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International Journal of Modern Cancer Therapy (2000) Vol.3 No.1
The Treatment of Irresectable Liver Tumors by
Percutaneous Targeted Ar-He Cryoablation
Senming Wang, Jiren Zhang, Qiuping Peng, Yan Zhao, Guoqang Chen, Hongqing Wu
Oncology Center, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China

ABSTRACT The aim of this investigation was to evaluate the results and safety of percutaneous targeted Ar-He (argon-helium) cryoablation in irresectable malignant Liver tumors. Between Oct 1999 and Feb 2000, 30 patients with irresectable hepatocellular carcinoma (13 patients) and irresectable metastases form colorectal cancer (17 patients) were selected to be treated with CRYOcare surgical system. Double freeze-thaw cycles were performed with 15-20 minutes freezing. Follow-up monitoring was performed at 1 week, 1 month and then every 3 months after cryoablation. There were no intraoperative or postoperative complications. The first CT study suggested complete destruction of all liver tumors smaller than 3 cm, and no local recurrence within a follow-up interval. The tumors with a diameter of more than 3cm were 90 percent destroyed. The serum levels of AFP or CEA decreased within various extents and half of them returned to normal over a period of 1 month to 3 months. The postoperative CD3+, CD4+, CD8+ T lymphocytic subsets, CD3--/CD56+/CD16+ NK cell of the peripheral blood had been found to be increased significantly (p<0`05). We concluded that Percutaneous targeted Ar-He cryoablation in treatment of the patients with irresectable liver tumors is an advantageous, effective and safe cryotherapy. The CRYOcare surgical system is the powerful and easy to be useful cryosurgery system.

KEYWORDS cryotherapy, Percutaneous cryoablation, liver tumors.
Cryoablation of liver tumors is more used in oncological clinical when hepatic resection cannot be performed, or clearance is restricted by anatomical limitation. Advances in the technology of cryomachines and the experience gained in the open cryoablation of liver tumors have allowed todevelop a new percutaneous targeted Ar-He (argon-helium) cryoablation for treatment of the patients with irresectable liver tumor. The aim of this investigation was to evaluate the results and safety of this new cryotherapy.

PATIENTS AND METHODS
Between Oct 1999 and Feb 2000, 30 patients with irresectable malignancy liver tumors were selected for percutaneous targeted Ar-He cryoablation, including 13 patients with hepatocellular carcinoma (HCC) and 17 patients with colorectal liver metastases. Only patients with liver tumors that could be visualized clearly by ultrasonography were included .The median age of these patients was 55 (range 30-65) years and 18 were men .The mean diameter of liver tumors was 4.7 (range 2-10) cm.
Cryoablation was performed with CRYOcare surgical system (Endocare corporation, USA). The CRYOcare system provided various ultrasound-guided probes(2, 3, 5, 8mm diameter) and continuous temperature monitoring of targeted tissue. Ultrasonography (US) or computed tomograpy(CT) were used to target the lesion, and to monitor iceball during the percutaneous targeted Ar-He cryoablation.
Under local anesthesia, the cryoprobe was inserted into tumor with US or CT guidance. Liquid argon was delivered to the tip of probe and the temperature of the targeted lesion reached -150℃ within 10 second. The formation of an iceball had to exceed the tumor margin by 1 cm, achieving a temperature of -40℃ at the tumor edge. The temperature in target tissue was increased to be 20-40℃ by delivering liquid helium to frozen zone for 5 minutes. Then the second freeze-thaw cycle was performed.

Patients were kept in hospital for at least 2 days after percutaneous targeted Ar-He (argon-helium) cryoablation. Follow-up monitoring consisted of CT, US and determination of AFP or CEA at 1 week, 1 month and then every 3 months after cryoablation, also the CD3+, CD4+, CD8+ T lymphocytic subsets, CD3--/CD56+/CD16+ NK cell of the peripheral blood were evaluated with the flow cytometry.

