疗中晚期胰腺癌疗效分析

目的:探讨125I放射粒子植入术治疗手术无法切除的胰腺癌的疗效。方法:选择胰腺癌患者50例。内放射治疗组30例,肿瘤内部125I放射粒子植入,有梗阻症状者,加行胆-肠吻合术和胃-空肠吻合术;对照组20例,均行单纯剖腹探查或胆-肠吻合术和/或胃-空肠吻合术。观察肝肾功能、总胆红素变化;肿瘤大小变化;并发症发生情况;腹痛、背痛变化等。结果:两组患者总胆红素术后4周时均接近正常,肝功能明显改善,手术前后比较均具有统计学意义;粒子植入组患者手术前后腹痛、腰痛改善明显。有效率100%(30/30),完全缓解率97%;粒子植入组肿瘤直径有缩小趋势,对照组无明显变化;两组患者均无吻合口瘘、胆瘘、胰瘘、腹腔出血和腹腔感染。结论:125I粒子植入对不可切除的胰腺癌具有确定疗效,不仅可以明显延长患者生存期,提高生活质量,且对胰腺癌引起的疼痛有明显的缓解效果。     

含洛铂方案经肝动脉化疗栓塞联合125I粒子植入术治疗不能手术的中晚期肝癌的疗效观察

背景与目的：应用经肝动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)治疗肝癌存在着坏死率低的不足,¹²⁵I粒子植入术作为一项新的放疗技术具有靶向性强的优点。本研究旨在观察含洛铂方案TACE联合¹²⁵I粒子植入术对不能手术的中晚期肝癌患者的临床疗效及3年生存情况,为肝癌的临床治疗提供参考。方法：前瞻性研究设计,选取2010年1月—2013年1月郑州大学附属肿瘤医院收治的中晚期肝癌患者102例,随机数字表法分为观察组和对照组,每组51例。对照组患者接受含洛铂方案TACE治疗,观察组患者在对照组治疗方案的基础上加用125I粒子植入术。观察两组患者治疗前和治疗后6个月的甲胎蛋白(alphafetoprotein,AFP)、肝功能指标、细胞免疫指标变化情况及肿瘤转移情况,比较两组患者治疗后的近期疗效及3年生存率,并记录随访期内不良反应发生情况。结果：治疗前两组患者一般资料及临床相关指标比较差异均无统计学意义(P均>0.05)。经不同方案治疗后,观察组近期有效率(86.3%)显著高于对照组(68.6%);治疗后6个月,两组患者血清AFP检测水平较治疗前明显降低,其中观察组患者血清AFP水平下降幅度显著大于对照组(P<0.05);两组患者肝功能指标及细胞免疫指标比较差异无统计学意义(P>0.05);观察组治疗后6个月远处转移的发生率(7.8%)明显低于对照组(23.5%),术后1、2和3年内生存率分别为68.6%、43.1%和31.4%,均明显高于对照组(41.2%、29.4%和13.7%),差异均有统计学意义(P均<0.05);两组患者随访期间均未出现严重并发症。结论：含洛铂方案TACE联合¹²⁵I粒子植入术治疗不能手术的中晚期肝癌的疗效确切,与单纯含洛铂方案TACE治疗相比优势明显,能更有效的控制肿瘤转移,提高生存率,值得在临床推广应用。     

Continuous and low-energy 125I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth

Background

Iodine 125 (¹²⁵I) seed irradiation is an effective treatment for unresectable pancreatic cancers. However, the radiobiological mechanisms underlying brachytherapy remain unclear. Therefore, we investigated the influence of continuous and low-energy ¹²⁵I irradiation on apoptosis, expression of DNA methyltransferases (DNMTs) and cell growth in pancreatic cancers.

Materials and methods

For in vitro ¹²⁵I seed irradiation, SW-1990 cells were divided into three groups: control (0 Gy), 2 Gy, and 4 Gy. To create an animal model of pancreatic cancer, the SW 1990 cells were surgically implanted into the mouse pancreas. At 10 d post-implantation, the 30 mice with pancreatic cancer underwent ¹²⁵I seed implantation and were separated into three groups: 0 Gy, 2 Gy, and 4 Gy group. At 48 or 72 h after irradiation, apoptosis was detected by flow cytometry; changes in DNMTs mRNA and protein expression were assessed by real-time PCR and western blotting analysis, respectively. At 28 d after ¹²⁵I seed implantation, in vivo apoptosis was evaluated with TUNEL staining, while DNMTs protein expression was detected with immunohistochemical staining. The tumor volume was measured 0 and 28 d after ¹²⁵I seed implantation.

