Effective Hepatic Cryoablation: Does It Enhance Tumor Dissemination?

El-Shakhs, Soliman A; Shimi, Sami A.; Cuschieri, Alfred

doi:10.1007/pl00013192

Cited by 27 publications

(5 citation statements)

References 14 publications

(15 reference statements)

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“…On the one hand, cryoablation of a subcutaneous tumor retards the simultaneous growth of untreated tumor on the contralateral side and induces resistance to tumor rechallenge (Neel et al, 1970;Tanaka, 1982;Sabel et al, 2005;den Brok et al, 2006). On the other hand, cryoablation of the primary tumor alone is usually, but not always (El-Shakhs et al, 1999;Joosten et al, 2001), ineffective or deleterious in controlling the growth or spread of hematogenous metastases (Javadpour et al, 1979;Yamashita et al, 1982;Wing et al, 1988;Yan et al, 2006). Our studies confirm that cryoablation of local tumor as sole therapy is unable to retard the progression of metastatic cancer.…”

Section: Antimetastatic Effect Of Tumor Cryoablation 599mentioning

confidence: 99%

Cyclophosphamide Unmasks an Antimetastatic Effect of Local Tumor Cryoablation

Levy

Sidana

Chowdhury

et al. 2009

J Pharmacol Exp Ther

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Cryoablation of a solitary tumor mass releases intact tumor antigens and can induce protective antitumor immunity but has limited efficacy in the treatment of established metastatic cancer. Cyclophosphamide (Cy), an anticancer drug, selectively depletes regulatory T cells (T reg s) and attenuates suppression of antitumor immunity. We used a BALB/c mouse model of metastatic colon cancer to investigate the systemic antitumor effects of in situ cryotherapy alone or in combination with 200 mg/kg i.p. Cy. When combined with Cy, cryoablation was significantly more effective than either surgical excision or cautery at inducing systemic antitumor immunity, resulting in the cure of a fraction of animals with established metastatic disease and resistance to tumor rechallenge. Lymphocytes from cured animals contained an expanded population of tumor-specific, interferon-␥ producing T cells and transferred antitumor immunity to naive recipients. Depletion of CD8 ϩ cells significantly impaired the adoptive transfer of antitumor immunity. Furthermore, treatment with Cy and cryoablation was associated with a significant decrease in the ratio of regulatory to effector CD4 ϩ

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Section: Antimetastatic Effect Of Tumor Cryoablation 599mentioning

confidence: 99%

Cyclophosphamide Unmasks an Antimetastatic Effect of Local Tumor Cryoablation

Levy

Sidana

Chowdhury

et al. 2009

J Pharmacol Exp Ther

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“…16,19,27 In vitro studies have identified −20°C as the minimal lethal temperature for colorectal cancer 31,32 ; −25°C for renal cancer, 29,33 pancreatic cancer, 34,35 and bladder cancer 36,37 ; and −35° for liver cancer. 24,28,38 Other studies have demonstrated that the application of a repeat or double freeze procedure can elevate the minimal lethal temperature for a given cancer type. For instance, Santucci et al 36 reported a repeat freeze can elevate the lethal temperature in bladder cancer to −20°C.…”

mentioning

confidence: 99%

Breast Cancer Cryoablation: Assessment of the Impact of Fundamental Procedural Variables in an In Vitro Human Breast Cancer Model

Snyder

Buskirk

Baust

et al. 2020

Breast Cancer�(Auckl)

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Introduction: Breast cancer is the most prominent form of cancer and the second leading cause of death in women behind lung cancer. The primary modes of treatment today include surgical excision (lumpectomy, mastectomy), radiation, chemoablation, anti-HER2/neu therapy, and/or hormone therapy. The severe side effects associated with these therapies suggest a minimally invasive therapy with fewer quality of life issues would be advantageous for treatment of this pervasive disease. Cryoablation has been used in the treatment of other cancers, including prostate, skin, and cervical, for decades and has been shown to be a successful minimally invasive therapeutic option. To this end, the use of cryotherapy for the treatment of breast cancer has increased over the last several years. Although successful, one of the challenges in cryoablation is management of cancer destruction in the periphery of the ice ball as the tissue within this outer margin may not experience ablative temperatures. In breast cancer, this is of concern due to the lobular nature of the tumors. As such, in this study, we investigated the level of cell death at various temperatures associated with the margin of a cryogenic lesion as well as the impact of repetitive freezing and thawing methods on overall efficacy. Methods: Human breast cancer cells, MCF-7, were exposed to temperatures of −5°C, −10°C, −15°C, −20°C, or −25°C for 5-minute freeze intervals in a single or repeat freeze-thaw cycle. Samples were thawed with either passive or active warming for 5 or 10 minutes. Samples were assessed at 1, 2, and 3 days post-freeze to assess cell survival and recovery. In addition, the modes of cell death associated with freezing were assessed over the initial 24-hour post-thaw recovery period. Results: Exposure of MCF-7 cells to −5°C and −10°C resulted in minimal cell death regardless of the freeze/thaw conditions. Freezing to a temperature of −25°C resulted in complete cell death 1 day post-thaw with no cell recovery in all freeze/thaw scenarios evaluated. Exposure to a single freeze event resulted in a gradual increase in cell death at −15°C and −20°C. Application of a repeat freeze-thaw cycle (dual 5-minute freeze) resulted in an increase in cell death with complete destruction at −20°C and near complete death at −15°C (day 1 survival: single −15°C freeze/thaw = 20%; repeated −15°C freeze/thaw = 4%). Analysis of thaw interval time (5 vs 10 minute) demonstrated that the shorter 5-minute thaw interval between freezes resulted in increased cell destruction. Furthermore, investigation of thaw rate (active vs passive thawing) demonstrated that active thawing resulted in increased cell survival thereby less effective ablation compared with passive thawing (eg, −15°C 5/10/5 procedure survival, passive thaw: 4% vs active thaw: 29%). Conclusions: In summary, these in vitro findings suggest that freezing to temperatures of 25°C results in a high degree of breast cancer cell destruction. Furthermore, the data demonstrate that the application of a repeat freeze procedure with a passive 5-minute or 10-minute thaw interval between freeze cycles increases the minimal lethal temperature to the −15°C to −20°C range. The data also demonstrate that the use of an active thawing procedure between freezes reduces ablation efficacy at temperatures associated with the iceball periphery. These findings may be important to improving future clinical applications of cryoablation for the treatment of breast cancer.

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“…El‐Shakhs et al . 36 also failed to demonstrate that hepatic cryotherapy enhances tumour dissemination in a rat model. The different findings might be related to the difference in their study designs.…”

Section: Discussionmentioning

confidence: 98%