Cryosurgery with combination of (125)iodine seed implantation for the treatment of locally advanced pancreatic cancer

OBJECTIVE: To study the therapeutic value of cryosurgery with combination of (125)iodine seed implantation for locally advanced pancreatic cancer. METHODS: Thirty-eight patients with locally advanced pancreatic cancer were enrolled in this study. The diagnosis was confirmed by pathology in 31 patients. Ten patients had metastases of the peripancreatic lymph node and eight had liver metastases. The therapy included cryosurgery, which was performed intra-operatively or percutaneously under guidance of ultrasound and/or computed tomography (CT), and (125)iodine seed implantation, which was performed during cryosurgery process or post-cryosurgery under the guidance of ultrasound and/or CT. RESULTS: Eleven patients received intra-operative cryosurgery and 27 received percutaneous cryosurgery. Fourteen patients underwent two procedures of cryosurgery and three underwent three procedures of cryosurgery. (125)Iodine seed implantation was performed during the freezing procedure in 29 patients and within 3-7 days after cryosurgery in nine patients under ultrasound and CT guidance. Fifteen patients, of whom 13 had metastases of peripancreatic lymph nodes or liver received regional chemotherapy. At 3 months after therapy, a CT follow-up was performed to estimate the tumor response to therapy. Most of the patients had varying degrees of tumor necrosis. A complete response of the tumor was seen in 23.6% of patients, a partial response in 42.1%, stable disease in 26.3% and progressive disease in 7.9%. The adverse effects associated with cryosurgery mainly included pain of the upper abdomen and increased serum amylase activity. Acute pancreatitis was seen in five patients, one of whom presented a severe type of pancreatitis. During the followed-up of a median of 16 months (range of 5-37) median overall survival was 12 months, 19 patients (50.0%) survived for 12 months or longer and four survived for 24 months or longer. CONCLUSION: As it is far less invasive than conventional pancreas resection and entails a low rate of adverse effects, cryosurgery should be the choice modality for most patients with locally advanced pancreatic cancer. (125)Iodine seed implantation can destroy residue survival cancer cells after cryosurgery. Hence, combination of both modalities has a complementary effect.     

Radical treatment of stage IV pancreatic cancer by the combination of cryosurgery and iodine-125 seed implantation

AIM: To investigate the therapeutic effect of radical treatment and palliative treatment in stage IV pancreatic cancer patients.METHODS: 81 patients were enrolled in the study. Radical treatment was performed on 51 patients, while 30 patients were put under palliative treatment. The procedural safety and interval survival for stage IV pancreatic cancer (IS-IV) was assessed by almost 2.5 years of follow-ups. The IS-IV of patients under the two kinds of treatment, and the effects of treatment timing and frequency on IS-IV, were compared.RESULTS: The IS-IV of patients who received radical treatment was significantly longer than those who received palliative treatment (P < 0.001). The IS-IV of patients who received delayed radical or palliative treatment was longer than those who received accordingly timely treatment (P = 0.0034 and 0.0415, respectively). Multiple treatments can play an important role in improving the IS-IV of patients who received radical treatment (P = 0.0389), but not for those who received palliative treatment (P = 0.99).CONCLUSION: The effect of radical treatment was significantly more obvious than that of palliative treatment, and multiple radical treatments may contribute more to patients than a single radical treatment.     

^125Ⅰ粒子组织间植入治疗胰腺癌的实验研究

目的探讨125I粒子组织间植入治疗胰腺癌的有效性。方法Balb/c裸鼠腋下接种人胰腺癌SW1990细胞。按植入剂量不同将成瘤后裸鼠分为对照组和50Gy、100Gy、150Gy、200Gy组,每4d测量肿瘤体积,21d后处死裸鼠,称瘤重,计算肿瘤抑制率,常规病理检查,TUNEL法检测凋亡细胞。结果对照组、50Gy组、100Gy组、150Gy组及200Gy组抑瘤率分别为0、(42.8±16.2)%、(55.1±22.3)%、(72.8±12.8)%及(75.6±8.6)%;以粒子为中心的肿瘤坏死面积分别为(6.3±2.1)%、(20.8±3.2)%、(36.3±3.1)%、(64.1±2.8)%及(82.6±3.8)%;相对凋亡指数分别为1、2.07±0.57、2.75±0.33、4.64±0.45及7.04±0.34,各治疗组均显著高于对照组(P<0.05)。结论125I粒子组织间植入可显著抑制肿瘤生长,放射粒子具有直接杀死肿瘤细胞和诱导凋亡双重作用。     

