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Wu D, Liao X, Gao J, Wang K, Xu W, Wang F, Jin Z, Wu D, Li Q, Gao W. A novel technique of cryodenervation for murine vagus nerve: implications for acute lung inflammation. Respir Res 2025; 26:15. [PMID: 39806332 PMCID: PMC11730848 DOI: 10.1186/s12931-025-03108-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 01/08/2025] [Indexed: 01/16/2025] Open
Abstract
BACKGROUND Neuroimmune interaction is an underestimated mechanism for lung diseases, and cryoablation is a competitive advantageous technique than other non-pharmacologic interventions for peripheral nerve innervating the lung. However, a lack of cryodenervation model in laboratory rodents leads to the obscure mechanisms for techniques used in clinic. METHOD Herein, we developed a novel practical method for mouse peripheral nerve cryoablation, named visualized and simple cryodenervation (VSCD). We first estimated the feasibility, safety and effectiveness of the technique via haematoxylin-eosin staining, histochemistry or immunofluorescence staining and immunoblotting assay. We then constructed the acute lung injury (ALI) model triggered by lipopolysaccharide (LPS) to verify the effect of VSCD in the resolution of pulmonary inflammation. Besides, the IL-10 knockout mice were also applied to explain the underlying mechanism of the protective activity of VSCD in ALI mice. RESULT We demonstrated that VSCD was able to induce a reliable and stable blockade of innervation, but reversible structural damage of mouse vagus nerve without detectable toxicity to lung tissues. Cholinergic parasympathetic nerve in the mouse lung coming from vagus nerve was activated at the initial stage (1 week) after VSCD, and blocked 3 weeks later. By use of the ALI mouse model, we found that VSCD effectively decreased pulmonary inflammation and tissue damage in the ALI mice. Moreover, the activated cholinergic anti-inflammatory pathway (CAP) and elevated IL-10 expression might explain the protective action of VSCD following LPS challenge. CONCLUSION This study fills the gap in the cryoablation for mouse vagus nerve, thereby guiding the application of cryodenervation in clinical management of pulmonary diseases. It also offers evidence of anti-inflammatory potential of VSCD in ALI mouse model and opens therapeutic avenues for the intervention of acute lung inflammation.
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Affiliation(s)
- Di Wu
- Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China
| | - Ximing Liao
- Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China
| | - Jing Gao
- Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China
| | - Kun Wang
- Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China
| | - Wujian Xu
- Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China
| | - Feilong Wang
- Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China
| | - Zhixian Jin
- Department of Pulmonary and Critical Care Medicine, Affiliated Calmette Hospital of Kunming Medical University and The First People's Hospital of Kunming City, Yunnan, 650224, China
| | - Dandan Wu
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nantong University, Nantong, 226001, China.
| | - Qiang Li
- Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
| | - Wei Gao
- Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
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Christensen RL, Son HG, Zhou EY, Olesen UH, Garibyan L, Farinelli WA, Sakamoto FH, Rox Anderson R, Haedersdal M, Demehri S. Cutaneous Immune Responses to Ablative Fractional Laser, Heat- and Cold-Based Dermatological Procedures. Lasers Surg Med 2025; 57:101-111. [PMID: 39698750 DOI: 10.1002/lsm.23868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 10/24/2024] [Accepted: 11/29/2024] [Indexed: 12/20/2024]
Abstract
OBJECTIVE Physical treatment modalities, such as ablative fractional laser (AFL), electrocautery, and cryotherapy, are extensively used in the field of dermatology. This study aimed to characterize the short-term innate and adaptive immune responses induced by AFL compared with heat- and cold-based procedures. MATERIALS AND METHODS Innate (CD11b+Ly6G+ neutrophils) and adaptive (CD8+CD3+ T cells) immune cell infiltration and histopathological changes were examined in murine skin on Days 1 and 7, following AFL, monopolar-electrocautery (RF), thermocautery, and cryotherapy. Interventions were standardized to reach the reticular dermis. Clinical skin reactions were photo-documented daily. As a comparator, the adaptive immune response was examined in murine basal cell carcinomas (BCC) on Day 7 after AFL exposure. RESULTS Baseline histopathology confirmed immediate deep dermal tissue impact by all procedures. Immune cell dynamics varied across treatments throughout the progression of clinical and histopathological responses. On Day 1, AFL and heat-based procedures triggered an innate immune response, characterized by CD11b+Ly6G+ neutrophil cell infiltration that correlated with histopathological findings and immediate onset of clinical skin reactions. In addition, heat-based procedures led to an increase in overall dermal CD45+ cells (Day 1), which continued to rise for AFL and RF-electrocautery at Day 7 posttreatment. On the contrary, cryotherapy did not induce immediate (Day 1) innate immune responses, but instead a delayed increase in neutrophil and CD45+ cell infiltration (Day 7), which coincided with the late onset of clinical reaction. CD3+ T cells and CD8+CD3+ T cells demonstrated a similar pattern, with an increase observed for heat-based procedures on Day 1 and a delayed increase for cryotherapy on Day 7. Distinctive for AFL-treated skin, the level of dermal CD3+ T cells increased over time, significant by Day 7, and AFL-treated mouse BCCs responded with increased CD8+ T cell infiltration at Day 7 posttreatment. CONCLUSION Heat- and cold-based procedures developed distinct cutaneous immune responses, with cryotherapy resulting in a delayed response compared to immediate immune responses from heat-based procedures. The substantial T cell response induced by AFL in the skin and BCC tumors indicates a potential for AFL as an adjuvant in immunotherapeutic treatments of keratinocyte cancers.
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Affiliation(s)
- Rikke L Christensen
- Center for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Department of Dermatology and Venereology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Heehwa G Son
- Center for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Eray Yihui Zhou
- Center for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Uffe H Olesen
- Department of Dermatology and Venereology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Lilit Garibyan
- Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - William A Farinelli
- Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Fernanda H Sakamoto
- Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - R Rox Anderson
- Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Merete Haedersdal
- Department of Dermatology and Venereology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
- Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Shadmehr Demehri
- Center for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
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Falk KL, Laeseke PF, Kisting MA, Zlevor AM, Knott EA, Smolock AR, Bradley C, Vlaisavljevich E, Lee FT, Ziemlewicz TJ. Clinical translation of abdominal histotripsy: a review of preclinical studies in large animal models. Int J Hyperthermia 2023; 40:2272065. [PMID: 37875279 PMCID: PMC10629829 DOI: 10.1080/02656736.2023.2272065] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 10/12/2023] [Indexed: 10/26/2023] Open
Abstract
Histotripsy is an emerging noninvasive, non-thermal, and non-ionizing focused ultrasound (US) therapy that can be used to destroy targeted tissue. Histotripsy has evolved from early laboratory prototypes to clinical systems which have been comprehensively evaluated in the preclinical environment to ensure safe translation to human use. This review summarizes the observations and results from preclinical histotripsy studies in the liver, kidney, and pancreas. Key findings from these studies include the ability to make a clinically relevant treatment zone in each organ with maintained collagenous architecture, potentially allowing treatments in areas not currently amenable to thermal ablation. Treatments across organ capsules have proven safe, including in anticoagulated models which may expand patients eligible for treatment or eliminate the risk associated with taking patients off anti-coagulation. Treatment zones are well-defined with imaging and rapidly resorb, which may allow improved evaluation of treatment zones for residual or recurrent tumor. Understanding the effects of histotripsy in animal models will help inform physicians adopting histotripsy for human clinical use.
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Affiliation(s)
- Katrina L Falk
- Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, USA
- Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA
| | - Paul F Laeseke
- Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, USA
- Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA
| | - Meridith A Kisting
- Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA
| | - Annie M Zlevor
- Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA
| | - Emily A Knott
- Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, USA
| | - Amanda R Smolock
- Department of Radiology, Division of Interventional Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Charles Bradley
- School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Eli Vlaisavljevich
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Fred T Lee
- Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, USA
- Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA
- Department of Urology, University of Wisconsin, Madison, Wisconsin, USA
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McDaniel A, Freimark B, Navarro C, Von Rothstein K, Gonzalez D, Linder K, Nuccitelli R. Nano-pulse stimulation™ therapy (NPS™) is superior to cryoablation in clearing murine melanoma tumors. Front Oncol 2023; 12:948472. [PMID: 36844920 PMCID: PMC9945337 DOI: 10.3389/fonc.2022.948472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 12/30/2022] [Indexed: 02/11/2023] Open
Abstract
Background Nano-Pulse Stimulation™ Therapy (NPS™) is a new, bioelectric modality that applies ultrashort pulses of electric energy to trigger regulated cell death in treated tissues. Instead of initiating necrosis by heating or freezing, NPS therapy permeabilizes intracellular organelles to activate the cell's own self-destruct pathway of programmed or regulated cell death. Unlike cryotherapies that can both damage structural tissues and diffuse into the periphery beyond the margins of the lesion, NPS only affects cells within the treated zone leaving surrounding tissue and acellular components unaffected. Methods We generated melanoma tumors in mice by injecting B16-F10 cells intradermally and compared the efficacy and resulting skin damage from Nano-Pulse Stimulation Therapy with that of cryoablation in clearing these tumors. Results The results of the study demonstrate that NPS is superior at clearing B16-F10 melanoma lesions. NPS permanently eliminated up to 91% of all tumor lesions with a single treatment compared to cryoablation that only eliminated up to 66%. Importantly, NPS permanently eliminated these lesions with no recurrence and with minimal dermal fibrosis, underlying muscle atrophy, permanent hair follicle loss or other markers of permanent skin damage. Conclusions These findings suggest that NPS is a promising new modality for the clearance of melanoma tumors and is a more efficacious, less damaging approach than cryoablative methods for the treatment of aggressive malignant tumors.