Results

¹²⁵I seed irradiation induced significant apoptosis, especially at 4 Gy. DNMT1 and DNMT3b mRNA and protein expression were substantially higher in the 2 Gy group than in the control group. Conversely, the 4 Gy cell group exhibited significantly decreased DNMT3b mRNA and protein expression relative to the control group. There were substantially more TUNEL positive in the ¹²⁵I seed implantation treatment group than in the control group, especially at 4 Gy. The 4 Gy seed implantation group showed weaker staining for DNMT1 and DNMT3b protein relative to the control group. Consequently, ¹²⁵I seed implantation inhibited cancer growth and reduced cancer volume.

Conclusion

¹²⁵I seed implantation kills pancreatic cancer cells, especially at 4 Gy. ¹²⁵I-induced apoptosis and changes in DNMT1 and DNMT3b expression suggest potential mechanisms underlying effective brachytherapy.     

消融或联合125I粒子植入术治疗肾癌11例报告

背景与目的:射频多极针消融和近距离放疗近年来被广泛用于治疗肝癌和前列腺癌等实体肿瘤。本研究探讨用射频多极针消融或联合125I粒子植入术治疗肾癌患者的可行性。方法:2000年6月至2004年2月,采用射频多极针消融或联合植入放射性125I粒子治疗原发性肾癌患者11例,共13个肿瘤结节。其中孤立肾6例,肾癌合并对侧输尿管结石导致肾功能严重受损2例,双侧肾肿瘤1例,高龄患者不能耐受手术2例。对这13个肿瘤结节,分别采用开放手术、单纯消融、消融联合肿瘤周边植入放射性125I钛壳粒子进行治疗。结果:11例患者,术后随访6～46个月,平均27个月。1例术后4个月死于心肌梗塞;2例分别于术后7、11个月肿瘤复发,再次消融;1例因尿毒症间断透析治疗;7例患者肾功能正常。结论:消融或125I粒子植入术是治疗孤立肾、双肾肿瘤和高危不能耐受手术患者的一种可供选择的方法。     

125I粒子联合化疗治疗非小细胞肺癌

目的探讨125I粒子联合化疗治疗非小细胞肺癌(NSCLC)的临床效果及并发症.方法治疗组(42例)采用CT引导下、PD(处方剂量)=8～10Gy/h植入125I粒子,3 d后紫杉醇+DDP静脉化疗,对照组(46例)单纯紫杉醇+DDP静脉化疗,药物剂量与治疗组参考标准相同.2个月后观察治疗效果(CR,PR,SD,PD).根据生活质量量表EORTC QLQ-C30评价生活质量.结果技术成功率100%,术后随访率100%.治疗组CR 4例(9.5%),PR 14例(33.3%),SD 20例(47.6%),PD4例(9.5%),CR+PR为42.9%;对照组CR 1例(2.2%),PR 8例(17.4%),SD 22例(47.8%),PD 15例(32.6%),CR+PR为19.6%,治疗组总有效率明显高于对照组(P＜0.05).结论对于非小细胞肺癌,125I粒子联合化疗具有优势互补作用,有利于短期内降低肿瘤负荷,提高近期疗效.     

Efficacy of therapy for hepatocellular carcinoma with portal vein tumor thrombus: chemoembolization and stent combined with iodine-125 seed

The purpose of this study is to analyze the safety and clinical efficacy of transcatheter arterial chemoembolization (TACE) combined with portal vein stent and 125I implantation for the treatment of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma. Fifty-six patients from our department diagnosed with advanced hepatocellular carcinoma with PVTT between January 2008 and December 30, 2010 were divided into two groups. Patients in Group A were treated with TACE and portal vein stent; patients in Group B were treated with TACE, portal vein stent and 125I implantation. The success rate of TACE with portal vein stent and 125I implantation was 100%, with no severe surgery-related complications. After an 8 mo follow-up, the total clinical benefit rates were 56.7 and 88.5% for Groups A and B, respectively (p < 0.05). The median survival times (mOS) for the two groups were 5.7 and 8.9 mo, respectively (p < 0.05). The median time of progression (mTTP) of the two groups were 5.3 and 7.9 mo, respectively (p < 0.05). The 2, 6, 8, 12 and 18 mo patency rates in Group A were 100, 93.3, 83.3, 53.3 and 36.6%. Those in Group B were 100, 100, 92.3, 84.6 and 80.7%. The 2, 6 and 8 mo patency rates showed no statistical differences (p > 0.05), but the 12 and 18 mo rates did (p < 0.05). Our results suggest that TACE combined with portal vein stent and 125I implantation are both safe and effective, and 125I implantation can further postpone the restenosis of the portal vein effectively.     