Intraoperative radiofrequency ablation combined with 125 iodine seed implantation for unresectable pancreatic cancer

AIM: To evaluate the feasibility, efficacy and safety of intraoperative radiofrequency ablation (RFA) combined with 125 iodine seed implantation for unresectable pancreatic cancer. METHODS: Thirty-two patients (21 males and 11 females) at the age of 68 years (range 48-90 years) with unresectable locally advanced pancreatic cancer admitted to our hospital from January 2006 to May 2008 were enrolled in this study. The tumor, 4-12 cm in diameter, located in pancreatic head of 23 patients and in pancreatic body...     

超声内镜引导125I粒子组织间植入治疗晚期胰腺癌的疗效及粒子移位分析

目的分析胰腺癌超声内镜（EUS）引导下^125I粒子种植术治疗晚期胰腺癌的肿瘤变化及粒子移位，并评价其治疗效果。方法对17例不能手术切除的中晚期胰腺癌患者行EUS引导下放射性^125I粒子内照射治疗。所有患者治疗前均参照治疗设计系统估算期望植入粒子数量。治疗后每月复查，观察治疗前、后肿瘤变化及粒子移位、脱落等情况。结果17例患者均经EUS植入^125I粒子成功。治疗前肿瘤最大长径平均值为5．4cm（3．7～9．0cm），平均植入粒子数量为27颗，平均每次植入粒子中位数为14（7～24）颗，平均植入2次。平均单颗粒子的放射性活度为（0.689±0．016）mCi。治疗后平均随访4．8个月（2～14个月）。治疗后3个月评估疗效，部分缓解5例（29．4％），疾病稳定7例（41．2％），进展恶化5例（29．4％）。治疗后腹部平片示5例（29．4％）出现粒子丢失移位。1例脾区移位，1例肝脏移位，3例肠腔移位。治疗后粒子丢失4例。1例出现脾脏及左膈下囊肿。结论EUS引导下^125I粒子内照射治疗晚期胰腺癌，可使粒子照射区域内病灶明显萎缩。但需注意放射性粒子对周围脏器的损害及粒子脱落移位等并发症的发生。     

冷冻加放射性碘粒子植入治疗局部进展型胰腺癌

目的 探讨术中或经皮冷冻加125I粒子植入对局部进展型胰腺癌的治疗价值.方法 对38例经过综合评价被认为不能接受手术切除的局部进展型胰腺癌采用手术中或经皮冷冻加125I粒子植入方法进行治疗.125I粒子植入系在手术直视下或在超声或CT引导下经皮穿刺完成.8例患者人院前接受过4～6个周期化疗.治疗后3个月做CT评价肿瘤治疗反应.结果 11例患者接受术中冷冻,27例接受经皮冷冻,其中14例接受2次冷冻,3例接受3次冷冻.29例在冷冻的同时行肿瘤内125I粒子植入,9例在术后于超声或cT引导下行125I粒子植入.15例(其中13例伴胰周淋巴结或肝转移)患者行区域动脉化疗.CR、PR、SD和PD分别为9例、16例、10例和3例.20例(52.6%)患者出现上腹痛,16例(42.1%)血清淀粉酶升高,5例(13.2%)并发AP,其中1例为SAP,均经保守治疗痊愈.无治疗相关性死亡.随访5～37月,中位生存期12个月,6、12、24和36个月总生存率分别为94.7%、49.4%、21.8%和5.4%.接受化疗患者的6、12、24和36个月生存率分别为93.3%、26.6%、0和0,未接受化疗者生存率分别为95.6%、65,9%、19.8%和9.9%,两组相差显著(P＜0.01).生存期最长的2例分别为31和37个月,目前无任何复发证据.病死29例,12个月内共病死15例.结论 对大多数胰腺癌尤其不能手术切除患者,冷冻治疗有良好疗效,不良反应发生率较低.在冷冻同时或其后加用125I粒子植入,与冷冻治疗有相辅相成之效.     