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Affiliation(s)
- Amanda McDaniel
- Department of Biology, Pulse Biosciences, Hayward, CA, United States,*Correspondence: Amanda McDaniel, ; Richard Nuccitelli,
| | - Bruce Freimark
- Department of Biology, Pulse Biosciences, Hayward, CA, United States
| | - Cebrina Navarro
- Department of Biology, Pulse Biosciences, Hayward, CA, United States
| | | | - Dacia Gonzalez
- Department of Biology, Pulse Biosciences, Hayward, CA, United States
| | - Keith Linder
- Department of Dermatopathology, Linder Pathology Services, Raleigh, NC, United States
| | - Richard Nuccitelli
- Department of Biology, Pulse Biosciences, Hayward, CA, United States,*Correspondence: Amanda McDaniel, ; Richard Nuccitelli,
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Dhaliwal A, Saghir SM, Mashiana HS, Braseth A, Dhindsa BS, Ramai D, Taunk P, Gomez-Esquivel R, Dam A, Klapman J, Adler DG. Endoscopic cryotherapy: Indications, techniques, and outcomes involving the gastrointestinal tract. World J Gastrointest Endosc 2022; 14:17-28. [PMID: 35116096 PMCID: PMC8788170 DOI: 10.4253/wjge.v14.i1.17] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 10/31/2021] [Accepted: 12/25/2021] [Indexed: 02/06/2023] Open
Abstract
Endoscopic cryotherapy is a technique utilized for the ablation of target tissue within the gastrointestinal tract. A cryotherapy system utilizes the endoscopic application of cryogen such as liquid nitrogen, carbon dioxide or liquid nitrous oxide. This leads to disruption of cell membranes, apoptosis, and thrombosis of local blood vessels within the target tissue. Several trials utilizing cryotherapy for Barrett's esophagus (BE) with variable dysplasia, gastric antral vascular ectasia (GAVE), esophageal carcinoma, radiation proctitis, and metastatic esophageal carcinomas have shown safety and efficacy. More recently, liquid nitrogen cryotherapy (cryodilation) was shown to be safe and effective for the treatment of a benign esophageal stricture which was refractory to dilations, steroid injections, and stenting. Moreover, liquid nitrogen cryotherapy is associated with less post procedure pain as compared to radiofrequency ablation in BE with comparable ablation rates. In patients with GAVE, cryotherapy was found to be less tedious as compared to argon plasma coagulation. Adverse events from cryotherapy most commonly include chest pain, esophageal strictures, and bleeding. Gastric perforations did occur as well, but less often. In summary, endoscopic cryotherapy is a promising and growing field, which was first demonstrated in BE, but the use now spans for several other disease processes. Larger randomized controlled trials are needed before its role can be established for these different diseases.
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Affiliation(s)
- Amaninder Dhaliwal
- Division of Gastroenterology and Advanced Endoscopy, McLeod Regional Medical Center, Florence, SC 29501, United States
| | - Syed M Saghir
- Division of Gastroenterology, Creighton University School of Medicine, Omaha, NE 68124, United States
| | - Harmeet S Mashiana
- Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198-2000, United States
| | - Annie Braseth
- Division of Gastroenterology, University of Iowa, Iowa City, IA 52242-1009, United States
| | - Banreet S Dhindsa
- Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198-2000, United States
| | - Daryl Ramai
- Division of Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, UT 84132, United States
| | - Pushpak Taunk
- Division of Gastroenterology, USF Health, Tampa, FL 33612, United States
| | | | - Aamir Dam
- Division of Gastroenterology and Hepatology, Moffitt Cancer Center, Tampa, FL 33612, United States
| | - Jason Klapman
- Gastrointestinal Tumor Program, Moffitt Cancer Center, Tampa, FL 33612, United States
| | - Douglas G Adler
- Center for Advanced Therapeutic Endoscopy, Porter Adventist Hospital, Center Health, Denver, CO 80210, United States
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Alzubaidi SJ, Liou H, Saini G, Segaran N, Scott Kriegshauser J, Naidu SG, Patel IJ, Oklu R. Percutaneous Image-Guided Ablation of Lung Tumors. J Clin Med 2021; 10:5783. [PMID: 34945082 PMCID: PMC8707332 DOI: 10.3390/jcm10245783] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/03/2021] [Accepted: 12/07/2021] [Indexed: 12/22/2022] Open
Abstract
Tumors of the lung, including primary cancer and metastases, are notoriously common and difficult to treat. Although surgical resection of lung lesions is often indicated, many conditions disqualify patients from being surgical candidates. Percutaneous image-guided lung ablation is a relatively new set of techniques that offers a promising treatment option for a variety of lung tumors. Although there have been no clinical trials to definitively compare its efficacy to those of traditional treatments, lung ablation is widely practiced and generally accepted to be safe and effective. Especially encouraging results have recently emerged for cryoablation, one of the newer ablative techniques. This article reviews the indications, techniques, contraindications, and complications of percutaneous image-guided ablation of lung tumors with special attention to cryoablation and its recent developments in protocol optimization.
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Affiliation(s)
- Sadeer J. Alzubaidi
- Department of Radiology, Mayo Clinic, Phoenix, AZ 85054, USA; (J.S.K.); (S.G.N.); (I.J.P.); (R.O.)
| | - Harris Liou
- Alix School of Medicine, Mayo Clinic, Scottsdale, AZ 85259, USA;
| | - Gia Saini
- Division of Vascular and Interventional Radiology, Laboratory for Patient Inspired Engineering, Mayo Clinic, Phoenix, AZ 85054, USA; (G.S.); (N.S.)
| | - Nicole Segaran
- Division of Vascular and Interventional Radiology, Laboratory for Patient Inspired Engineering, Mayo Clinic, Phoenix, AZ 85054, USA; (G.S.); (N.S.)
| | - J. Scott Kriegshauser
- Department of Radiology, Mayo Clinic, Phoenix, AZ 85054, USA; (J.S.K.); (S.G.N.); (I.J.P.); (R.O.)
| | - Sailendra G. Naidu
- Department of Radiology, Mayo Clinic, Phoenix, AZ 85054, USA; (J.S.K.); (S.G.N.); (I.J.P.); (R.O.)
| | - Indravadan J. Patel
- Department of Radiology, Mayo Clinic, Phoenix, AZ 85054, USA; (J.S.K.); (S.G.N.); (I.J.P.); (R.O.)
| | - Rahmi Oklu
- Department of Radiology, Mayo Clinic, Phoenix, AZ 85054, USA; (J.S.K.); (S.G.N.); (I.J.P.); (R.O.)
- Division of Vascular and Interventional Radiology, Laboratory for Patient Inspired Engineering, Mayo Clinic, Phoenix, AZ 85054, USA; (G.S.); (N.S.)
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Percutaneous cryoablation of adrenal metastases: technical feasibility and safety. Abdom Radiol (NY) 2021; 46:2805-2813. [PMID: 33543315 DOI: 10.1007/s00261-020-02848-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 10/20/2020] [Accepted: 10/30/2020] [Indexed: 11/27/2022]
Abstract
PURPOSE To assess the technical feasibility and outcomes of adrenal metastases cryoablation. MATERIALS AND METHODS This is an IRB approved retrospective review of adrenal metastases cryoablation between April 2003 and October 2018. Forty percutaneous cryoablation procedures were performed on 40 adrenal metastases in 34 patients. Histology, tumor size, ablation zone size, major vessel proximity, local recurrences, complications, and anesthesia-managed hypertension monitoring was collected. Complications were graded according to the Common Terminology of Complications and Adverse Events (CTCAE). RESULTS Mean tumor and ablation size was 3.2 cm and 5.2 cm, respectively. Local recurrence rate was 10.0% (N = 4/40) for a mean follow-up time of 1.8 years. Recurrences for tumors > 3 cm (21.0%, N = 4/19) was greater than for tumors ≤ 3 cm (0.0%, N = 0/21) (p = 0.027). Proximity of major vasculature (i.e., IVC & aorta) did not statistically effect recurrence rates (p = 0.52), however, those that recurred near vasculature were > 4 cm. Major complication (≥ grade 3) rate was 5.0% (N = 2/40), with one major complication attributable to the procedure. Immediate escalation of blood pressure during the passive stick phase (between freeze cycles) or post procedure thaw phase was greater in patients with residual adrenal tissue (N = 21/38) versus masses replacing the entire adrenal gland (N = 17/38), (p = 0.0020). Lower blood pressure elevation was noted in patients with residual adrenal tissue who were pre-treated with alpha blockade (p = 0.015). CONCLUSIONS CT-guided percutaneous cryoablation is a safe, effective and low morbidity alternative for patients with adrenal metastases. Transient hypertension is related only to residual viable adrenal tissue but can be safely managed and prophylactically treated.
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Ma J, Yu X, Lv J, Lin D, Lin J, Bai Y, Wang Y, Li X, Dong J. Cryotherapy mediates histopathological and microstructural changes during the treatment of skin and subcutaneous tumors in dogs. Cryobiology 2020; 98:164-171. [PMID: 33248049 DOI: 10.1016/j.cryobiol.2020.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 11/21/2020] [Accepted: 11/22/2020] [Indexed: 10/22/2022]
Abstract
The therapeutic effects of cryotherapy on skin and subcutaneous tumors in dogs were retrospectively studied in 20 dogs with 37 tumor lesions, of which 30 were benign and seven were malignant. Our results showed that during follow-up, 94.5% of lesions were completely exfoliated, without relapse or metastasis (mean time = 245.7 days). To investigate the effects of cryotherapy, we compared histopathological observations and microstructural changes in healthy tissues and tumor tissues, before and after cryotherapy. After cryotherapy, both normal skin and tumor tissue exhibited edema and hyperemia, with inflammatory cell infiltration. The cell nuclei exhibited pyknosis, disintegration and necrosis, and tight junctions were decreased in size. Cell morphology was varied, along with fragmented cell nuclear envelopes, crenulated nuclei and indistinct and necrotic intracellular organelles. Vacuoles were apparent in the cytoplasm and intercellular desmosomes were absent. These observations suggested that cryosurgery inhibited skin and subcutaneous tumors via cold-induced injury to cells, and cellular microenvironment changes induced by apoptosis. The results suggested that cryosurgery prevented skin and subcutaneous tumors via cold-induced injury to cells, and cellular microenvironment changes induced by apoptosis. We believe these data will provide general cryotherapy guidance to scientists and veterinary surgeons.