复发转移胸壁肿瘤CT引导125I粒子治疗疗效初探

目的 初步探讨CT引导¹²⁵I粒子植入治疗复发或转移胸壁肿瘤的可行性和疗效。
方法 回顾分析2004-2012年间23例复发或转移胸壁恶性肿瘤患者接受CT引导¹²⁵I粒子植入治疗资料。术前计算机治疗计划系统行三维治疗计划,确定粒子数目、空间分布,术后即刻CT扫描剂量验证。90%靶体积接受的剂量为100~160 Gy (中位数130 Gy),¹²⁵I粒子活度为(1.85~2.89)×10⁷ Bq (中位数2.63×10⁷ Bq)。植入粒子8~269颗(中位数53颗)。局部控制率和生存率计算采用Kaplan-Meier法。
结果 随访率100%,随访时间满3、5年者分别为11、8例。23例患者中4例完全缓解、12例部分缓解。1、3、5年局部控制率分别为82%、62%、62%,肿瘤特异生存率分别为61%、45%、45%,总生存率分别为58%、58%、39%。疗后1例患者出现轻中度臂丛神经损伤,6例出现1、2级皮肤损伤。
结论 初步结果显示CT引导¹²⁵I粒子植入治疗复发或转移胸壁肿瘤安全有效。     

On a method of dosimetry planning and implantation of 125I for interstitial irradiation of malignant gliomas

Utilizing a treatment concept geared to the cell cycle of the glioma, a CT determined tumor volume and boundaries, ¹²⁵I dosimetry data and a reference probe template system, it is now feasible to produce a volume implant of an intracranial mass based on prospective planning with accurate postimplant correspondence. The cell cycle oriented treatment plan is felt perhaps to be more beneficial in the treatment of the highly malignant glioblastoma, considering its wide range of cell cycle times, large irregular volumes and large dormant segment, than would be a similar isotope source delivering a high-dose rate, but short-term course irradiation. Seeds are contained within Lexan tubes, thereby allowing accurate assessment of postoperative dosimetry planning, negating seed migration and possible `cold spots' within a volume implant as would be noted with unrestrained seeds. The implant described in this communication is designed to remain in place for approximately 20 months, a period of time well beyond the life expectancy of any group of failed glioma patients. Although ultimately the system may prove most beneficial in newly diagnosed glioblastomas, the current trial in patients having previously undergone 5–6000 rads of external beam therapy is not considered hazardous to surrounding brain.     

125 I粒子植入治疗鼻咽癌的基础和临床研究

放疗是目前治疗鼻咽癌的主要手段,但鼻咽癌放疗后的病灶残留及复发转移的处理仍是一个棘手的问题。125 I粒子植入作为综合治疗中的一员,其治疗鼻咽癌的可行性在细胞学、动物学实验研究中得到证实,并逐渐应用于鼻咽癌放疗后病灶残留、复发转移等方面,且临床治疗效果得到认同。     

CT引导下经皮穿刺植入放射性125I粒子治疗肺癌的临床应用

目的 探讨CT引导下经皮穿刺植入放射性125I粒子的肺癌治疗方法,观察临床疗效和不良反应.方法 于2004年6月-2005年10月,经CT引导125I粒子植入治疗肺癌32例.所有病例均行术前TPS制定治疗计划,术后质量验证.全部患者均植入0.5 mCi-1.0 mCi的放射性粒子,12-60颗.结果 植入病例全部成功,无死亡,部分出现气胸、出血,术后1周复查外周血象、1月复查CT及临床观察无毒副反应,术后定期复查CT,未出现放射损伤症状,未发现粒子脱落或游走等并发症.CR 22.58%、PR 61.29%、SD 12.9%、PD 3.2%.中位生存期大于12个月.结论 CT引导下经皮穿刺放射性125I粒子近距离照射治疗肺癌安全、有效,并且创伤小、并发症少.     