经皮埋置125碘籽治疗不能切除性胰腺癌

目的 研究经皮埋置^125碘籽对不能手术切除性胰腺癌的治疗价值。方法 在B超监视下，经皮穿刺注入^125碘籽入胰肿瘤内。按肿瘤大小，注入30～80粒，放射活性15～40mCi。结果 13例均为不能手术切除的进展期胰腺癌，经^125碘籽局部埋置后，69．2％的病例腹痛改善，38．5％的病例腹痛几乎完全消失；53．8％的病例肿瘤缩小；中位生存期13个月，6、12、18和24个月生存率分别为92.3％、53．8％、38．5％和15．3％。结论 经皮植入^125碘籽对病人的侵袭性小，而取得的结果与常规手术、放化疗的结果大体相似，可作为不能切除性胰腺癌的治疗手段。     

Treatment of portal vein tumor thrombus using ~(125)Iodine seed implantation brachytherapy

We reported two cases of liver metastasis with portal vein tumor thrombus that developed after liver transplantation for hepato cellular carcinoma (HCC). Both the patients were women aged 43 and 55 years, who had liver metastasis and portal vein tumor thrombus formation after liver transplantations for HCC. For the treatment of portal vein tumor thrombus, 125I seeds were implanted into the hepatic tissue under the guidance of preoperative computed tomography (CT) images with a total radiation dose of 130 Gy...     

超声内镜引导下定向植入放射性125Ⅰ粒子治疗胰腺癌的临床研究

目的探讨超声内镜引导下定向植入放射性粒子治疗胰腺癌的临床可行性。方法在超声内镜引导下对10例手术无法切除的胰腺癌患者行125I粒子定向植入术,通过19G穿刺针植入粒子。首先,根据肿瘤大小确定植入粒子数量。其次,在超声内镜引导下植入粒子。术后1个月进行CT随访。结果每例患者植入的粒子数量4~12枚不等。植入术均安全完成,术后未发生严重并发症。9例疼痛患者3d内均感缓解。术后1个月时随访,4例为疼痛部分缓解,3例为疼痛轻度缓解;1例肿瘤部分缓解,7例患者肿瘤无明显进展。1例患者2个月后随访发现肝脏转移,另1例患者3个月后病情恶化死亡。结论超声内镜引导下定向植入放射性粒子安全、可靠,并发症少,值得推广。     

放射性125I粒子植入术治疗局部非小细胞肺癌的疗效

目的探讨放射性碘125(¹²⁵I)粒子植入治疗局部非小细胞肺癌(NSCLC)的近远期疗效。 方法选择2015年1月到2018年1月无锡市第五人民医院收治的67例局部NSCLC患者作为研究对象,按照随机数字表法将其随机分为研究组32例和对照组35例,对照组采取紫杉醇联合顺铂静脉滴注方案进行化疗,研究组在对照组基础上采取放射性¹²⁵I粒子植入术治疗,比较两组临床疗效,比较两组治疗前后癌胚抗原(CEA)、细胞角质素片段抗原21-1(CYFRA21-1)、糖类抗原125(CA125)水平及癌症患者生活质量核心量表(EORTC QLQ-C30)评分,比较两组治疗期间不良反应发生情况及近远期随访生存情况。 结果研究组治疗后ORR为81.25%显著高于对照组57.14%,差异有统计学意义(P<0.05)。研究组治疗后CYFRA21-1、CA125显著低于治疗前及对照组治疗后(P<0.05);两组治疗后CEA组内比较显著低于治疗前(P<0.05)。研究组治疗后躯体症状评分显著低于治疗前及对照组治疗后(P<0.05);两组治疗后总体功能、总体健康评分显著高于治疗前(P<0.05)。研究组不良反应总发生率为53.13%,与对照组37.14%比较,差异无统计学意义(P>0.05)。研究组半年、1年、2年存活率分别为96.88%、87.50%、75.00%,显著高于对照组半年、1年、2年存活率82.86%、65.71%、48.57%,差异有统计学意义(Log-Rank＝5.124,P＝0.024)。 结论放射性¹²⁵I粒子植入治疗可显著提高局部NSCLC患者近远期生存率,改善患者体内血清肿瘤标志物水平,且安全性良好,临床价值较高。     

