CT-Guided Percutaneous Cryoablation in Patients with Lung Nodules Mainly Composed of Ground-Glass Opacities.

PURPOSE: To assess the safety and efficacy of cryoablation in patients with lung nodules mainly composed of ground-glass opacities (GGOs). MATERIALS AND METHODS: In this retrospective study, 50 patients (mean age, 65.0 years ± 12.3; 28 women) with a diagnosis of lung GGO nodules who underwent cryoablation were included (from June 2016 to June 2021). The local recurrence rate, incidence of regional metastases to lymph nodes, incidence of distant metastases, adverse events, and lung function condition were analyzed. RESULTS: Follow-up computed tomography (CT) was performed at a mean of 33 months (range, 3-60 months) after the cryoablation procedure. Outcomes were only evaluated in 30 patients. A total of 20 patients were excluded. Of these 20 patients, 10 patients had no cancer detected by histopathological analysis and a diagnosis was made using CT or positron emission tomography (PET)-CT, The other 10 patients had nodules with a diameter of <10 mm and a consolidation-to-tumor ratio of >0.25; thus, histopathological analysis was not performed because of the small nodule size, and patients were diagnosed using CT or PET-CT. The local recurrence rate was 0% (0 of 30). Evidence of regional metastases of lymph nodes was not found in any patients (0%; 0 of 30), and the incidence of distant metastases was 0% (0 of 30). No major adverse events were noted. Lung function recovered to normal within 1 month after cryoablation in all patients. CONCLUSIONS: Cryoablation may serve as a safe and feasible option for the treatment of lung nodules mainly composed of GGOs.

Clinical Safety and Efficacy of Locoregional Therapy Combined with Adoptive Transfer of Allogeneic γδ T Cells for Advanced Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

PURPOSE: To investigate the safety and efficacy of locoregional therapy plus adoptive transfer of allogeneic gamma delta (γδ) T cells for patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: Thirty patients with HCC and 29 patients with ICC were randomly assigned to receive locoregional therapy (HCC, Group A, n = 15; ICC, Group C, n = 15) or locoregional therapy plus γδ T cell therapy (HCC, Group B, n = 15; ICC, Group D, n = 14). Groups A and C only received locoregional ablation (cryoablation or irreversible electroporation), whereas Groups B and D received locoregional therapy followed by adoptive transfer of allogeneic γδ T cells. The primary endpoints were safety, distant progression-free survival (PFS), local PFS, and overall survival (OS). RESULTS: The median distant PFS was significantly longer in the combined treatment groups than the locoregional treatment groups (HCC: 8 vs 4 months, P = .04; ICC: 8 vs 4 months, P = .021). There was no significant difference in local PFS between the 2 treatment modalities. Patients with HCC in the combined treatment group had a longer OS (median OS: 13 vs 8 months, P = .029). However, there was no significant difference in OS in patients with ICC between the 2 treatment modalities (median OS: 9.5 vs 8 months, P = .546). All adverse events were manageable with no significant difference in incidence between groups. CONCLUSIONS: The novel combination of locoregional ablation with adoptive transfer of allogeneic γδ cells was safe, with encouraging clinical efficacy against HCC and ICC.

A developed non-smooth coordinate transformation for general bilateral vibro-impact systems.

Discontinuity and non-smoothness of system displacement and velocity caused by mechanical impact make the related research on dynamics of vibro-impact systems very difficult and complex. For the sake of bypassing the problems resulting from impact to some extent, Zhuravlev and Ivanov coordinate transformations were proposed, which can effectively convert the vibro-impact system to one without impact terms. In this paper, a more direct and universal transformation for general bilateral rigid vibro-impact systems is proposed. It is inspired by the main technique of Ivanov transformation, which makes the trajectories remain continuous in an auxiliary phase space. It can be directly applied to common vibro-impact systems, whether the positions of barriers are symmetrical or the restitution coefficients of barriers on both sides are consistent. In particular, this method can also be applied to the unilateral vibro-impact system. Validity of the proposed methodology is examined by means of case studies.