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Affiliation(s)
- Jiquan Ma
- Gateway Medical Innovation Center, Shanghai, China
| | - Xuezhi Yu
- College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Jinbao Lv
- Beijing Jiachong Biotechnology Co., Ltd, Beijing, China
| | - Degui Lin
- College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Jiahao Lin
- College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Yang Bai
- College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Yingyun Wang
- College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Xinqiu Li
- College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Jun Dong
- College of Veterinary Medicine, China Agricultural University, Beijing, China.
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El Hawary M, Bassiouny DA, Esmat S, Sobhi R, Saleh MA, AbdelHalim D, Hegazy R, Gawdat H, Ragab N, Samir N, Sany I. Recipient site preparation by cryoblebbing in melanocyte keratinocyte transplantation procedure over the fingers in vitiligo: A pilot study. Dermatol Ther 2020; 33:e14199. [PMID: 32798282 DOI: 10.1111/dth.14199] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 07/15/2020] [Accepted: 08/04/2020] [Indexed: 11/28/2022]
Abstract
Surgical treatment of vitiligo lesions over the fingers has poor outcome. In this intra-patient comparative study, 12 patients with stable non-segmental vitiligo (NSV) affecting the middle three fingers of one hand were included. Three variations were used in treatment of finger vitiligo lesions: minipuch grafting, melanocytes keratinocyte transplantation procedure (MKTP) preceded by cryoblebbing or full CO2 laser resurfacing of the recipient site. Liquid nitrogen was used to create blebs in one finger 24 hours before therapy. On the following day, the second finger was treated by minipunch grafting and the third finger was resurfaced by CO2 laser. A suspension was prepared and 0.1 mL was injected into each cryobleb. It was also applied to the resurfaced skin. All patients underwent topical PUVA therapy and were followed-up for 12 months. Ten cases with 52 lesions completed the follow-up period. About 4/18 lesions treated by cryoblebbing followed by MKTP showed ≥75% repigmentation while only 1/17 lesions treated by laser resurfacing + MKTP and 1/17 lesions treated by minipunch grafting showed 30% and 10% repigmentation, respectively. No complications occurred in MKTP treated lesions. Cryoblebbing of the recipient site seems to improve the outcome of MKTP in lesions over the fingers in stable NSV.
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Affiliation(s)
- Marwa El Hawary
- The Department of Dermatology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Dalia Ahmed Bassiouny
- The Department of Dermatology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Samia Esmat
- The Department of Dermatology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rehab Sobhi
- The Department of Dermatology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Marwah Adly Saleh
- The Department of Dermatology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Dalia AbdelHalim
- The Department of Dermatology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rehab Hegazy
- The Department of Dermatology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Heba Gawdat
- The Department of Dermatology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Nanis Ragab
- The Department of Dermatology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Nesrin Samir
- The Department of Dermatology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Iman Sany
- The Department of Dermatology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt
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Critical review of multidisciplinary non-surgical local interventional ablation techniques in primary or secondary liver malignancies. J Contemp Brachytherapy 2019; 11:589-600. [PMID: 31969919 PMCID: PMC6964346 DOI: 10.5114/jcb.2019.90466] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 10/15/2019] [Indexed: 12/21/2022] Open
Abstract
Local non-surgical interventional percutaneous ablation represents nowadays an important part of the potential treatment strategies. Although surgical ablation represents the gold standard, in the past decade there was an expansion in the use of non-surgical ablative techniques: radiofrequency, microwave, laser, cryoablation, irreversible electroporation, and interventional radiotherapy (brachytherapy) in primary as well as secondary liver cancers. With the growing experience in the field, there was implemented a new pillar for cancer treatment, together with surgery, chemotherapy as well as radiotherapy, so-called interventional oncology (IO). To date, there are no published papers regarding a comparative interdisciplinary evaluation of all these non-surgical interventional local ablation therapies. Our paper offers a critical interdisciplinary overview of the treatments in both primary and secondary liver tumors, including from a cost-effective point of view. Furthermore, the present status of education in IO and a comparison of actual economic aspects of the treatments are also provided.
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Abstract
OBJECTIVE Imaging plays a key role in the assessment of patients before, during, and after percutaneous cryoablation of hepatic tumors. Intra-procedural and early post-procedure imaging with CT and MRI is vital to the assessment of technical success including adequacy of ablation zone coverage. Recognition of the normal expected post-procedure findings of hepatic cryoablation such as ice ball formation, hydrodissection, and the normal appearance of the ablation zone is crucial to be able to differentiate from complications including vascular, biliary, or non-target organ injury. Delayed imaging is essential for determination of clinical effectiveness and detection of unexpected findings such as residual unablated tumor and local tumor progression. The purpose of this article is to review the spectrum of expected and unexpected imaging findings that may occur during or after percutaneous cryoablation of hepatic tumors. CONCLUSION Differentiating expected from unexpected findings during and after hepatic cryoablation helps radiologists identify residual or recurrent tumor and detect procedure-related complications.
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Abstract
Understanding and management of vascular anomalies has always been intriguing. These disorders exhibit an expected pattern of clinical presentation and progression, and characteristic imaging findings. Significant progress in understanding and treating patients with vascular anomalies has been made in the past quarter century. Newer multidisciplinary domains for treating these disorders with medical drugs and less invasive image-guided or surgical procedures are constantly evolving. Vascular anomalies can exhibit aggressive tumor-like behavior resulting in recurrence or persistent symptoms after treatment. Thermal ablation has been widely used in tumor treatment. This has generated interest on using thermal ablation for treating vascular anomalies. Percutaneous image-guided cryoablation is increasingly used for this purpose as compared with other ablation technologies. Availability of small caliber cryoprobes and the ability to monitor the freeze zone in real time have made this an attractive option to interventional radiologists. These experiences are relatively new and limited. It is helpful to understand the emerging role of this technology in the treatment of vascular anomalies.
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Affiliation(s)
- Raja Shaikh
- Department of Radiology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts
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Aoun HD, Littrup PJ, Jaber M, Memon F, Adam B, Krycia M, Prus M, Heath E, Pontes E. Percutaneous Cryoablation of Renal Tumors: Is It Time for a New Paradigm Shift? J Vasc Interv Radiol 2017; 28:1363-1370. [PMID: 28844831 DOI: 10.1016/j.jvir.2017.07.013] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 07/11/2017] [Accepted: 07/12/2017] [Indexed: 12/22/2022] Open
Abstract
PURPOSE To retrospectively assess long-term outcomes of percutaneous renal cryoablation, including factors affecting complications and local recurrence rates. MATERIALS AND METHODS A total of 357 computed tomographic (CT) fluoroscopy-guided percutaneous cryoablation procedures were performed for 382 masses in 302 outpatients; 347 were biopsy-proven renal-cell carcinoma (RCC) or Bosniak category > III masses (n = 28). Benign pathologic conditions (n = 18) or metastatic non-RCC disease (n = 17) were included to analyze procedural complication rate, but recurrence rates, tumor staging, and nephrometry score were limited to RCCs. The average tumor diameter was 2.9 cm (range, 1-10.3 cm), and median nephrometry score for RCC was 8 (mean, 7.4). Protection of adjacent vital structures was performed in 34% of procedures (n = 121), and ureteral stent placement was performed for 9.2% (n = 33). All major complications were graded per surgical Clavien-Dindo criteria. RESULTS The average CT-visible cryoablation zone diameter was 5 cm (range, 2.5-10.5 cm). Grade ≥ 3 complications occurred in 2.8% of procedures (n = 10), and appeared related to only high nephrometry scores (P = .0086) and larger tumors (P = .0034). No significant changes in renal function before and after the procedure were noted (P = .18). At a mean follow-up of 31.8 months, the local tumor recurrence rate was 3.2% (11 of 347) for RCC, and no significant difference was noted between tumors larger or smaller than 3 cm (P = .15). The difference reached significance only among the small number of stage ≥ T2 RCC tumors (P = .0039). CONCLUSIONS Long-term follow-up of percutaneous renal cryoablation demonstrates low recurrence rates with preserved renal function, even for patients with high nephrometry scores and body mass index, assuming thorough cytotoxic technique and protection measures.
