循环肿瘤细胞监测在结直肠癌肝转移微波消融治疗中临床价值的评估

目的 探讨利用循环肿瘤细胞（CTCs）评估结直肠癌肝转移微波消融治疗的疗效及其与预后的关系。方法 收集2014年1月至2018年5月在南京市第二医院因结直肠癌肝转移行肝脏病灶微波消融治疗的29例患者的临床资料,并纳入术前与术后CTCs检测结果。计数资料分析采用χ2检验或Fisher确切概率法;生存分析采用Kaplan-Meier法和Log-rank检验。结果 经影像学评估,29例患者局部病灶微波消融的近期疗效为完全消融者8例、部分消融16例和进展5例。29例患者微波消融术后CTCs测量值较术前升高,差异有统计学意义（Z=-2.489,P=0.013）;患者的年龄、性别、术后CTCs升高与否、结直肠癌原发部位、同时性或异时性肝转移与微波消融近期疗效均无关（P＞0.05）。微波消融术后CTCs数目＜7个／ml患者局部肝转移病灶的近期疗效优于术后CTCs数目≥7个／ml者（P=0.031）。29例患者的中位生存时间（OS）为30.0个月（95％CI：10.7～49.3个月）。入组患者的年龄、结直肠癌原发部位及肝转移后的治疗方式与中位OS相关（P＜0.05）,而性别、同时性或异时性肝转移、术后CTCs升高与否及术后CTCs值／ml与中位OS均无关（P＞0.05）。结论 微波消融是结直肠癌肝转移局部治疗的有效手段,治疗前后CTCs数量的监测可能有助于评估其近期疗效。     

超声引导下射频消融治疗结直肠癌肝转移的疗效分析

【摘要】目的分析射频消融治疗对结直肠癌肝转移患者的疗效及安全性。方法回顾南京医科大学第一附属医院2017年1月至2020年1月期间接受肝转移灶射频消融治疗的49例结直肠癌患者临床资料，对射频消融前后肝转移灶大小变化、CT值以及血清肝功能指标、肿瘤标志物、淋巴细胞亚群水平的变化进行比较。结果射频消融术后2个月CT复查显示，肝转移灶长径之和虽有增加，但CT值明显下降（P＜001）；患者术后1个月复查血清丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、乳酸脱氢酶、癌胚抗原、甲胎蛋白、糖类抗原CA19 9水平，以及淋巴细胞亚群中的CD3+、CD8+、CD4+等指标与术前比较差异均无统计学意义（均P＞005）。结论射频消融术对结直肠癌肝转移患者疗效明确，可明显降低肿瘤密度，减小肿瘤活性，同时对肝功能无明显影响，是一种治疗结直肠癌肝转移的有效手段，具有较高的临床应用价值。     

结直肠癌切除同期射频消融肝转移的临床应用

肝脏是结直肠癌转移的最常见部位。有10％～25％的患者初次就诊或外科治疗时就发现肝转移，约20％的患者在结直肠癌手术后的一段时期发生肝转移。不经治疗的肝转移癌患者中位生存期仅5～9个月。因此，对肝转移癌的有效治疗十分重要。我们对13例结直肠癌肝转移患者实施结直肠癌切除同期肝转移灶射频消融治疗，总结报道如下。     

一期结直肠癌切除与射频消融治疗肝转移癌

目的:探讨一期结直肠癌切除与射频消融治疗肝转移癌的临床价值。方法:对5例术前确诊为结直肠癌,经CT和B超发现肝脏有转移病灶的患者,在行结直肠癌切除术后,同时在手术中一期完成B超或腹腔镜下多电极射频消融治疗肝转移癌。结果:5例患者随访3个月至29个月,其中1例病灶较大(直径6cm)者在术后 12个月死于肺转移及全身衰竭,另外4例术后已经分别生存3个月、6个月、22个月、25个月。结论:一期结直肠癌切除与射频消融治疗肝转移癌,具有疗效满意、方法安全、创伤小及痛苦小、避免二次剖腹手术等优点。     