RESULTS
The probes of 2, 3, 5 mm produced iceballs of 2.5×4.5, 3.5×6, 6×7 cm respectively after 15-20 minutes freezing. Lesion was surrounded by the low-density iceball (Fig 1). The contrast enhanced CT demonstrated there was low-density lesion in the central portion of the cryolesion at 1 week later (Fig 2). The first CT study suggusted complete destruction of all liver tumors smaller than 3cm (n=11) and no local recurrence within a follow-up interval (range 1-3 months). The tumors with diameter of more than 3cm (n=19) were 90 percent destroyed. Pathologic specimen 1-week post freezes showed necrosis of the frozen tumor tissue(Fig 3).
Fig1(preoperative US) Fig1(postoperative US) Fig2(preoperative CT) Fig2(preoperative CT)

The postoperative CD3+, CD4+, CD8+ T lymphocytic subsets, CD3--/CD56+/CD16+ NK cell of the peripheral blood increased significantly (p<0`05).
There were no intraoperative or postoperative complication, such as cracking of the lesions, bile fistula, bleeding. All patients recovered quickly. The mean hospital stay after the procedure was 2 (range 1-4) days.

Table. The level of T lymphocyte and NK cell (x±s,%)

  CD3+ CD4+ CD8+ NK cell
Pretreatment 58.56±5.67 22.21±6.99 32.11±6.02 10.75±4.57
Postoperative (1 week) 65.73±8.75 27.15±7.01 35.75±7.16 13.87±5.30
P value p<0`01 p<0`01 p<0`05 p<0`05

CONCLUSIONS

Cryoablation is now a widely accepted modality for dealing with irresectable liver tumors, in particular for patients with lesion in multiple lobes, tumors in locations that are difficult to resect and for patients with limited hepatic functional reserve [1]. Cryoablation may increase the number of patients with irresectable liver tumors. Rather than an alterative to resection, cryoablation is to be regarded as a complement to hepatectomy and as an additional means to achieve tumor eradication [2]. Cryoablation may achieve complete tumor destruction by very low temperature and increase immune function after procedure. Cryosurgery is mainly employed via laparotomy. Some study suggests that percutaneous cryoablation is an effective alterative to open cryoablation [3,4]. In the initial experience with percutaneous cryoablation, suitable lesions were selected, namely solitary tumors that were readily accessible with a percutaneous probe and easily visible on ultrasonography before and during the procedure.

In our study, Endocare`s CRYOcare surgical system, a new argon-based CRYOcare system can create an iceball faster with steeper internal temperature gradients than liquid nitrogen-based cryomachines [5]. Furthermore, helium gas rapidly can increase the temperature of frozen tissue, which led to further tumor destruction. Liver tumors smaller than 3 cm were completely destroyed and others were 90 percent destroyed. The level of T lymphocyte and NK cell of the peripheral blood increased after the procedure, which suggests immune function of the patients were enhanced. With ultrasound-guided probes and continuous temperature monitoring of targeted tissue, the CRYOcare system provides the highest levels of precision and control to avoid damage to surrounding tissue. There were no introperative or postoperative complication. The CRYOcare system is small and easy to use. The technical feasibility of the procedure (i.e. reaching the lesion and monitoring the iceball by US) was no more difficult than with open cryoablation.

Acknowledging that the number of patients was small and the length of follow-up was short, the series suggests that percutaneous targeted Ar-He cryoablation in irresectable liver tumors is an advantageous, effective and safe alternative to open cryoablation and the CRYOcare surgical system is the powerful and easy to use cryosurgery system available.

REFERENCES
1. Parker SL, Tong T, and Bolden, et al. Cancer statistics 1997.CA Cancer J Clin 1997; 47: 5-27.

2. Adam R, Akpinar E, Johann M, et al. Place of cryosurgery in the treatment of malignant liver tumors. Ann Surg 1997; 225: 39-50.

3. Schurder G, Pistorius G, Schneider G, et al. Preliminary experience with percutaneous cryotherapy of liver tumors. Br J Surg 1998; 85: 1210-1211.

