1. Death of Cell and Tissue in Cryosurgery
Dr. Sajio Sumida Clinic
This paper describes the three mechanisms of cryo-destruction of cells and tissues (referred to as the ‘target’) in cryosurgery. These mechanisms include 1) mechanical and osmotic destruction of the target cells, 2) cryo-necrosis due to microcirculatory failure combined with inflammation and 3) cryo-immune responses.
There are a host of variables that are involved in the causes of cryo-destruction of the target. They include: sizes of cryoprobes, the kinds of refrigerant, the method of generation of low temperature, the cooling and warming rate, the general condition of patients, the location and size of target, and the strength of immune responses. The author describes these mechanisms conceptually because it is so difficult to strictly designate any one individual variable.
Cryosurgery takes a relatively longer time for complete wound-healing of the cryo-destructed target in contrast to surgical ablation intervention of the target by conventional resection. However, the author emphasizes that cryosurgery has some unique advantages that cannot be left unmentioned, namely, it is the treatment of choice for unresectable tumors located on the face, vulva, and porta hepatis.
- Cell death at low temperature
- Intracellular ice formation
2. Image-Guided Cryoablation
Department of Biomedical Science and Engineering, Faculty of Health Sciences, Hokkaido University
Image-guided thermal ablation has become a popular category of interventional radiology. Radiofrequency ablation, laser interstitial thermal ablation, high-intensity focused ultrasound, microwave coagulation and cryoablation are included in this category. An image-guided technique for cryoablation was developed at the end of this last century. We are able to choose ultrasonography (US), computed tomography (CT) or magnetic resonance imaging (MRI) for targeting tumors and monitoring the freezing process. Each imaging modality has its own characteristics. US is widely employed for targeting many kinds of lesion because of its high temporal resolution. However, only the near surface of the iceball is delineated on the ultrasonogram. CT-guidance is available for targeting and monitoring cryoablation of lung and bone tumors. The ablation zone is of high density in the lung. On the other hand, the frozen area is visible as a low density area in other organs. MR imaging provides a very high contrast between frozen and non-frozen tissue, and multiple slice and multidirectional images are useful for observing the shape of the frozen area and its spatial relation to adjacent tissue. Real time thermal mapping of the frozen tissue and tumor visualization in the ablation zone are necessary for safer and more accurate cryoablation.
3. Cryosurgery for Breast Disease
Kameda Medical Center, Breast Center
Eisuke Fukuma, Shinji Ozaki, Mitsuhiro Tozaki, Naomi Sakamoto
Satoko Abe, Terumasa Kurihara, Takako Suzuki, Michiko Sagawa
Since 2006 we have applied cryosurgery for various breast diseases including small breast cancer, fibroadenoma, and advanced breast cancer to enhance immunity.
Eight patients with small breast cancer (mean size 7.6㎜) had non-surgical cryoablation, and a short follow up failed to reveal any local recurrence at the ablated sites. Four patients had cryoablation for fibroadenoma and have never experienced recurrent tumor. Although cryosurgery for breast disease has potential for development, we have to accumulate further cases and evaluate pathological lesions taken from post-ablated lesions.
- Small breast cancer
- Cryo-assisted lumpectomy
4. Percutaneous Cryoablation for Pulmonary Malignancies
Department of Diagnostic Radiology and Department of Thoracic Surgery1）, School of Medicine, Keio University
Seishi Nakatsuka, Hideki Yashiro, Masanori Inoue
Masafumi Kawamura1), Yotaro Izumi1), Sachio Kuribayashi
Our experience of percutaneous cryoablation for pulmonary malignancies (PCP) under CT fluoroscopic guidance and the difference from RF ablation will be mentioned.
All procedures were percutaneously performed under local anesthesia with a multi-detector row CT scanner using multi-slice CT fluoroscopy. A coaxial technique using a 21-gauge fine needle and an 8 to 11-gauge coaxial needle was applied to penetrate a tumor. Tumors were frozen into iceballs using high-pressure argon and Joule-Thomson effect.
More than 100 patients with more than 200 primary or secondary pulmonary malignant tumors underwent percutaneous cryoablation. The procedure was well tolerated by all patients. One- and two-year local control rates were about 80％ and 70％, respectively. Complications included pneumothorax, pleural effusion and hemothorax. The rate of chest tube insertion stayed around 10％.
The biggest difference from RFA is painlessness in PCP sessions. In addition, multiple cryoprobe activation is possible in PCP and the difficulty of the PCP procedure should be mentioned. Our experience confirms the feasibility, safety and efficacy of PCP.
- Lung cancer
- Metastatic lung tumor
- CT fluoroscopy
5. Intratumoral Administration of BCG-CWS Treated DC Following Tumor Cryoablation
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine
Based on the analysis of immune responses to human cancer, we have developed immuno-therapy combined with tumor cryoablation. In murine bilateral tumor models, intratumoral administration of BCG-CWS treated dendritic cells following tumor cryoablation resulted in inhibition of remote untreated large tumors. The enhanced uptake of tumor antigens by the injected DC through tumor cell necrosis and apoptosis induced by cryoablation, and the DC stimulation with TLR stimulating BCG-CWS, enhanced induction of anti-tumor CD8＋ CTL through efficient antigen spreading, and induced tumor regression. Based on the mouse study, clinical trials of this protocol were performed for patients with melanoma, primary lung cancer, and liver metastasis of colon cancers. In some patients, SD with decreased tumor markers was obtained along with induction of systemic immune responses. Improved protocols are currently designed for more effective immunotherapy with cryoablative tumor treatment.
- Dendritic cells