Astragalus polysaccharide (APS) attenuated PD-L1-mediated immunosuppression via the miR-133a-3p/MSN axis in HCC.

CONTEXT: Astragalus polysaccharide (APS) is a new tumour therapeutic drug, that has an inhibitory effect on a variety of solid tumours. Tumour cell immunosuppression is related to the up-regulation of programmed death ligand 1 (PD-L1). However, whether APS exerts its antitumor effect by regulating PD-L1 remains unclear. OBJECTIVE: To explore whether APS exerts its antineoplastic effect via regulating PD-L1-mediated immunosuppression in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: SMMC-7721 cells were subcutaneous injected into BALB/C mice for HCC model establishment. Mice were intraperitoneally injected with 100, 200 and 400 mg/kg APS for 12 days. Immunohistochemistry (IHC) was performed to assess CD8+ T cells' rate and PD-L1 level in HCC tissues. HCC cells were pre-treated with 0.1, 0.5 and 1 mg/mL APS for 4 h, then were treated with 10 ng/mL IFN-γ 24 h. PD-L1 level and cell apoptosis was detected by flow cytometry. PD-L1 and Moesin (MSN) proteins were measured by western blot. MiR-133a-3p and MSN mRNA levels were assessed by qRT-PCR. The targets of miR-133a-3p were predicted by starBase, and which was verified by dual-luciferase reporter assay. RESULTS: Our findings illustrated that APS dose-dependently inhibited HCC growth tested with IC50 values of 4.2 mg/mL, and IFN-γ-induced PD-L1 expression and attenuated PD-L1-mediated immunosuppression in HCC cells. APS attenuated PD-L1-mediated immunosuppression via miR-133a-3p in HCC cells. Besides, miR-133a-3p targeted to MSN, and MSN inhibited the antitumor effect of APS by maintaining the stability of PD-L1. Moreover, APS attenuated PD-L1-mediated immunosuppression via the miR-133a-3p/MSN axis. CONCLUSIONS: APS attenuated PD-L1-mediated immunosuppression via miR-133a-3p/MSN axis to develop an antitumor effect. APS may be an effective drug for HCC treatment.

Chemotherapy plus concurrent irreversible electroporation improved local tumor control in unresectable hilar cholangiocarcinoma compared with chemotherapy alone.

INTRODUCTION: Unresectable hilar cholangiocarcinoma (UHC) is a malignant tumor and has a poor prognosis. IRE is a novel non-thermal ablative therapy that causes cellular apoptosis via electrical impulses. To compare the curative effect for UHC, chemotherapy plus concurrent IRE and chemotherapy alone were set up. MATERIALS AND METHODS: From July 2015 to May 2019, 47 patients with UHC were analyzed to chemotherapy + IRE group (n = 23) or chemotherapy alone group (n = 24) in this study. Treatment response was assessed with computed tomography (CT) or magnetic resonance imaging (MRI) 1 month after treatment and every 3 months thereafter. Local tumor progression (LTP), time to LTP, overall survival (OS) and procedure-related complications were compared between the two groups. RESULTS: Chemotherapy plus concurrent IRE group showed a tendency toward a decreased rate of LTP (16.7% vs. 39.5%; p = 0.039) and an increased complete response rate (52.2% vs. 12.5%; p = 0.011) compared with chemotherapy alone group. Time to LTP was significantly longer in the chemotherapy plus concurrent IRE group compared to chemotherapy alone group (11.2 months vs. 4.2 months; p = 0.001). Median OS was significantly longer in the chemotherapy plus concurrent IRE group compared to chemotherapy alone group (19.6 months vs. 10.2 months; p = 0.001). CONCLUSIONS: Chemotherapy plus concurrent IRE improved local control and prolonged time to LTP and OS in patients with UHC.

Transient response of the time-delay system excited by Gaussian noise based on complex fractional moments.