一期结直肠癌切除与射频消融治疗肝转移癌

目的:探讨一期结直肠癌切除与射频消融治疗肝转移癌的临床价值.方法:对5例术前确诊为结直肠癌,经CT和B超发现肝脏有转移病灶的患者,在行结直肠癌切除术后,同时在手术中一期完成B超或腹腔镜下多电极射频消融治疗肝转移癌.结果:5例患者随访3个月至29个月,其中1例病灶较大(直径6cm)者在术后12个月死于肺转移及全身衰竭,另外4例术后已经分别生存3个月、6个月、22个月、25个月.结论:一期结直肠癌切除与射频消融治疗肝转移癌,具有疗效满意、方法安全、创伤小及痛苦小、避免二次剖腹手术等优点.     

结直肠癌肝转移的治疗进展

结直肠癌肝转移是影响结直肠癌预后的重要因素，治疗方案包括手术治疗、化疗（全身静脉化疗和介入治疗）、基因治疗和局部治疗（射频消融、激光消融、无水酒精注射和冷冻切除术）等，其中手术是目前唯一有效的治愈手段，手术死亡率1％～2．8％，术后5年生存率34％-38％，但仅有10％．25％结直肠癌肝转移患者确诊时适合于手术切除，因此各种非手术治疗的作用正日益受到关注。本文对结直肠癌肝转移的综合治疗作一综述。     

射频消融治疗结直肠癌肝转移

近十年来,射频消融在结直肠癌肝转移中的应用日渐增多,但尚未充分彰显其优势。全文就射频消融治疗结直肠癌肝转移的现状、存在的问题以及提升疗效的策略等问题作一探讨。     

结直肠癌肝转移治疗进展

结直肠癌肝转移是影响结直肠癌患者生存率的主要原因，目前对其治疗尚无最佳方案。肝叶切除术是治疗肝转移癌的“金标准”，对于3个以下的肝脏转移灶，行肝叶切除术是最佳选择。而对于无手术指征的肝转移患者，使用去氧氟尿苷的肝动脉化疗可获得较高的缓解率。随着生理周期化疗、基因治疗、射频消融治疗、肝血流阻断灌注治疗等方法的发展，结直肠癌肝转移患者的治愈率有望获得提高。     

结直肠癌肝转移治疗进展

结直肠癌肝转移是影响结直肠癌患者生存率的主要原因，目前对其治疗尚无最佳方案，肝叶切除术是治疗肝转移癌的“金标准”，对于3个以下的肝脏转移灶，行肝叶切除术是最佳选择。面对于无手术指征的肝转移患者，使用去氧氟尿苷的肝动脉化疗可获得较高的缓解率。随着生理周期化疗，其中治疗，射频消融治疗，肝血流阻断灌注治疗等方法的发展，结直肠癌肝转移患者的治愈率有望获得提高。     

腹腔镜下同期治疗结直肠癌并肝转移的临床观察

目的 探讨腹腔镜下行结直肠癌切除术同时处理合并肝转移癌的疗效。方法 对32例结直肠癌合并肝转移患者行腹腔镜下结直肠癌切除手术,同时利用腹腔镜直视下切除或射频消融等方法治疗肝转移癌。结果 32例患者手术过程顺利,手术时间为220～384min,平均280min,出血量为240～1300ml,无严重并发症发生。随访6～32月,18例存活,7例死于肺、脑或腹腔转移,3例死于复发,2例死于脑出血,2例死于心肌梗塞。结论 利用腹腔镜直视下治疗结直肠癌并肝转移安全有效,可避免二期手术的创伤。     

MR-guided laser-induced thermotherapy (LITT) of liver tumours: experimental and clinical data