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Affiliation(s)
- Hussein D Aoun
- Imaging Division, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
| | - Peter J Littrup
- Department of Diagnostic Imaging, Brown University, Rhode Island Hospital, Providence, Rhode Island
| | - Mohamed Jaber
- Department of Radiology, Wayne State Medical School, Detroit, Michigan
| | - Fatima Memon
- Department of Radiology, Wayne State Medical School, Detroit, Michigan
| | - Barbara Adam
- Imaging Division, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
| | - Mark Krycia
- Department of Radiology, Wayne State Medical School, Detroit, Michigan
| | - Matthew Prus
- Imaging Division, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
| | - Elisabeth Heath
- Division of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
| | - Edson Pontes
- Division of Urology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
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Parsi MA, Trindade AJ, Bhutani MS, Melson J, Navaneethan U, Thosani N, Trikudanathan G, Watson RR, Maple JT. Cryotherapy in gastrointestinal endoscopy. VIDEOGIE : AN OFFICIAL VIDEO JOURNAL OF THE AMERICAN SOCIETY FOR GASTROINTESTINAL ENDOSCOPY 2017; 2:89-95. [PMID: 29905303 PMCID: PMC5991494 DOI: 10.1016/j.vgie.2017.01.021] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Key Words
- AVM, arteriovenous malformation
- BE, Barrett’s esophagus
- CE-D, complete elimination of dysplasia
- CE-IM, complete elimination of intestinal metaplasia
- CPT, Current Procedural Terminology
- GAVE, gastric antral vascular ectasia
- HGD, high-grade dysplasia
- RFA, radiofrequency ablation
- RP, radiation proctopathy
- RVU, relative value unit
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Percutaneous cryoablation of hepatic tumors: long-term experience of a large U.S. series. Abdom Radiol (NY) 2016; 41:767-80. [PMID: 26960728 DOI: 10.1007/s00261-016-0687-x] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE To report our long-term experience with percutaneous cryotherapy for primary and metastatic liver tumors, including historical perspectives on complications over time and local recurrence rates. MATERIALS AND METHODS Following IRB approval under HIPAA compliance, 342 CT fluoroscopic-guided, percutaneous cryotherapy procedures were performed for 443 masses in 212 outpatients with hepatocellular carcinoma (HCC; N = 36), or metastatic disease (N = 176), grouped as colorectal carcinoma (CRC) and non-CRC metastases. Tumor and ablation sizes were noted in relation to adjacent vasculature. All complications were graded according to standardized criteria. Patients were followed by CT and/or MRI at 1, 3, 6, 12, 18, 24 months and yearly thereafter. Local recurrences were defined as either "procedural" within the ice ablation zone, or "satellite" within 1 cm of the ablation rim to evaluate recurrence patterns. RESULTS Average tumor diameter of 2.8 cm was treated by average cryoprobe number of 4.5, which produced CT-visible ice ablation zone diameters averaging 5.2 cm. Grade >3 complications were primarily hematologic [N = 20/342; (5.8%)], and appeared related to pre-procedural anemia/thrombocytopenia, carcinoid tumor type, and large ablation volumes. No significant central biliary leak, strictures, or bilomas were noted. At a mean follow-up of 1.8 years, local tumor recurrences were 5.5%, 11.1%, and 9.4% for HCC, CRC, and non-CRC metastases, respectively, consisting mainly of satellite foci. No significant difference was noted for local recurrences near major blood vessels or tumors >3 cm diameter. CONCLUSIONS Percutaneous hepatic cryotherapy is a well-visualized, safe procedure that produces very low local recurrence rates, even for tumors near vasculature and diameters over 3 cm. Cryoablation deserves to be in the armamentarium of percutaneous hepatic ablation, especially with careful patient selection for tumors <4 cm and patients with platelet counts >100,000. Percutaneous hepatic cryoablation represents a highly flexible technique with particular benefits near central biliary structures and/or adjacent crucial structures.
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Kasuya A, Ohta I, Tokura Y. Structural and immunological effects of skin cryoablation in a mouse model. PLoS One 2015; 10:e0123906. [PMID: 25821968 PMCID: PMC4379110 DOI: 10.1371/journal.pone.0123906] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Accepted: 02/27/2015] [Indexed: 11/18/2022] Open
Abstract
Cryoablation is therapeutically applied for various disorders in several organs, and skin diseases are typical targets as this cryotherapy has been widely used for viral warts, benign tumors, and actinic keratosis. The main mechanisms of cryoablation consist of direct freezing effect on skin constituents, thrombosis formation in microcirculation, and subsequent immunological responses. Among them, however, the immunological mechanism remains unelucidated, and it is an issue how the direct freezing injury induces immunological consequences. We established a mouse cryoablation model with liquid nitrogen applied to the shaved back skin, and used this system to study the immunological excitement. After application of liquid nitrogen, the thermal decrease ratio was -25°C/sec or less and the lowest temperature was less than -100°C, which was sufficient to induce ulceration. Destruction of cornified layer and necrosis of epidermal cells were observed in transmission electron microscopy image, and increased transepidermal water loss and skin permeability were detected by the functional measurements. By flow cytometry, antigen-presenting dendritic cells (DCs), including PDCA1+B220+CD19- plasmacytoid DCs (pDCs) and CD11c+ myeloid DCs, as well as neutrophils and macrophages were increased in subcutaneous tissue. In parallel, the mRNA expressions of interferon α1 which are known as pDC-producing cytokines, was elevated. We also found marked degranulation of mast cells, providing a possibility that released histamine attracts pDCs. Finally, FITC migration assay revealed that pDCs and CD11c+ DCs emigrated from the cryoablated skin to the draining lymph nodes. Our study suggests that cryoablation induces destruction of the barrier/epidermis, accumulation of pDCs and CD11c+ DCs to the skin, and migration of DCs to regional lymph nodes. Viral elements or tumor cell lysates released from damaged keratinocytes may stimulate the DCs, thereby leading to antiviral or antitumor effect.
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Affiliation(s)
- Akira Kasuya
- Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Isao Ohta
- Ultrastructural Morphology Laboratory, Research Equipment Centre, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yoshiki Tokura
- Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
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Ridge CA, Solomon SB, Thornton RH. Thermal ablation of stage I non-small cell lung carcinoma. Semin Intervent Radiol 2014; 31:118-24. [PMID: 25053863 DOI: 10.1055/s-0034-1373786] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Ablation options for the treatment of localized non-small cell lung carcinoma (NSCLC) include radiofrequency ablation, microwave ablation, and cryotherapy. Irreversible electroporation is a novel ablation method with the potential of application to lung tumors in risky locations. This review article describes the established and novel ablation techniques used in the treatment of localized NSCLC, including mechanism of action, indications, potential complications, clinical outcomes, postablation surveillance, and use in combination with other therapies.
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Affiliation(s)
- Carol A Ridge
- Department of Radiology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Stephen B Solomon
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Raymond H Thornton
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
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18
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Yu H, Burke CT. Comparison of percutaneous ablation technologies in the treatment of malignant liver tumors. Semin Intervent Radiol 2014; 31:129-37. [PMID: 25071303 PMCID: PMC4078184 DOI: 10.1055/s-0034-1373788] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Tumor ablation is a minimally invasive technique used to deliver chemical, thermal, electrical, or ultrasonic damage to a specific focal tumor in an attempt to achieve substantial tumor destruction or complete eradication. As the technology continues to advance, several image-guided tumor ablations have emerged to effectively manage primary and secondary malignancies in the liver. Percutaneous chemical ablation is one of the oldest and most established techniques for treating small hepatocellular carcinomas. However, this technique has been largely replaced by newer modalities including radiofrequency ablation, microwave ablation, laser-induced interstitial thermotherapy, cryoablation, high-intensity-focused ultrasound ablation, and irreversible electroporation. Because there exist significant differences in underlying technological bases, understanding each mechanism of action is essential for achieving desirable outcomes. In this article, the authors review the current state of each ablation method including technological and clinical considerations.
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Affiliation(s)
- Hyeon Yu
- Division of Vascular and Interventional Radiology, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Charles T. Burke
- Division of Vascular and Interventional Radiology, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
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Littrup PJ, Bang HJ, Currier BP, Goodrich DJ, Aoun HD, Heilbrun LK, Adam BA. Soft-tissue cryoablation in diffuse locations: feasibility and intermediate term outcomes. J Vasc Interv Radiol 2013; 24:1817-25. [PMID: 24060437 DOI: 10.1016/j.jvir.2013.06.025] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2013] [Revised: 06/14/2013] [Accepted: 06/27/2013] [Indexed: 11/17/2022] Open
Abstract
PURPOSE To assess whether diverse tumor location(s) show differences in percutaneous cryoablation (PCA) outcomes of cancer control, morbidity, and ablation volume reduction for many soft-tissue tumor types. MATERIALS AND METHODS A total of 220 computed tomography (CT)- and/or ultrasonography-guided percutaneous cryotherapy procedures were performed for 251 oligometastatic tumors from multiple primary cancers in 126 patients. Tumor location was grouped according to regional sites: retroperitoneal, superficial, intraperitoneal, bone, and head and neck. PCA complications were graded according to Common Terminology Criteria for Adverse Events (version 4.0). Local tumor recurrence and involution were calculated from ablation zone measurements, grouped into 1-, 3-, 6-, 12-, 18-, and 24-month (or later) statistical bins. RESULTS Tumor and procedure numbers for each site were 75 and 69 retroperitoneal, 76 and 62 superficial, 39 and 32 intraperitoneal, 34 and 34 bone, and 27 and 26 head and neck. Average diameters of tumor and visible ice during ablation were 3.4 and 5.5 cm, respectively. Major complications (ie, grade >3) attributable to PCA occurred after five procedures (2.3%). At 11 months average follow-up (range, 0-82 mo), a 10% total recurrence rate (26 of 251) was noted; three occurred within the ablation zone, for a local progression rate of 1.2%. Average time to recurrence was 4.9 months, and, at 21 months, the initial ablation zone had reduced in volume by 93%. CONCLUSIONS CT-guided PCA is a broadly safe, effective local cancer control option for oligometastatic disease with soft-tissue tumors in most anatomic sites. Other than bowel and nerve proximity, PCA also shows good healing if proper visualization and precautions are followed.
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Affiliation(s)
- Peter J Littrup
- Department of Radiology, Karmanos Cancer Center, Detroit, Michigan.
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20
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Ni H, Yang M, Guo Z, Zhang T. Sorafenib combined with cryoablation to treat unresectable hepatocellular carcinoma. Chin J Cancer Res 2013; 23:188-93. [PMID: 23467380 PMCID: PMC3587556 DOI: 10.1007/s11670-011-0188-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2011] [Accepted: 04/26/2011] [Indexed: 01/08/2023] Open
Abstract
Objective To evaluate the efficacy and tolerability of sorafenib combined with cryoablation in treating unresectable hepatocellular carcinoma (HCC). Methods Patients with unresectable advanced HCC received cryoablation and sorafenib at a dose of 400 mg twice daily in 4-week cycles on the same day of the cryoablation. Tumor response, median overall survival and the median time to radiological progression were calculated and the toxicity was evaluated. Results Seventy-eight patients with unresectable HCC were involved in this study. The median age was 52 years (range, 22-81 years). The Eastern Cooperative Oncology Group (ECOG) performance status scores were 0 (39.7%), 1 (55.1%), and 2 (5.1%). Nine (11.5%) patients were at Barcelona clinic liver cancer (BCLC) stage A, twenty-four (30.8%) patients were at stage B and 45 (57.7%) patients were at stage C. Five (6.4%) achieved partial responses, and 34 (43.6%) achieved stable disease. The median time to progression (TTP) for all enrolled patients was 6.6 months and the median overall survival (OS) was 12.2 months. Conclusion Cryoablation combined with sorafenib demonstrates good efficacy and acceptable tolerability in treating unresectable advanced HCC patients.
