Regular ArticleThe Operation and Efficacy of Cryosurgical, Nitrous Oxide-Driven Cryoprobe: I. Cryoprobe Physical Characteristics: Their Effects on Cell Cryodestruction
Abstract
For specification of the requirement for efficient cell cryodestruction in tumors, we tested a N2O-driven cryoprobe on experimental models. The cryoprobe was a 3-mm-diameter type for operation via fiber optic bronchoscopes in respiratory medicine. The freezing process, namely the "ice-ball" formation around the cryoprobe tip, was monitored with an impedancemeter. Physical characteristics and formation kinetics of the ice-ball formation (volume, diameter, freezing rate) were studied under defined experimental conditions in various biological liquids, including saline, serum, whole blood, and tumor cell suspensions (rat ascitic hepatoma), either plain or supplemented with gelling agents to approximate solid tumor consistency. Cell destruction (i.e., cryotoxicity to cells) within the ice ball produced in rat ascitic hepatoma was assessed in two ways: the cells, collected after ice ball thawing, were (1) seeded and cultured according to methods currently in use, or (2) injected into a rat to check for possible development of ascites. Both tests showed that cryotoxicity correlated with freezing rate within the ice ball, cell mortality was total next to the cryoprobe tip (i.e., site of highest freezing rate), while it was absent within the ice-ball periphery. In the area in between, mortality varied gradually. Together our experimental results show that cryotoxicity to cells may be improved by increasing the cell mortality (e.g., by brief precooling of the cryoprobe). Furthermore, for tumor cryosurgery, since cell mortality is maximal next to the cryoprobe, we point out that higher efficacy might be achieved by several overlapping short freezing spots in tumoral tissue, instead of one single prolonged freeze.
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2005, Seminars in Radiation OncologySurgical resection is often the first-line treatment option for primary and select metastatic hepatic malignancies. A minority of patients with hepatocellular carcinoma undergo potentially curative resection. Similarly, patients with liver-only metastasis are candidates for resection less than 15% of the time because of bilobar disease in which resection would sacrifice too great a volume of hepatic parenchyma, tumor proximity to major vascular or biliary structures thus preventing adequate margins, or unfavorable tumor biology. Ablative techniques directed at tumor elimination while minimizing injury to the surrounding functional hepatic parenchyma may be offered to select patients with unresectable cancers. Radiofrequency ablation, percutaneous ethanol injection, transarterial chemoembolization, cryoablation, microwave coagulation, and laser-induced interstitial thermotherapy all offer potential local tumor control and occasionally achieve long-term disease-free survival. This review focuses on the indications, anticipated benefits, and limitations of these ablative techniques.
In vivo cryochemotherapy of a human lung cancer model
2005, CryobiologyCryotherapy, an efficient technique to destroy tumour cells, is sometimes applied locally as a palliative treatment in lung cancers. It can be performed in combination with chemotherapy. Our aims were to determine in vivo: (1) the effects of cryochemotherapy in a human lung adenocarcinoma, (2) if it presents a benefit compared to the separate treatments and (3) if cryotherapy allows a tumour retention of the drug. Cells from the A549 cell line were xenografted into SCID mice. Tumours were treated by cryotherapy, chemotherapy (injection of Vinorelbine: Navelbine) or both and were studied morphologically at variable time points. Apoptosis was analysed by immunohistochemical staining of cleaved caspase-3 and by TUNEL. Intratumour Navelbine concentration was assessed by high performance liquid chromatography. Necrosis was important 2 h after cryochemotherapy (45% of the tumour surface) and at the later time points. Expression of cleaved caspase-3 was not significantly different from that of untreated tumours, except at the time point of 2 h where it was maximal (58%). Navelbine concentration was more important in tumours treated by chemotherapy than in tumours treated by cryochemotherapy, demonstrating that in our model, the benefit of the association observed 2 h after treatment was not due to a concentration-dependent effect.
Ablation techniques: Ethanol injection, cryoablation, and radiofrequency ablation
2002, Operative Techniques in General SurgeryAblative techniques for hepatocellular carcinoma
2001, Seminars in OncologyThe optimal management of hepatocellular carcinoma (HCC) is resection, but this is feasible in only a minority of patients for a variety of reasons, including metastatic disease, major vascular invasion, end-stage liver disease, and poor hepatic reserve. Inoperable patients may be candidates for ablative procedures that may eradicate tumor while minimizing the loss of functioning hepatic tissue that is inevitable with surgical resection. Percutaneous ethanol injection (PEI), hepatic arterial chemoembolization, cryoablation, radiofrequency ablation (RFA), and microwave coagulation offer the potential of local tumor control and sometimes achieve long-term disease-free survival. This review will discuss the indications, anticipated benefits, and limitations of current ablative techniques and place these procedures in proper perspective as options for patients with HCC.
Mechanisms of Tissue Injury in Cryosurgery
1998, CryobiologyAs the modern era of cryosurgery began in the mid 1960s, the basic features of cryosurgical technique were established as rapid freezing, slow thawing, and repetition of the freeze–thaw cycle. Since then, new applications of cryosurgery have caused numerous investigations on the mechanism of injury in cryosurgery with the intent to better define appropriate or optimal temperature–time dosimetry of the freeze–thaw cycles. A diversity of opinion has become evident on some aspects of technique, but the basic tenets of cryosurgery remain unchanged. All the parts of the freeze–thaw cycle can cause tissue injury. The cooling rate should be as fast as possible, but it is not as critical as other factors. The coldest tissue temperature is the prime factor in cell death and this should be −50°C in neoplastic tissue. The optimal duration of freezing is not known, but prolonged freezing increases tissue destruction. The thawing rate is a prime destructive factor and it should be as slow as possible. Repetition of the freeze–thaw cycle is well known to be an important factor in effective therapy. A prime need in cryosurgical research is related to the periphery of the cryosurgical lesion where some cells die and others live. Adjunctive therapy should influence the fate of cells in this region and increase the efficacy of cryosurgical techniques.
Bronchoscopic treatment of thoracic malignancy
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