经皮冷消融治疗局部进展性胰腺癌的可行性

目的 前瞻性观察经皮冷消融治疗的不良反应、肿瘤变化及近期疗效,探讨该技术治疗局部进展性胰腺癌的可行性.方法 2008年9月至2009年9月共59例局部进展性胰腺癌患者采用氩/氦为基础的冷冻系统,在超声引导下行经皮冷消融治疗.将冷冻探针插入胰腺肿块的中心,做2次循环冷冻,每次冷冻5 min,温度为-160℃,然后复温,持续10 min.检测治疗前和治疗后7 d的血清淀粉酶活性;冷消融后每4～6周行CT扫描评价肿瘤变化;应用Kaplan-Meier法计算生存率.结果 59例患者共有76个活检证实的肿瘤,位于胰头部56个、胰体部7个、胰尾部13个.肿瘤中位大小4.5 cm,19例伴肝转移.术后发生腹痛45例(76.3%),发热29例(49.2%),血淀粉酶升高34例(57.6%),严重并发症(腹腔内出血、胰漏、肠梗阻和冷冻探针针道转移)5例(8.5%),无冷消融相关性死亡.中位住院时间21 d.2例(3.4%)获得完全缓解,23例(39.0%)获得部分缓解,30例(50.8%)疾病稳定,4例(6.8%)疾病进展.中位存活期8.4个月;3、6、12个月存活率分别为89.7%、61.1%和34.5%.结论 超声引导下的经皮冷消融是一种安全可行的局部进展性胰腺癌微创治疗技术.     

125I粒子植入或3DCRT联合TACE治疗晚期原发性肝癌患者临床疗效对比研究*

目的 研究¹²⁵I粒子植入或者三维适形放射治疗(3DCRT)联合肝动脉化疗栓塞(TACE)治疗肝细胞癌(HCC)患者的临床疗效。方法 采用随机数字表法将92例HCC患者分为观察组和对照组,每组46例。在观察组,采用¹²⁵I粒子植入联合TACE治疗,对照组患者接受3DCRT联合TACE治疗。检测血清甲胎蛋白(AFP)、甲胎蛋白异质体(AFP-L3)和高尔基体蛋白73(GP73)。结果 治疗后第4周时,观察组和对照组疾病控制率分别为62.5%和57.5%(P>0.05)],观察组和对照组1 a生存率分别为52.5%和45.0%(P>0.05)];治疗前和治疗后1月,两组血清AFP、AFP-L3和GP73水平比较,差异均无统计学意义(P>0.05);在治疗期间,两组白细胞降低、贫血、血小板降低和胃肠道反应发生率比较,差异均无统计学意义(P>0.05),观察组放射性肝损伤严重程度较对照组显著减轻,差异有统计学意义(P<0.05)。结论 采用TACE治疗晚期肝癌患者短期有效,与¹²⁵I粒子植入或3DCRT联合治疗可提高疗效,但联合¹²⁵I粒子植入可能副反应更轻。     

内镜超声引导下碘125粒子植入术治疗晚期食管癌患者吞咽困难初探

目的 评价内镜超声引导下碘125粒子植入术治疗晚期食管癌患者吞咽困难的安全性及有效性。方法 2017年12月—2018年11月,因晚期食管癌吞咽困难于解放军总医院接受内镜超声引导下碘125粒子植入术治疗的4例病例纳入回顾性分析,主要评价指标为治疗完成情况、并发症发生情况、治疗前后吞咽困难分级情况及内镜下癌灶大小变化情况、随访结果。结果 4例患者均成功完成内镜超声引导下碘125粒子植入术,未出现出血、胸痛、发热、咳嗽等并发症。治疗前吞咽困难分级Ⅱ～Ⅳ级,治疗后3个月降低至0～Ⅰ级,内镜下均可见癌灶有所缩小。随访12～23个月,3例生存,1例肿瘤晚期死亡。结论 内镜超声引导下碘125粒子植入术治疗晚期食管癌吞咽困难是一种安全有效的姑息治疗方法。     