MR-guided laser-induced interstitial thermotherapy (LITT) is a percutaneous, minimally invasive treatment modality for treating liver lesions/metastases, soft tissue tumours and musculoskeletal lesions. In this group, MR-guided LITT is currently performed under local anaesthesia on an out-patient basis with a specially designed saline-cooled laser application system. Nd:YAG laser (1064?nm wave length) was used for tumour ablation. Magnetic resonance imaging (MRI) using both open and closed MR units has proven clinically effective in validating the exact positioning of optical fibres. It also allows for real time-monitoring of thermal effects and the evaluation of treatment-induced coagulation necrosis. In liver tumours, percutaneous MR-guided LITT achieves a local tumour control rate of 98.7% at 3 months post-therapy and 97.3% at 6 months with metastases smaller than 5?cm in diameter. The mean survival rate for 1259 patients with 3440 metastases treated with 14 694 laser applications at the institute (calculated with the Kaplan-Meier method) was 4.4 years (95% confidence interval: 4.1–4.8?years) and median survival was 3.00 years. No statistically significant difference in survival rates was observed in patients with liver metastases from colorectal cancer vs metastases from other primary tumours. The rate of clinically relevant side effects and complications requiring secondary treatment was 2.2%. The clinical use of MR guided LITT (size<5?cm, number<5) is justified in patients with liver metastases of colorectal and/or breast cancers if the inclusion criteria are carefully observed. Further indications for MR guided LITT include recurrent cancer lesions in the head and neck, lung metastases and bone and soft tissue lesions.     

MR-guided laser-induced thermotherapy (LITT) of liver tumours: experimental and clinical data.

MR-guided laser-induced interstitial thermotherapy (LITT) is a percutaneous, minimally invasive treatment modality for treating liver lesions/metastases, soft tissue tumours and musculoskeletal lesions. In this group, MR-guided LITT is currently performed under local anaesthesia on an out-patient basis with a specially designed saline-cooled laser application system. Nd:YAG laser (1064 nm wave length) was used for tumour ablation. Magnetic resonance imaging (MRI) using both open and closed MR units has proven clinically effective in validating the exact positioning of optical fibres. It also allows for real time-monitoring of thermal effects and the evaluation of treatment-induced coagulation necrosis. In liver tumours, percutaneous MR-guided LITT achieves a local tumour control rate of 98.7% at 3 months post-therapy and 97.3% at 6 months with metastases smaller than 5 cm in diameter. The mean survival rate for 1259 patients with 3440 metastases treated with 14 694 laser applications at the institute (calculated with the Kaplan-Meier method) was 4.4 years (95% confidence interval: 4.1-4.8 years) and median survival was 3.00 years. No statistically significant difference in survival rates was observed in patients with liver metastases from colorectal cancer vs metastases from other primary tumours. The rate of clinically relevant side effects and complications requiring secondary treatment was 2.2%. The clinical use of MR guided LITT (size < 5 cm, number < 5) is justified in patients with liver metastases of colorectal and/or breast cancers if the inclusion criteria are carefully observed. Further indications for MR guided LITT include recurrent cancer lesions in the head and neck, lung metastases and bone and soft tissue lesions.     

Patterns of heat shock protein (HSP70) expression and Kupffer cell activity following thermal ablation of liver and colorectal liver metastases.