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Affiliation(s)
- Hong Ni
- Department of Interventional Therapy, Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, China
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21
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Irreversible electroporation near the heart: ventricular arrhythmias can be prevented with ECG synchronization. AJR Am J Roentgenol 2011; 196:W330-5. [PMID: 21343484 DOI: 10.2214/ajr.10.4490] [Citation(s) in RCA: 135] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Irreversible electroporation is a nonthermal ablative tool that uses direct electrical pulses to create irreversible membrane pores and cell death. The ablation zone is surrounded by a zone of reversibly increased permeability; either zone can cause cardiac arrhythmias. Our purpose was to establish a safety profile for the use of irreversible electroporation close to the heart. MATERIALS AND METHODS The effect of unsynchronized and synchronized (with the R wave on ECG) irreversible electroporation in swine lung and myocardium was studied in 11 pigs. Twelve lead ECG recordings were analyzed by an electrophysiologist for the presence of arrhythmia. Ventricular arrhythmias were categorized as major events. Minor events included all other dysrhythmias or ECG changes. Cardiac and lung tissue was submitted for histopathologic analysis. Electrical field modeling was performed to predict the distance from the applicators over which cells show electroporation-induced increased permeability. RESULTS At less than or equal to 1.7 cm from the heart, fatal (major) events occurred with all unsynchronized irreversible electroporation. No major and three minor events were seen with synchronized irreversible electroporation. At more than 1.7 cm from the heart, two minor events occurred with only unsynchronized irreversible electroporation. Electrical field modeling correlates well with the clinical results, revealing increased cell membrane permeability up to 1.7 cm away from the applicators. Complete lung ablation without intervening live cells was seen. No myocardial injury was seen. CONCLUSION Unsynchronized irreversible electroporation close to the heart can cause fatal ventricular arrhythmias. Synchronizing irreversible electroporation pulse delivery with absolute refractory period avoids significant cardiac arrhythmias.
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Cryotherapy of the liver: A histological review. Cryobiology 2010; 61:1-9. [DOI: 10.1016/j.cryobiol.2010.06.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2010] [Revised: 04/23/2010] [Accepted: 06/10/2010] [Indexed: 01/13/2023]
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Erinjeri JP, Clark TWI. Cryoablation: mechanism of action and devices. J Vasc Interv Radiol 2010; 21:S187-91. [PMID: 20656228 PMCID: PMC6661161 DOI: 10.1016/j.jvir.2009.12.403] [Citation(s) in RCA: 247] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2009] [Revised: 11/23/2009] [Accepted: 12/30/2009] [Indexed: 12/18/2022] Open
Abstract
Cryoablation refers to all methods of destroying tissue by freezing. Cryoablation causes cellular damage, death, and necrosis of tissues by direct mechanisms, which cause cold-induced injury to cells, and indirect mechanisms, which cause changes to the cellular microenvironment and impair tissue viability. Cellular injury, both indirect and direct, can be influenced by four factors: cooling rate, target temperature, time at target temperature, and thawing rate. In this review, the authors describe the mechanisms of cellular injury that occur with cryoablation, the major advantages and disadvantages of cryoablation compared with other thermal ablation techniques, and the current commercially available cryoablation ablation systems.
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Affiliation(s)
- Joseph P Erinjeri
- Interventional Radiology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, H118, New York, NY 10065, USA.
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Affiliation(s)
- Jennifer L. Young
- Department of Urology, University of California Irvine, Orange, California
| | - Ralph V. Clayman
- Department of Urology, University of California Irvine, Orange, California
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25
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Littrup PJ, Ahmed A, Aoun HD, Noujaim DL, Harb T, Nakat S, Abdallah K, Adam BA, Venkatramanamoorthy R, Sakr W, Pontes JE, Heilbrun LK. CT-guided percutaneous cryotherapy of renal masses. J Vasc Interv Radiol 2008; 18:383-92. [PMID: 17377184 DOI: 10.1016/j.jvir.2006.12.007] [Citation(s) in RCA: 114] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
PURPOSE To assess the results of initial and current techniques for percutaneous renal cryotherapy, including long-term imaging outcomes. MATERIALS AND METHODS Computed tomography (CT)-guided percutaneous cryotherapy was performed on 49 masses in 48 outpatients and procedure comfort noted for each. These 49 masses included 36 primary renal cell carcinomas (RCCs), 3 oncocytomas, 1 angiomyolipoma, 6 renal inflammatory lesions, 2 benign parenchymal changes, and 1 colon cancer metastasis. All complications were graded according to standardized criteria. RESULTS Patients received only local anesthesia and moderate sedation during the procedure and were discharged with minimal discomfort within 4-6 hours. All cryotherapy zones were well defined by CT during ablation as hypodense ice with an average diameter of 5.3 cm, covering an average tumor size of 3.3 cm. Average ablation zone diameters showed significant reduction over time (P < .001), becoming significantly less than the original tumor size by 12 months (P < .05). Major and minor complications were seen in 3 (6%) and 11 (22%) procedures, respectively. At a mean follow-up of 1.6 years (range, 1 week to 3.8 years) for primary RCC patients, four failures (11.1%) by imaging criteria were noted, but one proved to be inflammatory tissue at re-biopsy (estimated neoplastic failure rate = 3/36 = 8.3%). CONCLUSIONS Percutaneous renal cryotherapy is a well-tolerated outpatient procedure that allows safe, CT monitoring of ice formation beyond visible tumor margins. With appropriate cryoprobe placements, a low failure rate appears less dependent on tumor size or location. Ablation volume involution was >80% after 6 months.
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Affiliation(s)
- Peter J Littrup
- Biostatistics Unit, Wayne State University, 110 East Warren, Hudson-Weber Building, Suite 504, Detroit, MI 48201, USA.
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26
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Kim C, O'Rourke AP, Will JA, Mahvi DM, Webster JG. Finite-element analysis of hepatic cryoablation around a large blood vessel. IEEE Trans Biomed Eng 2008; 55:2087-93. [PMID: 18632371 DOI: 10.1109/tbme.2008.919837] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Cryoablation is a minimally invasive ablation technique for primary and metastatic hepatic tumors. Inadequate freezing around large blood vessels due to the warm blood flow can lead to local recurrence, and thus, necessitates close application of a cryoprobe to the large blood vessels. In this study, we constructed a perfusion model with an ex vivo bovine liver and ablated the tissue around a large blood vessel with one or two cryoprobes applied to the side of the vessel. The finite-element computer model developed in our previous study was modified to include a blood vessel and its convective heat transfer to the vicinity of the blood vessel. We compared the predicted simulation results to those acquired from this ex vivo perfusion model. The results indicate that blood vessels act as a heat source and generate steep temperature profiles in the area next to the large blood vessel. After validation, the maximum allowable distance between the cryoprobe and the large blood vessel for successful cryoablation was presented. The results of this study should be considered when placing cryoprobes in the vicinity of large blood vessels.
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Affiliation(s)
- Cheolkyun Kim
- Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53706, USA.
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27
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Korpan NN. Cryosurgery: early ultrastructural changes in liver tissue in vivo. J Surg Res 2008; 153:54-65. [PMID: 18486151 DOI: 10.1016/j.jss.2008.02.063] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2007] [Revised: 02/21/2008] [Accepted: 02/23/2008] [Indexed: 10/22/2022]
Abstract
BACKGROUND Experimental observations with regard to freezing in vitro cell lines and fluid systems led to the application of low temperatures to in vivo biological systems. For the first time, this report describes the cryosurgical response of liver parenchyma and the early ultrastructural cellular changes in liver tissue, i.e., cryosurgery, in vivo. MATERIALS AND METHODS Forty-eight animals were used for the experiment. The dogs were divided into four groups. In group A, the liver tissue was frozen to -80 degrees C and in group B, to -180 degrees C. Temperatures of -80 degrees C and -180 degrees C in contact with liver tissue was selected for cryosurgical exposure. For transmission electron microscopy, the specimens were taken immediately and 1 h after the finishing of the freeze-thaw cycles intraoperatively. Further, the next specimens were taken in 24 h, this time also intraoperatively. RESULTS The electronic microscopic analysis showed that, after local cryodestruction at temperatures of -80 degrees C and -180 degrees C, similar processes occurred within the liver tissue in the early postcryosurgical phase-immediately and 1 h after cryosurgical session. The hepatocytes in the center of the cryozone changed upon thawing. Ultrastructural changes in the hepatic cells, where the first signs of dystrophic processes had been noticed, were increased. CONCLUSIONS Our new insights prove on the cell level that suddenly and progressively damaged liver cells in the postcryosurgical zone lead to aseptic cryoaponecrosis and then to aseptic cryoapoptosis of vital normal tissue. The vascular capillary changes and circulatory stagnation demonstrate together with cryoaponecrosis and cryoapoptosis the anti-angiogenesis mechanisms, which are some of the main mechanisms of biological tissue injury following the low temperature exposure.
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Affiliation(s)
- Nikolai N Korpan
- International Institute for Cryosurgery, Department of Surgery, Rudolfinerhaus, Vienna, Austria.