CT引导下放射性125I粒子植入治疗恶性肿瘤的临床研究

目的:探讨CT引导下放射性125I粒子植入治疗恶性肿瘤的疗效。方法:回顾性分析2007年7月至2008年12月恶性肿瘤68例,均行125I粒子植入治疗。植入前用三维治疗计划系统计算术中所需125I粒子的总活度及粒子的数量,CT引导下植入病灶中,粒子活度为0.6-0.8mCi,处方剂量90-110Gy,术后验证粒子植入剂量分布。植入后复查并随访,统计有效率、局部控制率及不良反应等情况。结果:68例患者粒子植入均顺利完成。6个月有效率(包括完全缓解及部分缓解)88.2%。术后随访6-24个月,局部控制率为76.5%,术中4例出现气胸,经治疗好转,术后出现粒子迁移3例,无严重并发症发生。结论:CT导向125I粒子植入治疗恶性肿瘤是一种安全而有效的方法。     

手术加125I粒子永久性植入治疗肺癌单发脑转移瘤的临床疗效及放射性脑损伤程度的研究

背景与目的:研究证实全脑放射治疗可引起放射性脑损伤,因此,探索一条能取代全脑照射而不影响疗效的新的治疗方法十分必要。本研究的目的就是评价手术加125I粒子永久性组织间植入治疗非小细胞肺癌单发脑转移瘤的疗效及放射性脑损伤程度。方法:将67例非小细胞肺癌单发脑转移瘤随机分为:手术加125I粒子植入组(植入组)32例(47.8%);全脑加小野照射组(常规组)35例(52.2%)。所有患者均经病理证实为非小细胞肺癌,其中鳞癌42例,腺癌25例。CT或MRI证实67例患者颅内有转移灶且为单发。植入组行局部脑转移瘤切除术,术后根据肿瘤大小、部位、125I粒子排列距离和每粒粒子剂量大小确定插入粒子数量。粒子植入部位:在肿瘤切除部位及周围组织或手术区域肿瘤可能残存或复发部位。常规组先行全脑照射,2～3Gy/次,5次/周,照射至剂量为30～39Gy/3～4周后缩小野加量,总剂量达45～55Gy/5～6周。结果:植入组局控率、复发率、中位复发时间分别为96.9%、15.6%和9个月;常规组分别为82.9%、17.1%和7个月,两组比较均无统计学意义(P>0.05)。植入组的中位生存时间、1年生存率、1年死亡率分别为12个月、40.6%以及28.1%;常规组为9个月、31.4%以及37.1%,两组比较均有显著性差异(P<0.05)。植入组急性放射性反应明显轻于常规组,其放射性损伤也     

放射性^125I粒子植入联合内分泌治疗早期前列腺癌

目的：探讨经会阴超声引导放射性^125I粒子植入联合去势治疗早期前列腺癌疗效和不良反应。方法：39例早期前列腺癌实施经会阴超声引导和适时计划指导放射性^125I粒子植入治疗,7例粒子术前行去势术,21例粒子植入后同时行去势术,11例粒子治疗后联合药物去势治疗。粒子治疗的匹配周边剂量（matched peripheral doses,MPD）为145—160Gy,尿道剂量低于400Gy。^125I粒子活度0．35—0．50mCi,中位植入69颗（19—97颗）。结果：失败标准为前列腺特异抗原（prostate specific antigen,PSA）治疗后升高〉4ng／ml,≤〈4ng／ml为生物化学无进展生存（biochemical disease—free survival,BDFS）。全部患者顺利完成粒子植入术。36例粒子治疗后达到BDFS,3例分别在粒子治疗后6、8和36个月PSA升高,2例行内分泌治疗,1例行外放疗联合内分泌治疗。2年和3年BDFS分别为94．8％（37／39）和92．3％（36／39）。粒子植入治疗后Ⅰ级和Ⅱ级直肠不良反应发生率分别为5．1％（2／39）和7．7％（3／39）,没有Ⅲ级和Ⅳ级直肠反应。粒子植入治疗后Ⅰ级、Ⅱ级和Ⅲ级尿道不良反应发生率分别为53．8％（20／39）、17．9％（7／39）和2．6％（1／39）,对症处理好转。2例粒子移位,没有相关并发症。结论：经会阴超声引导放射性^125I粒子植入治疗前列腺癌具有安全、微创、并发症发生率低等优点。     