The time course and extent of thermal ablative injury differs in liver compared to tumour tissue. This may be influenced by differences in the expression of heat shock proteins (HSP) and the response of Kupffer cells to thermal injury. This study determines the expression and response of HSP70 and Kupffer cells to thermal ablative injury in a Murine model of colorectal liver metastases. Thermal ablation by laser (Nd-YAG wavelength 1064 nm) was induced in liver and colorectal cancer liver metastases in CBA strain mice. Laser energy was applied at 2 W for 50 s and produced incomplete tumour ablation. Established tissue injury was assessed in separate groups of animals at time points ranging from 12 h to 21 days following therapy. HSP70 and Kupffer cell expression at the margins of coagulated tissue was determined by immunohistochemical staining for HSP70 and F4/80 antigens, respectively. HSP70 was faintly expressed in the cytoplasm of all tumour cells, with distinct clusters exhibiting intense cytoplasmic and nuclear HSP70 staining (130+/-19 cells mm-2). Comparatively, HSP70 expression was uncommon in untreated control liver specimens (2+/-2 cells mm-2, p<0.001). Thermal ablation increased expression of HSP70 at coagulated tissue margins. The peak response in tumours occurred at 2 days post-ablation and was significantly greater than the peak response in liver, occurring at 12 h (809+/-80 cells mm-2 vs. 454+/-52 cells mm-2, p<0.001). HSP70 expression remained significantly elevated for 7 days following therapy in tumour tissue, compared to 3 days in liver. Kupffer cell numbers in untreated control tumours were significantly lower than in untreated control livers (285+/-23 cells mm-2 vs. 451+/-30 cells mm-2, p<0.001). Following thermal ablation, there was an initial decrease in Kupffer cell numbers at the margin of coagulation with subsequent persistent increases thereafter. In liver tissue, the peak Kupffer cell response occurred at 5 days post-therapy and was significantly greater than the peak response in tumour tissue 3 days post-thermal ablation (1074+/-34 cells mm-2 vs. 860+/-53 cells mm-2, p=0.007). Thermal ablation produces a greater and more prolonged HSP70 response in colorectal liver metastases than in liver tissue. It also induces persistent increases in Kupffer cell activity in liver and tumour tissue.     

超声新技术在结直肠癌肝转移诊疗中的应用进展

近年来超声造影、超声弹性成像、肝脏超声融合图像技术、腹腔镜超声等超声新技术逐渐成为结直肠癌肝转移诊断和治疗的重要工具。这些超声新技术的应用，提高了结直肠癌肝转移癌的检出率，帮助临床医师选择合理治疗方式从而延长患者生存时间。该文就超声新技术在结直肠癌肝转移诊断和治疗中的应用进展作一综述。     

结直肠癌肺转移的多学科综合诊疗现状

近年来,中国结直肠癌发病人数和死亡人数呈增长趋势,术后复发及转移是导致患者死亡的主要原因,肺是除肝以外结直肠癌转移最常见的好发部位。结直肠癌肺转移患者的治疗手段包括手术治疗、化疗、放疗、射频消融等多种方式。随着多学科诊疗的逐步发展和深入,结直肠癌肺转移患者的生存得到显著提高。     

Immediate evaluation and guidance of liver cancer thermal ablation by three-dimensional ultrasound/contrast-enhanced ultrasound fusion imaging

Purpose: To investigate the feasibility and value of three-dimensional ultrasound/contrast-enhanced ultrasound (3D US-CEUS) fusion imaging for the immediate evaluation of technical success and the guidance of supplementary ablation during the liver cancer thermal ablation procedure.

Materials and methods: Patients diagnosed with malignant liver cancer intending to receive thermal ablation including radiofrequency ablation (RFA) or microwave ablation (MWA) were enrolled. 3D US-CEUS fusion imaging was used to immediately assess the technical success and guide supplementary ablation. Contrast-enhanced computed tomography/magnetic resonance imaging (CECT/CEMRI) was performed one month after ablation to assess the technique effectiveness of the ablation. The registration success rate, duration time of 3D US-CEUS fusion imaging, technique effectiveness rate and major complications were recorded.

Results: In total, 76 patients with 95 tumours who underwent RFA or MWA and assessed by 3D US-CEUS fusion imaging were enrolled. The registration success rate of 3D US-CEUS fusion imaging was 93.7% (89/95), and the duration time was 4.0?±?1.1?min. Thirty lesions received supplementary ablation immediately during the procedure. The technique effectiveness rate of the ablation was 98.8% (81/82). There were no major complications related to ablation.