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O'Rourke AP, Haemmerich D, Prakash P, Converse MC, Mahvi DM, Webster JG. Current status of liver tumor ablation devices. Expert Rev Med Devices 2008; 4:523-37. [PMID: 17605688 DOI: 10.1586/17434440.4.4.523] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
The liver is a common site of disease for both primary and metastatic cancer. Since most patients have a disease that is not amenable to surgical resection, tumor ablation modalities are increasingly being used for treatment of liver cancer. This review describes the current status of ablative technologies used as alternatives for resection, clinical experience with these technologies, currently available devices and design rules for the development of new devices and the improvement of existing ones. It focuses on probe design for radiofrequency ablation, microwave ablation and cryoablation, and compares the advantages and disadvantages of each ablation modality.
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Affiliation(s)
- Ann P O'Rourke
- Department of Surgery, University of Wisconsin, Madison, WI 53792, USA.
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Kim C, O'Rourke AP, Mahvi DM, Webster JG. Finite-element analysis of ex vivo and in vivo hepatic cryoablation. IEEE Trans Biomed Eng 2007; 54:1177-85. [PMID: 17605348 DOI: 10.1109/tbme.2006.889775] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Cryoablation is a widely used method for the treatment of nonresectable primary and metastatic liver tumors. A model that can accurately predict the size of a cryolesion may allow more effective treatment of tumor, while sparing normal liver tissue. We generated a computer model of tissue cryoablation using the finite-element method (FEM). In our model, we considered the heat transfer mechanism inside the cryoprobe and also cryoprobe surfaces so our model could incorporate the effect of heat transfer along the cryoprobe from the environment at room temperature. The modeling of the phase shift from liquid to solid was a key factor in the accurate development of this model. The model was verified initially in an ex vivo liver model. Temperature history at three locations around one cryoprobe and between two cryoprobes was measured. The comparison between the ex vivo result and the FEM modeling result at each location showed a good match, where the maximum difference was within the error range acquired in the experiment (< 5 degrees C). The FEM model prediction of the lesion size was within 0.7 mm of experimental results. We then validated our FEM in an in vivo experimental porcine model. We considered blood perfusion in conjunction with blood viscosity depending on temperature. The in vivo iceball size was smaller than the ex vivo iceball size due to blood perfusion as predicted in our model. The FEM results predicted this size within 0.1-mm error. The FEM model we report can accurately predict the extent of cryoablation in the liver.
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Affiliation(s)
- Cheolkyun Kim
- Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53706, USA
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Shock SA, Laeseke PF, Sampson LA, Lewis WD, Winter TC, Fine JP, Lee FT. Hepatic hemorrhage caused by percutaneous tumor ablation: radiofrequency ablation versus cryoablation in a porcine model. Radiology 2005; 236:125-31. [PMID: 15987968 DOI: 10.1148/radiol.2361040533] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
PURPOSE To determine the extent of hepatic hemorrhage caused by percutaneous cryoablation performed with a small-diameter cryoablation probe compared with that caused by percutaneous radiofrequency (RF) ablation in a porcine model. MATERIALS AND METHODS The study was pre-approved by the institutional research animal care and use committee, and husbandry and experiments complied with National Institutes of Health standards for care and use of laboratory animals. Percutaneous hepatic ablation was performed in 18 domestic pigs (mean weight, 45 kg) by using a 17-gauge (1.5-mm-diameter) RF electrode (n = 6), a cluster of three RF electrodes (n = 6), or a 13-gauge (2.4 mm-diameter) cryoprobe (n = 6). Ablation was performed in four sites per liver. Total blood loss, minimum lesion diameter, maximum lesion diameter, and lesion volume were determined for each group and compared by using analysis of variance. RESULTS Mean blood loss was 11.11 mL +/- 11.47 (standard deviation), 105.29 mL +/- 175.58, and 28.06 mL +/- 30.97 with the single RF electrode, RF electrode cluster, and cryoablation probe, respectively. Mean minimum and maximum lesion diameters were largest with the RF electrode cluster (2.40 and 3.98 cm, respectively), followed by the cryoablation probe (2.38 and 3.94 cm) and single RF electrode (1.49 and 2.63 cm). Mean minimum and maximum lesion diameters were significantly different between the single RF electrode and the RF electrode cluster, as well as between the single RF electrode and the cryoablation probe (P < .001). Mean lesion volume was largest for the RF electrode cluster (24.03 cm3), followed by those for the cryoablation probe (17.46 cm3) and single RF electrode (9.05 cm3) (single RF electrode vs cryoablation probe, P < .05). Lesion volumes were not significantly different with the RF electrode cluster versus the single RF electrode (P = .052) or with the RF electrode cluster versus the cryoablation probe (P = .381). CONCLUSION Mean blood loss from percutaneous cryoablation in this model was between that for RF ablation with the single electrode and that for RF ablation with the electrode cluster.
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Affiliation(s)
- Sarah A Shock
- Department of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave, Madison, WI 53792-3252, USA
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Wright AS, Mahvi DM. Liver directed therapies for colorectal cancer. ACTA ACUST UNITED AC 2004; 21:831-43. [PMID: 15338777 DOI: 10.1016/s0921-4410(03)21040-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Affiliation(s)
- Andrew S Wright
- Division of General Surgery, H4/724 Clinical Science Center, Madison, WI 53792-7375, USA
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Kollmar O, Richter S, Schilling MK, Menger MD, Pistorius GA. Advanced hepatic tissue destruction in ablative cryosurgery: potentials of intermittent freezing and selective vascular inflow occlusion. Cryobiology 2004; 48:263-72. [PMID: 15157775 DOI: 10.1016/j.cryobiol.2004.02.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2003] [Accepted: 02/04/2004] [Indexed: 11/17/2022]
Abstract
Recent studies indicate that cryosurgery represents a promising approach to treat non-resectable liver tumors. To improve parenchymal tissue destruction, a variety of modifications of the freeze-thaw procedure have been suggested, including repetitive freezing and portal-triad cross-clamping. The aim of the present study was to analyze whether intermittent freezing by application of a double freeze-thaw procedure or selective vascular inflow occlusion are more effective than a single freeze-thaw cycle to achieve complete hepatic tissue destruction. Using a porcine model, intrahepatic cryolesions were induced by freezing the hepatic tissue for a total of 15 min (n=6, SF). Additional animals (n=6) underwent a double freeze-thaw cycle of 7.5 min each (DF). A third group of animals (n=6) was treated by a single 15-min freeze-thaw cycle during selective vascular inflow occlusion (VO-SF). Seven days after freezing, DF did not change the volume of the cryolesion (25.4+/-1.7 cm(3)) compared to SF (29.9+/-3.7 cm(3)), however, resulted in enhanced destruction of hepatocyte nuclear morphology (DF-score: 2.4+/-0.2 versus SF-score: 1.1+/-0.3; p<0.05) and attenuated leukocyte infiltration within the margin of the cryolesion (DF-score: 1.5+/-0.2 versus SF-score: 2.8+/-0.1; p<0.05). VO-SF was also effective to significantly enhance destruction of hepatocyte nuclear morphology (2.8+/-0.1; p<0.05 versus SF), but, additionally, markedly increased the volume of the cryolesions (43.3+/-5.3 cm(3); p<0.05 versus SF and DF). Interestingly, VO-SF further increased the number of apoptotic cells, while leukocyte infiltration (2.3+/-0.3) was not affected compared to that after SF-treatment. Thus, our data indicate that both DF and VO-SF are effective to enhance parenchymal cell destruction within the margin of the cryolesion. VO-SF additionally increases the volume of the lesion and may therefore be most attractive for successful clinical application.
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Affiliation(s)
- Otto Kollmar
- Department of General, Visceral and Vascular Surgery, D-66421 Homburg/Saar, Germany.
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Jungraithmayr W, Szarzynski M, Neeff H, Haberstroh J, Kirste G, Schmitt-Graeff A, Farthmann EH, Eggstein S. Significance of total vascular exclusion for hepatic cryotherapy: an experimental study. J Surg Res 2004; 116:32-41. [PMID: 14732347 DOI: 10.1016/s0022-4804(03)00054-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND In the liver, efficacy of cryosurgical ablation of tumors located near the retrohepatic vena cava is impaired by the heat-sink effect. This could be overcome by total vascular exclusion (TVE) of the liver. In this study, the effect of TVE on cryosurgical ablation of liver tissue close to the retrohepatic vena cava was investigated with regard to the extent of the cryolesion and complications arising from necrosis of the caval wall. METHODS Of a total of 28 pigs, 14 underwent cryotherapy with TVE compared to 14 without TVE, both involving the vena cava. 7 animals in each group were subjected to one freeze cycle and 7 in each group to two freeze cycles. Temperatures in the cryolesion were monitored and cryolesions were documented sonographically. Laboratory parameters were determined pre- and postoperatively. Follow-up was 14 days. Morphology, extent of the cryolesion, damage to the vena cava and complications were assessed after autopsy. RESULTS With TVE, freezing rates were increased and cryolesions were significantly larger than without TVE. Transmural necroses of the vena cava with complete necrosis of the intima occurred significantly more frequently after TVE. Macro- and microscopically, the damage to the caval wall was considerably more marked after cryotherapy under TVE but in all cases the continuity of the vessel wall remained intact. There were no ruptures, thrombosis, or strictures of the vena cava. CONCLUSIONS The combination of cryotherapy and TVE increases the effectiveness of cryoablation in the liver involving the retrohepatic vena cava without any severe vascular complications occurring in the pig.
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Affiliation(s)
- W Jungraithmayr
- Department of General Surgery, University of Freiburg, Freiburg, Germany.
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Qian GJ, Chen H, Wu MC. Percutaneous cryoablation in treatment of liver cancer: a report of 31 cases. Shijie Huaren Xiaohua Zazhi 2003; 11:712-715. [DOI: 10.11569/wcjd.v11.i6.712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To describe the indication, efficacy and clinical significance of percutaneous cryoablation in the treatment of liver malignancy.