Systematic review of novel ablative methods in locally advanced pancreatic cancer

Unresectable locally advanced pancreatic cancer with or without metastatic disease is associated with a very poor prognosis. Current standard therapy is limited to chemotherapy or chemoradiotherapy. Few regimens have been shown to have a substantial survival advantage and novel treatment strategies are urgently needed. Thermal and laser based ablative techniques are widely used in many solid organ malignancies. Initial studies in the pancreas were associated with significant morbidity and mortality, which limited widespread adoption. Modifications to the various applications, in particular combining the techniques with high quality imaging such as computed tomography and intraoperative or endoscopic ultrasound has enabled real time treatment monitoring and significant improvements in safety. We conducted a systematic review of the literature up to October 2013. Initial studies suggest that ablative therapies may confer an additional survival benefit over best supportive care but randomised studies are required to validate these findings.     

Stereotactic body radiotherapy (SBRT) for patients with locally advanced pancreatic cancer: A single center experience

IntroductionDespite advances in treatment, notably in systemic therapy, the prognosis of pancreatic adenocarcinoma (PADC) remains dismal. Stereotactic body radiotherapy (SBRT) is an emerging tool in the complex management of PADC. We review outcomes of SBRT for PADC at our institution.MethodsWe reviewed patients treated with SBRT for either unresectable PADC or locally recurrent PADC after surgery. Treatment was delivered using a robotic radiosurgery system with respiratory tracking. The median prescribed dose was 30 Gy (30–35 Gy), delivered in 5–6 fractions. Toxicities were reported as per CTCAE v4.0. Survival was estimated using the Kaplan–Meier method.ResultsBetween October 2010 and March 2016, 21 patients were treated at our institution. The median follow-up was 7 months (range: 1–28). The 1-year local control rate was 57%. The 1-year overall survival was 25% for locally advanced patients and 67% for those with local recurrences (p = 0.27). Eighty percent of cancer related deaths were due to metastatic progression. Five patients (24%) had Grade I–II gastrointestinal acute toxicity; one patient had fatal gastrointestinal bleeding 6 months after SBRT.ConclusionIn PADC, fractionated SBRT dose schedules near 30 Gy may strike the best balance of local control and bowel toxicity. More work is required to integrate pancreatic SBRT with modern systemic therapy.     

放射性~(125)I粒子治疗食管鳞癌的安全性及疗效

目的:探讨125I粒子在体内外对人ESCC的疗效和作用机制以及植入治疗胸段中晚期食管鳞癌(ESCC)的安全性及疗效.方法:细胞及动物实验:125I粒子植入体外培养的人食管鳞癌Eca-109细胞,分A组不加粒子(对照组);B组0.2mCi(低剂量组);C组0.4mCi(中剂量组);D组0.8mCi(高剂量组).分析细胞克隆形成率、细胞凋亡指数和细胞周期分布情况;建立裸鼠皮下移植性食管癌模型后,对照组(A组,不做任何处理)、假手术组(B组,穿刺瘤体1次,但不植入粒子)、低剂量组(C组,0.2mCi)、中剂量组(D组,0.4mCi)和高剂量组(E组,0.8mCi),计算各组抑瘤率.临床试验:前瞻性研究,入组时间为2000-2004年.根据ESCC术前CT分期标准,298例Ⅱ-Ⅲ期胸段ESCC患者随机分为术中联合125I粒子植入组及单纯手术组.依据TPS所确定的剂量,A组术中直视下植入125I粒子.选用0.5mCi的125I粒子20-40粒,总活度在10-30mCi,肿瘤匹配周边剂量60-70Gy,术后行粒子验证和质量评估.观察患者术后并发症、监测局部复发情况、评价患者疗效.结果:细胞克隆形成率B、C、D组均低于A组...     