Conclusions: 3D US-CEUS fusion imaging is a feasible and valuable technique for the immediate evaluation and guidance of supplementary ablation during the liver cancer thermal ablation procedure.     

Interventionelle Therapie von Lungen- und Lebermetastasen

Objectives

To present interventional oncological therapy concepts for lung and liver metastases.

Material and methods

The different treatment techniques in interventional oncology are presented and include thermal ablation techniques, such as radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LITT), irreversible electroporation (IRE) and cryotherapy. Furthermore, vascular therapy methods are presented, such as transarterial chemoembolization (TACE), transarterial chemoperfusion (TACP), drug-eluting bead TACE (DEB-TACE), selective internal radiotherapy (SIRT), transpulmonary chemoembolization (TPCE) and chemosaturation.

Results

The interventional treatment techniques, such as RFA, MWA und LITT offer patients, especially those with nonresectable liver metastases from colorectal carcinoma, an effective therapy option if there are no more than 5 metastases ≤?3 cm in size. Further vascular treatment techniques for liver metastases are integrated in a multimodal approach. This is especially true for SIRT and TACE as a palliative therapy concept in chemotherapy-resistant intrahepatic metastases. For lung metastases the indications for thermal ablation are 3 lung metastases up to 3 cm in diameter per lobe. Here as well the patient is normally in a nonresectable situation and there is no response to systemic chemotherapy.

Discussion

Currently the multimodal approach in liver and lung metastases from colorectal carcinoma needs to be discussed also regarding interventional treatment options. These are either treatment techniques which are strictly localized to the tumor, such as thermal ablation or they are vascular treatment techniques which allow treatment of larger tumor areas or larger tumor volumes.     

基于分子成像的结直肠癌精准诊疗

分子成像是指借助分子成像探针,运用影像学技术反映活体状态下生物体内细胞及分子水平上特定分子的变化,并对其进行定性、定量、定时研究的无创手段。分子成像主要着眼于生物的变化过程,而不是这些变化导致的解剖变化、最终结果。由于分子成像具有上述特征,所以可以动态观察结直肠癌发生发展过程中的生物学行为,能很好克服直肠癌传统成像的不足。这不仅可以在分子水平对结直肠癌患者进行早期精准诊断,同时还有利于开展精准治疗和预后判断,从而有望改善结直肠癌患者的预后,最终提高患者的五年生存率。本文以基础研究及临床应用的需求为背景,对目前基于分子成像的结直肠癌精准诊疗的研究进展进行综述,以期为后续结直肠癌精准诊疗等方面的研究及应用提供思路方向和数据支撑。     

Surgical treatment of colorectal cancer metastasis

Colorectal cancer is one of the most common solid tumors affecting people around the world. A significant proportion of patients with colorectal cancer will develop or will present with liver metastases. In some of these patients, the liver is the only site of metastatic disease. Thus, surgical treatment approaches are an appropriate and important treatment option in patients with liver-only colorectal cancer metastases. Resection of colorectal cancer liver metastases can produce long-term survival in selected patients, but the efficacy of liver resection as a solitary treatment is limited by two factors. First, a minority of patients with liver metastases have resectable disease. Second, the majority of patients who undergo successful liver resection for colorectal cancer metastases develop recurrent disease in the liver, extrahepatic sites, or both. In this paper, in addition to the results of liver resection for colorectal cancer metastases, we will review the results of thermal ablation. Each of these surgical treatment modalities can produce long-term survival in a subset of patients with liver-only colorectal cancer metastases, whereas administration of systemic or regional chemotherapy rarely results in long-term survival in these patients. While surgical treatments provide the best chance for long-term survival or, in some cases, the best palliation in patients with colorectal cancer liver metastases, it is clear that further improvements in patient outcome will require multimodality therapy regimens. Modern surgical treatment of colorectal liver metastases can be performed safely with low mortality and transfusion rates, and surgical treatment should be considered in patients with disease confined to their liver.