METHODS Total 31 patients with histologically or clinically confirmed primary or metastatic malignancies were treated pucutaneously under ultrasound guidance using the cryocare surgical system from July 2001 to January 2002. All patients were followed up to determine the serum tumor marker, and reveal CT scans, MRI images or utra-sound images.
RESULTS This therapy was performed in 31 patients including 26 cases with Child A liver reserve, 4 cases with Child B and 1 cases with Child C. There were 21 cases of primary liver cancer and 10 metastastic liver cancer. AFP positive small liver cancer became AFP negative in 80% patients. The rate of completely concreted necrosis in small hepatic cancer with negative AFP was 66.7%, shown by CT or MRI. The curative rate for metastasis liver cancer was 50% at CT, MRI or tumor marker level.
CONCLUSION Percutaneous cryoablation is a kind of new palliative treatment for liver carcinoma. It is minimally invasive, safe and effective especially for patients with unresectable liver cancer.
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Affiliation(s)
- Guo-Jun Qian
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Han Chen
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Meng-Chao Wu
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
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Khairy P, Chauvet P, Lehmann J, Lambert J, Macle L, Tanguay JF, Sirois MG, Santoianni D, Dubuc M. Lower incidence of thrombus formation with cryoenergy versus radiofrequency catheter ablation. Circulation 2003; 107:2045-50. [PMID: 12668527 DOI: 10.1161/01.cir.0000058706.82623.a1] [Citation(s) in RCA: 362] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Radiofrequency (RF) catheter ablation is limited by thromboembolic complications. The objective of this study was to compare the incidence and characteristics of thrombi complicating RF and cryoenergy ablation, a novel technology for the catheter-based treatment of arrhythmias. METHODS AND RESULTS Ablation lesions (n=197) were performed in 22 mongrel dogs at right atrial, right ventricular, and left ventricular sites preselected by a randomized factorial design devised to compare RF ablation with cryocatheter configurations of varying sizes (7F and 9F), cooling rates (-1 degrees C/s, -5 degrees C/s, and -20 degrees C/s) and target temperatures (-55 degrees C and -75 degrees C). Animals were pretreated with acetylsalicylic acid and received intraprocedural intravenous unfractionated heparin. Seven days after ablation, the incidence of thrombus formation was significantly higher with RF than with cryoablation (75.8% versus 30.1%, P=0.0005). In a multiple regression model, RF energy remained an independent predictor of thrombus formation compared with cryoenergy (OR, 5.6; 95% CI, 1.7, 18.1; P=0.0042). Thrombus volume was also significantly greater with RF than with cryoablation (median, 2.8 versus 0.0 mm3; P<0.0001). More voluminous thrombi were associated with larger RF lesions, but cryolesion dimensions were not predictive of thrombus size. CONCLUSIONS RF energy is significantly more thrombogenic than cryoenergy, with a higher incidence of thrombus formation and larger thrombus volumes. The extent of hyperthermic tissue injury is positively correlated with thrombus bulk, whereas cryoenergy lesion size does not predict thrombus volume, most likely reflecting intact tissue ultrastructure with endothelial cell preservation.
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Affiliation(s)
- Paul Khairy
- Department of Electrophysiology, Montreal Heart Institute, Quebec, Canada
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Poon RTP, Fan ST, Tsang FHF, Wong J. Locoregional therapies for hepatocellular carcinoma: a critical review from the surgeon's perspective. Ann Surg 2002; 235:466-86. [PMID: 11923602 PMCID: PMC1422461 DOI: 10.1097/00000658-200204000-00004] [Citation(s) in RCA: 308] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE This article reviews the current results of various locoregional therapies for hepatocellular carcinoma (HCC), with special reference to the implications for surgeons. SUMMARY BACKGROUND DATA Resection or transplantation is the treatment of choice for HCC, but most patients are not suitable candidates. The past decade has witnessed the development of a variety of locoregional therapies for HCC. Surgeons are faced with the challenge of adopting these therapies in the management of patients with resectable or unresectable HCC. METHODS A review of relevant English-language articles was undertaken based on a Medline search from January 1990 to August 2001. RESULTS Retrospective studies suggested that transarterial chemoembolization is an effective treatment for inoperable HCC, but its perceived benefit for survival has not been substantiated in randomized trials, presumably because its antitumor effect is offset by its adverse effect on liver function. Nonetheless, it remains a widely used palliative treatment for HCC not amenable to resection or ablative therapies, and it also plays an important role as a treatment of postresection recurrence and as a pretransplant therapy for transplantable HCC. Better patient selection, selective segmental chemoembolization, and treatment repetition tailored to tumor response and patient tolerance may improve its benefit-risk ratio. Transarterial radiotherapy is a less available alternative that produces results similar to those of chemoembolization. Percutaneous ethanol injection has gained wide acceptance as a safe and effective treatment for HCCs 3 cm or smaller. Uncertainty in tumor necrosis limits its potential as a curative treatment, but its repeatability allows treatment of recurrence after ablation or resection of HCC that is crucial to prolongation of survival. Cryotherapy affords a better chance of cure because of predictable necrosis even for HCCs larger than 3 cm, but its use is limited by a high complication rate. There has been recent enthusiasm for heat ablation by microwave, radiofrequency, or laser, which provides predictable necrosis with a low complication rate. Preliminary data indicated that radiofrequency ablation is superior to ethanol injection in the radicality of tumor ablation. The advent of more versatile radiofrequency probes has allowed ablation of HCCs larger than 5 cm. Recent studies have suggested that combined transarterial embolization and heat ablation is a promising strategy for large HCCs. Thus far, no randomized trials comparing various thermoablative therapies have been reported. It is also uncertain whether a percutaneous route, laparoscopy, or open surgery affords the best approach for these therapies. Thermoablative therapies have been combined with resection or used to treat postresection recurrence, and they have also been used as a pretransplant therapy. However, the value of such strategies requires further evaluation. CONCLUSIONS Advances in locoregional therapies have led to a major breakthrough in the management of unresectable HCC, but the exact role of the various modalities needs to be defined by randomized studies. Novel thermoablative techniques provide the surgeon with an exciting opportunity to participate actively in the management of unresectable HCC. Locoregional therapies are also useful adjuncts in the management of patients with resectable or transplantable disease. Hence, surgeons must be equipped with the latest knowledge and techniques of ablative therapy to provide the most appropriate treatment for the wide spectrum of patients with HCC.
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Affiliation(s)
- Ronnie Tung-Ping Poon
- Centre for the Study of Liver Disease & Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong, China.
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Cryosurgical Ablation for the Management of Unresectable Hepatic Colorectal Metastases. COLORECTAL CANCER 2002. [DOI: 10.1007/978-1-59259-160-2_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Gignoux BM, Ducerf C, Mabrut JY, Rivoire M, Rode A, Baulieux J. [Cryosurgery of primary and metastatic cancers of the liver]. ANNALES DE CHIRURGIE 2001; 126:950-9. [PMID: 11803631 DOI: 10.1016/s0003-3944(01)00637-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Cryosurgery is a method of in situ destruction of tissue by a freezing process. Results of hepatic cryosurgery are now available for more than 2100 patients and allow to assess its place in the treatment of hepatic malignancies. Mechanisms of tissue destruction and indications of cryosurgery are detailed. With a peri-operative mortality rate of 1.5%, the safety of hepatic cryosurgery is now admitted. Cryosurgery has its own morbidity: increase of transaminases levels, platelets drop, myoglobinuria and rarely renal failure or cryoshock. In selected patients, hepatic cryosurgery is feasible with a laparoscopic or percutaneous approach. Long term results do not support cryosurgery as an alternative to liver resection. This technique enlarges possibilities of surgical treatment for patients with primary and metastatic liver cancers.
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Affiliation(s)
- B M Gignoux
- Service de chirurgie digestive et de transplantation hépatique, hôpital de la Croix-Rousse, 103, Grande-Rue-de-la-Croix-Rousse, 69317 Lyon, France.
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Mala T, Samset E, Aurdal L, Gladhaug I, Edwin B, Søreide O. Magnetic resonance imaging-estimated three-dimensional temperature distribution in liver cryolesions: a study of cryolesion characteristics assumed necessary for tumor ablation. Cryobiology 2001; 43:268-75. [PMID: 11888220 DOI: 10.1006/cryo.2001.2351] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The goal of this study was to estimate the three-dimensional (3D) temperature distribution in liver cryolesions and assess the margin of the transition zone between the tumoricidal core of the lesion and the surrounding unfrozen tissue, using criteria proposed in the literature. Local recurrences after liver tumor cryoablation are frequent. Temperatures below -40 degrees C and a 1-cm zone of normal tissue included in the cryolesion are considered necessary for adequate ablation. The 3D temperature distribution in 10 pig cryolesions was estimated by numerical solution of a simplified bioheat equation using magnetic resonance imaging data to establish cryolesion border conditions. Volumes encompassed by the -20, -40, and -60 degrees C isotherms were estimated. The shortest distance from every voxel on the -40 degrees C isotherm to the cryolesion edge was calculated and the mean and the maximal of these distances were defined for each cryolesion. Median cryolesion volumes with temperatures of -20, -40, and -60 degrees C or colder were 53, 26, and 14% of the total cryolesion volume, respectively. The median cryolesion volume was 12.3 cm(3). The median of the mean distances calculated between the -40 degrees C isotherm and the cryolesion edge was 4.1 mm and increased with increasing cryolesion volume. The median of the largest of these distances calculated for each cryolesion was 8.1 mm. Temperatures claimed to be adequate for tumor destruction were obtained only in parts of the cryolesion. The adequacy of a 1-cm zone of normal liver tissue included in the cryolesion to ensure tumor ablation is questioned.
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Affiliation(s)
- T Mala
- Interventional Center, The National Hospital, Oslo, Norway.