内镜超声引导下125I粒子腹腔神经节植入术治疗晚期胰腺癌腹痛的初步研究

目的 评价内镜超声(EUS)引导下125I粒子腹腔神经节植入术治疗晚期胰腺癌患者腹痛的疗效以及其安全性.方法 对23例伴有中重度腹痛的晚期胰腺癌患者行EUS引导下125I粒子腹腔神经节植入术,术后每周随访1次,观察手术前后白细胞、血生化,患者的生存期、腹痛评分、麻醉药物的使用情况并记录手术相关的并发症.结果 所有患者均一次性手术成功,平均每例患者植入4枚粒子(2～6枚).术后有6例(26％)患者诉腹痛加重,但术后2周,患者的疼痛评分由平均6.09分降至4.48分(P＜0.05),所需要麻醉药物的剂量由术前71.74 mg迅速减少到55.22 mg(P＜0.05);未观察到并发症的发生.结论 EUS引导下125I粒子腹腔神经节植入术能有效缓解晚期胰腺癌患者的疼痛评分及麻醉药物的使用量.     

超声内镜引导下碘125粒子植入联合化疗治疗腹腔实体肿瘤的前瞻性研究

目的评价内镜超声检查术(EUS)引导下肿瘤内植入放射性碘125(~125 I)粒子联合化疗治疗胰腺癌的疗效和安全性,并探讨该方法用于其他腹腔原发或继发实体肿瘤治疗的可行性。方法对28例不能手术切除的腹腔实体肿瘤患者进行了EUS引导~(125)Ⅰ粒子植入内照射治疗,术后1周内采用吉西他滨 氟脲嘧啶化疗方案。包括中晚期胰腺癌25例(胰头癌8例、胰体尾癌17例),胆管癌腹膜后转移、腹膜后腺癌和贲门癌术后腹腔转移各1例。所有病例术前均参照TPS系统估算期望植入粒子数量,比较术前及术后不同时期的肿瘤直径、生活质量评分以及疼痛VAS评分等项目。结果 28例患者均经EUS成功植入~(125)Ⅰ粒子,平均每次植入粒子数量的中位数为10颗(5～20颗),最多1例胰腺癌分3次共植入30颗粒子,平均单颗粒子的放射性活度为26.2MBq。术后平均随访4.8个月(0.3～14个月),Kaplan-Meier法评估的中位生存期为9.4个月(95%CI6.5～11.6个月)。术后1个月评估疗效,达到部分缓解3例(10.7%),疾病稳定12例(42.9%),进展恶化10例(35.7%,其中8例死亡),3例失访。粒子植入1周后疼痛VAS评分由5.07±2.63下降至1.73±1.91(ρ<0.01),1个月后仍低于术前评分(3.53±1.51,ρ<0.05)。有52.9%的患者于术后24h内出现发热,无其他并发症出现。结论 EUS引导下~(125)Ⅰ粒子组织间植入是治疗包括胰腺癌在内的腹腔实体肿瘤的新型介入技术,可明显延缓肿瘤进展,具有稳定的止痛疗效,安全性高,值得进一步探讨其临床应用价值。     

125I粒子组织间植入治疗胰腺癌的实验研究

目的 探讨125I粒子组织间植入治疗胰腺癌的有效性.方法 Balb/c裸鼠腋下接种人胰腺癌SW1990细胞.按植入剂量不同将成瘤后裸鼠分为对照组和50 Gy、100 Gy、150 Gy、200 Gy组,每4 d测量肿瘤体积,21 d后处死裸鼠,称瘤重,计算肿瘤抑制率,常规病理检查,TUNEL法检测凋亡细胞.结果 对照组、50 Gy组、100 Gy组、150 Gy组及200 Gy组抑瘤率分别为0、(42.8±16.2)%、(55.1±22.3)%、(72.8±12.8)%及(75.6±8.6)%;以粒子为中心的肿瘤坏死面积分别为(6.3±2.1)%、(20.8±3.2)%、(36.3±3.1)%、(64.1±2.8)% 及(82.6±3.8)%;相对凋亡指数分别为1、2.07±0.57、2.75±0.33、4.64±0.45及7.04±0.34,各治疗组均显著高于对照组(P＜0.05).结论 125I粒子组织间植入可显著抑制肿瘤生长,放射粒子具有直接杀死肿瘤细胞和诱导凋亡双重作用.