4. Adam R, Majno P, Castaing D, et al. Treatment of irresectable liver tumors by percutaneous cryosurgery. Br J Surg 1998; 85: 1493-1494.

5. Rewcastle JC, Sandison GA,Saliken JC, et al . Considerations during clinical operation of two commercially availabe cryomachines..J Surg Oncol 1999; 71:106-111.

简介

  前列腺癌是男性癌患者死亡的第二大杀手。对于尚未扩散的前列腺癌,传统疗法包括手术切除前列腺和放射线疗法。但是这些疗法常常引起严重的并发症。

  手术切除后的病理切片常常显示癌细胞已经扩散到前列腺以外,手术并未将癌细胞全部清理干净。据报道,前列腺切除手术的失败率为50-60%,失败的原因往往是医生们低估了癌 症的扩散范围。
放射线疗法的失败率为50-80%。由于传统疗法的种种局限,医学界正在努力寻求更有效和更少侵犯病人身体的疗法。其中日趋崭露头角的超低温疗法显示了巨大的潜力。 历史回顾

  超低温治疗前列腺癌是将前列腺冷冻,将其中的癌细胞和前列腺细胞同时摧毁。1968年,超低温首次用于前列腺癌的治疗,达到了摧毁细胞组织的目的。70年代,伯尼医生报告了他使用超低温治疗前列腺癌的经验。他的报告显示:在癌症的每一阶段,经超低温治疗的病人的长期存活率与接受手术切除的病人是同样的。
  
  但是,由于当时缺乏能够精确监测冷冻过程的精密仪器,造成很多并发症,这项技术被迫停止使用。1988年,同步超声波首次应用于监测冷冻过程。1994年,有两位医生报告了一项大为改进的超低温手术技术。这项技术综合采用先进的能透视直肠的超声波。先进的超低温技术和大大改进的放射线技术。 超低温根除前列腺癌

  手术前准备:准备接受超低温治疗的病人要先接受超声波透视和前列腺病理检查,以便为医生提供准确位置与大小,周围神经组织等情况。这些资料对手术成功与否起着决定性作用。

  为了高度准确地探明癌症现状,医生必须使用先进的彩色超声波仪器。病人还要接受骨质扫描和骨盆的CT扫描,以便确定癌症没有扩散。必要时,病人还要做淋巴结检查。如果发现癌症已经转移,病人不宜做超低温手术。
手术前用药:病人在手术前接受3-6个月的减少雄性激素治疗。雄性激素的减少能缩小前列腺和癌细胞组织面积。
超低温手术:手术前一天,病人要做例行的血液检查和X光透视。医疗小组包括一个有执照的放射科医生和泌尿科医生。为了保护尿道,医生们需要放置一个尿道保温装置(一根放在尿道的导管,内有不断循环的摄氏40度生理盐水)。因为在手术过程中,有时前列腺的尿道壁也会被冻伤,坏死的细胞组织会掉入膀胱和膀胱颈,造成手术后排尿困难。使用尿道保温装置可大大减轻这种症状。

   超低温手术使用一般麻醉或者脊椎麻醉。医生们把5-8把针从直肠与阴囊之间的皮肤表层刺入会阴部,在超声波的引导下逐渐把针推进到事先选好的前列腺位置上,冷冻用的低温探针再通过扩大了的针道插入。前列腺周围的关键部位放置数个温差电偶,用来观测温度变化。

  制冷开始了。冷媒通过特殊设计的空心低温探针(直径3毫米和8毫米)输入。随着温度的下降,探针顶端会形成一个冰球,医生们通过超声波屏幕仔细观察冰球的大小的形状。8 毫米的探针顶端在三分钟内达到摄氏零下195度,3毫米的探针顶端温度达到摄氏零下175度后,在20分钟内形成一个直径5厘米的冰球。 温度越低,结冰速度越快,冰球体积越大。

 

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