^125Ⅰ前列腺放射粒子植入术并发症分析

目的 探讨125I前列腺放射粒子植入术治疗前列腺癌的效果和并发症. 方法 前列腺癌患者72例,临床分期T2bN0M0至T3aN0M0期63例,T3N0M19例.采用超声引导下125I前列腺放射粒子植入术治疗.术后进行雄激素全阻断辅助治疗.观察术后并发症和临床疗效. 结果 手术时间1～2 h,4～6 d拔除尿管出院.术后随访6～53个月,平均17个月.CR 52例,PR 12例,SD 6例,PD2例.本组病例PSA无进展生存率为97.2%(70/72).Ⅰ级排尿症状47例,Ⅱ级排尿症状25例,无Ⅲ级和Ⅳ级排尿症状发生.伴有直肠刺激症状21例,多为轻度.术后严重出血性直肠炎1例,尿道直肠瘘1例,为同一患者,行结肠造口术和膀胱造瘘术.死亡1例. 结论 125I前列腺放射粒子植入术治疗前列腺癌疗效肯定、创伤小,尤其适合于不能耐受前列腺癌根治术的高龄前列腺癌患者.副作用主要为尿路和直肠症状,多为轻度和自限性的.     

Synergistic antitumor effect of adenovirus-mediated hING4 gene therapy and (125)I radiation therapy on pancreatic cancer

Pancreatic cancer has a poor prognosis, even with surgery. ING4 is a member of the inhibitor of growth (ING) tumor suppressor family that has potent inhibitory effects on a variety of tumors; meanwhile, radiotherapy is a common adjunctive therapy for pancreatic cancer. Prior to this study, the effectiveness of a combination of ING4 gene-therapy and radiotherapy against pancreatic cancer had been unknown. In this study, we demonstrated that either ING4 or ¹²⁵I radiotherapy treatment could induce Panc-1 pancreatic cancer cell growth suppression and apoptosis in vitro. Furthermore, both treatments inhibited tumor growth and angiogenesis of Panc-1 pancreatic cancer subcutaneously xenografted in vivo. Moreover, the combination therapy had a synergistic effect.     

Identification of residual breast tumour localization after neo-adjuvant chemotherapy using a radioactive 125 Iodine seed

Introduction

The use of neo-adjuvant chemotherapy has increased in the treatment of loco-regionally advanced primarily operable breast cancer. As a result of improved neo-adjuvant chemotherapy regimes the number of clinical as well as radiological responses have increased. In case of a complete response it is difficult to identify residual disease and to perform an adequate radical breast-conserving surgery. Therefore localization of the original tumour bed is mandatory. In this study we propose a novel technique with a seed containing radioactive 125 Iodine (¹²⁵I). The ¹²⁵I has a half-time of 60 days and is therefore still recognisable with a gamma probe after admittance of several courses of neo-adjuvant chemotherapy.

Material and Methods

In the period from July 2003 and November 2008, 47 consecutive patients had successful ¹²⁵I seed localization of a breast tumour before starting neo-adjuvant chemotherapy.

Results

The overall clinical response rate to neo-adjuvant chemotherapy was 100%. Complete clinical response occurred in 34 patients, partial clinical response occurred in 13 patients. Complete radiological response occurred in 18 patients, partial radiological response occurred in 29 patients. The initial surgical treatment consisted of breast-conserving surgery for all 47 patients, after a mean of 170 days (range: 70–220) after ¹²⁵I seed localization. In 19 patients pathology revealed no residual tumour, 23 patients showed a partial response. Only 3 lumpectomies were irradical.

Conclusion

This study has shown that ¹²⁵I seed localization is a novel and highly successful technique in localizing the tumour bed in patients who receive neo-adjuvant chemotherapy for breast cancer leading to a high percentage of radical margins in case of breast-conserving surgery.     

放射性125I粒子治疗老年人晚期恶性肿瘤的临床研究

目的 探讨CT引导下放射性123I粒子植入治疗老年人晚期恶性肿瘤患者的疗效.方法 收集同期78例老年晚期恶性肿瘤患者,采取自愿接受治疗原则将其分为两组.治疗组41例采用CT引导下放射性125I粒子植入治疗,粒子活度为29.6 MBq,处方剂量90～110Gy;对照组37例采用最佳支持治疗;所有患者均复查并随访,观察其近期疗效、生存质量及不良反应等情况.结果 治疗组有效率为92.7％(38/41),疾病控制率97.6％(40/41),对照组有效率0,疾病控制率16.2％(6/37).治疗组生存质量高于对照组(P＜0.05),未见严重不良反应.结论 放射性125I粒子植入治疗老年人晚期恶性肿瘤是一种安全而有效的方法,能提高患者生存质量.