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Schüder G, Pistorius G, Fehringer M, Feifel G, Menger MD, Vollmar B. Complete shutdown of microvascular perfusion upon hepatic cryothermia is critically dependent on local tissue temperature. Br J Cancer 2000; 82:794-9. [PMID: 10732748 PMCID: PMC2374393 DOI: 10.1054/bjoc.1999.1001] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Since microvascular dysfunction with complete circulatory arrest and, thus, prolongation of tissue ischaemia is considered a potential mechanism for cell necrosis following hepatic cryosurgery, we determined the temperature necessary for induction of complete nutritive perfusion failure in cryothermia-treated rat livers. After localization of the cryoprobe with seven thermocouples and application of a single or double freeze-thaw cycle, in vivo fluorescence microscopy of the cryoinjured left lobe was performed over a 2-h period using a computer-controlled stepping motor, which guaranteed analysis of the identical liver tissue segments with exact allocation of the thermocouples and thus determination of tissue temperature. Cryothermia resulted in a central non-perfused part of injury, surrounded by a heterogeneously perfused peripheral zone. The non-perfused area after single and double freezing continuously increased over the first 90-min period due to a successive shutdown of perfusion within the peripheral border zone. Analysis of the thermocouples' temperature at the end of freezing revealed the 0 degrees C-front at 11.7 mm (single freeze-thaw cycle) and 12.1 mm (double freeze-thaw cycle) distant from the centre of the cryoprobe, which exactly corresponds with the initial (30 min) expansion of the area with nutritive perfusion failure. The increased non-perfused tissue area at 2 h conformed a critical border temperature between 8.29 +/- 1.63 degrees C and 9.07 +/- 0.24 degrees C. From these findings, we conclude that freezing of liver tissue to temperatures of at least < 0 degrees C causes complete/irreversible perfusion failure, which consequently will result in cell death and tissue necrosis, and may thus be supposed as a prerequisite for the safe and successful application of cryosurgery in hepatic tumour ablation.
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Affiliation(s)
- G Schüder
- Department of General Surgery, University of Saarland, Homburg/Saar, Germany
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Ladd AP, Rescorla FJ, Baust JG, Callahan M, Davis M, Grosfeld JL. Cryosurgical Effects on Growing Vessels. Am Surg 1999. [DOI: 10.1177/000313489906500714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Cryosurgical treatment of unresectable hepatic malignancies has proven beneficial in adults. Concerns regarding its use in children include the effect on growth and the risk of injury to adjacent structures. To test the effect of cryoablation on adjacent vascular structures in a growing animal, liquid nitrogen cryoablation was performed on a juvenile murine model. Sprague Dawley rats underwent double freeze-thaw cryoablation of the abdominal aorta with interposed liver tissue. Serial sacrifices were performed over 120 days. Comparisons were made with sham-operated controls. Overall, animal growth paralleled that of sham controls through all time points. Gross examination of aortic diameter also showed similar growth in vessel size between the groups. Histologic analysis demonstrated injury after cryoablation with smooth muscle cell vacuolization, followed by cell death. Aortic media layer collapse resulted from cellular loss, however, elastin fiber composition was maintained. Aortic patency was preserved despite evidence of cellular injury and aortic wall remodeling. An associated thermal sink effect on the opposing wall was identified. After cryoablation adjacent to the abdominal aorta in adolescent rats, vascular patency is maintained and animal growth and structural function is preserved, despite cellular injury and wall compression. These observations suggest that cryoablation may be a useful treatment adjunct in young subjects.
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Affiliation(s)
- Alan P. Ladd
- Section of Pediatric Surgery, Department of Surgery, Indianapolis, Indiana
| | | | - John G. Baust
- Department of Biological Sciences, State University of New York at Binghamton, Binghamton, New York
| | - Michael Callahan
- Section of Pediatric Surgery, Department of Surgery, Indianapolis, Indiana
| | - Mary Davis
- Department of Biological Sciences, State University of New York at Binghamton, Binghamton, New York
| | - Jay L. Grosfeld
- Section of Pediatric Surgery, Department of Surgery, Indianapolis, Indiana
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Heisterkamp J, van Hillegersberg R, Zondervan PE, IJzermans JN. Long-term effects of interstitial laser coagulation in porcine liver with portal inflow occlusion: central versus peripheral lesions. J Vasc Interv Radiol 1999; 10:825-31. [PMID: 10392955 DOI: 10.1016/s1051-0443(99)70122-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
PURPOSE Interstitial laser coagulation (ILC) is an attractive modality for local destruction of unresectable hepatic metastases. Portal inflow occlusion considerably increases its destructive capacity, resulting in lesions 5 cm in diameter; however, effects on adjoining major intrahepatic structures are unknown. Therefore, the purpose of this study was to assess the effects of ILC with portal inflow occlusion on the central portion of the liver as compared to the peripheral portions. MATERIALS AND METHODS ILC was performed in pigs with portal inflow occlusion. Each animal received a single laser application with Nd:YAG light guided simultaneously through four interstitial fibers with 5 W per fiber during 6 minutes. Location of treatment was randomized to either central (n = 8) or peripheral (n = 8). Follow-up was for 1, 2, or 3 months with evaluation of liver functions and weight, as well as macroscopic and microscopic assessment of coagulated lesions and surrounding parenchyma. RESULTS There was no treatment-related morbidity or mortality. No obstructive cholestasis or bile leakage was found. At every moment of evaluation, coagulated volumes in the central group were smaller than in the peripheral lesions (P = .03). Large vessels contiguous to the lesions in the central group were always intact and indications of portal hypertension or thrombosis of hepatic veins were not found. There were no significant differences between the two groups (liver functions [P > or = .15] and weight [P = .69]). CONCLUSION ILC with portal inflow occlusion is a safe technique in the vicinity of vital structures in the liver of healthy pigs. These results justify studies to the feasibility and complication rate of portal inflow occlusion in patients with hepatic malignancies.
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Affiliation(s)
- J Heisterkamp
- Department of Surgery, Erasmus University Rotterdam and University Hospital Rotterdam Dijkzigt, The Netherlands
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Lee FT, Chosy SG, Littrup PJ, Warner TF, Kuhlman JE, Mahvi DM. CT-monitored percutaneous cryoablation in a pig liver model: pilot study. Radiology 1999; 211:687-92. [PMID: 10352592 DOI: 10.1148/radiology.211.3.r99jn29687] [Citation(s) in RCA: 86] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
PURPOSE To determine the safety and feasibility of percutaneous cryoablation with computed tomographic (CT) guidance in a pig liver model. MATERIALS AND METHODS Nine angiographic balloons (mean diameter, 9 mm) were placed in the livers of seven domestic pigs (mean weight, 30.0 kg +/- 14.0 [SD]) as tumor-mimicking lesions. By using ultrasonographic and CT guidance, two 2.4- or 3.0-mm cryoprobes were placed flanking the balloon, and a 15-20-minute freezing process was performed. Hemostasis was achieved by placing absorbable cellulose fabric down the probe tract. After 24-96 hours, animals were sacrificed, and their livers were removed and were sectioned axially at 5-mm intervals for comparison with CT images. RESULTS All animals survived the procedure without complication. No serious hemorrhage was found in any case. Ice balls were readily visualized at CT because they appeared as areas of decreased attenuation (1.0 HU +/- 20.7) when compared with areas of normal liver (48.2 HU +/- 6.3, P < .05). The mean ablative margin was 1.7 cm, and only one of nine cases, the one with probe failure, had a positive margin. Beam-hardening artifact from the metal probes was present but did not interfere with the procedure. Ice-ball size and shape corresponded closely to the area of necrosis determined at histopathologic analysis. CONCLUSION CT-monitored percutaneous cryoablation is feasible and safe in this pig liver model.
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Affiliation(s)
- F T Lee
- Department of Radiology, University of Wisconsin, Madison 53792, USA.
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Kahlenberg MS, Volpe C, Klippenstein DL, Penetrante RB, Petrelli NJ, Rodriguez-Bigas MA. Clinicopathologic effects of cryotherapy on hepatic vessels and bile ducts in a porcine model. Ann Surg Oncol 1998; 5:713-8. [PMID: 9869518 DOI: 10.1007/bf02303482] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The proximity of a hepatic tumor to major vessels and bile ducts limits the use of cryotherapy because of the potential damage to these structures. However, the effects of cryotherapy on major hepatic vessels and bile ducts are not well understood. METHODS Nine pigs underwent laparotomy and intraoperative ultrasound to identify hepatic vessels larger than 5.0 mm. Cryotherapy consisting of two freeze-thaw cycles was performed, incorporating the identified vessel. In four pigs the Pringle maneuver was performed to determine the effects of partial vascular occlusion on the hepatic parenchyma and structures undergoing cryotherapy. The animals were sacrificed 30 days postoperatively, and the livers were processed for histologic examination. RESULTS Eight of the nine livers had vessels larger than 5.0 mm incorporated into the iceball, with all vessels having evidence of infarction but remaining patent. All the livers had major bile ducts incorporated in the iceball, with eight having evidence of infarction. The Pringle maneuver had no real effect on the degree of vessel and bile duct infarction. There was no incidence of hepatic bleeding, liver fracture, bile leak, or hemobilia. CONCLUSIONS Cryotherapy results in the infarction of major hepatic vessels and bile ducts but can be safely performed in the porcine model. Proximity of tumors to major vascular and biliary structures may not be a contraindication to the use of cryotherapy. Further studies are necessary to determine whether cryotherapy can be used in humans.
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Affiliation(s)
- M S Kahlenberg
- Division of Surgical Oncology, Roswell Park Cancer Institute, State University of New York, Buffalo 14263, USA
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Abstract
As 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 degreesC 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.
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Affiliation(s)
- A A Gage
- The Department of Surgery, State University of New York, Buffalo, New York, 14214, USA
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