In this paper, the transient response of the time-delay system under additive and multiplicative Gaussian white noise is investigated. Based on the approximate transformation method, we convert the time-delay system into an equivalent system without time delay. The one-dimensional Ito stochastic differential equation with respect to the amplitude response is derived by the stochastic averaging method, and Mellin transformation is utilized to transform the related Fokker-Planck-Kolmogorov equation in the real numbers field into a first-order ordinary differential equation (ODE) of complex fractional moments (CFM) in the complex number field. By solving the ODE of CFM, the transient probability density function can be constructed. Numerical methods are used to ascertain the effectiveness of the CFM method, the effects of system parameters on system response and the level of error vary with time as well as noise intensity are investigated. In addition, the CFM method is first implemented to analyze transient bifurcation, and the relation between CFM and bifurcation is discussed for the first time. Furthermore, the imperfect symmetry property appear on the projection map of joint probability density function.

The future of cryoablation: An abscopal effect.

Cryoablation has become a popular modality to treat a variety of malignant tumors in solid organs and soft tissues. In the future, the use of cryoablation should focus on its abscopal effect. The present review discusses the increased immune response triggered by cryoablation alone or by cryoablation combined with immunotherapies, which can improve the immune response and limit immunosuppression. First, cryoablative techniques should be improved to increase the area of necrosis and reduce the area of apoptosis. Second, cryoablation should be combined with immunotherapies, for example, cyclophosphamide, natural killer cells, granulocyte monocyte colony stimulating factor (GM-CSF), cytotoxic T lymphocyte-associated antigen (CTLA)-4, and programmed death receptor 1 (PD)-1 inhibitors. Cryoablation could also be combined with Hydrogen gas molecules, which were shown recently to stimulate peroxisome proliferator activated receptor gamma coactivator (PGC)-1α, thereby promoting mitochondrial function, which might rescue exhausted CD8+ T cells, leading to prolonged progression-free survival and overall survival of patients with advanced colorectal cancer.

Allogenic Natural Killer Cell Immunotherapy Combined with Irreversible Electroporation for Stage IV Hepatocellular Carcinoma: Survival Outcome.

BACKGROUND/AIMS: We evaluated the clinical effectiveness of irreversible electroporation (IRE) in combination with immunotherapy using allogenic natural killer cells (NK) for stage IV hepatocellular carcinoma (HCC). METHODS: The study involved 40 patients with stage IV HCC who were divided equally into two groups: 1) simple IRE; and 2) IRE plus allogenic NK cells (IRE-NK); we mainly assessed the overall survival (OS). RESULTS: The effect of the IRE-NK treatment was synergistic, i.e., not only did it enhance immune function, it also decreased alpha-fetoprotein expression and showed significantly good clinical effectiveness. At the median 7.6-month follow-up (range, 3.8-12.1 months), median OS was higher in the IRE-NK group (10.1 months) than in the IRE group (8.9 months, P = 0.0078). CONCLUSION: IRE combined with allogeneic NK cell immunotherapy significantly increases the median OS of patients with stage IV HCC.

Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer.

BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, resulting in extremely poor 5-year survival. Late diagnosis of PDAC is mainly due to lack of a reliable method of early detection. Carbohydrate antigen (CA) 19-9 is often used as a tumor biomarker in PDAC; however, the test lacks sensitivity and specificity. Therefore, new sensitive and minimally invasive diagnostic tools are required to detect pancreatic cancer. METHODS: Here, we investigated circulating tumor DNA (ctDNA) which contained KRAS-mutated as a potential diagnostic tool for PDAC patients who underwent irreversible electroporation (IRE). We used droplet digital polymerase chain reaction (ddPCR) to detect the expression of KRAS-mutated genes in plasma samples of 65 PDAC patients who underwent IRE. RESULTS: In these 65 cases, ctDNA was detected in 20 (29.2%) samples. The median overall survival (OS) was 11.4 months with ctDNA+ patients and 14.3 months for ctDNA- patients. ctDNA+ patients had a obviously poorer prognosis associated to overall survival (P < 0.001). CONCLUSION: Our results suggested that the existence of ctDNA was a predictor of survival for PDAC patients. Therefore, ctDNA may be a new sensitive biomarker for monitoring treatment outcome in PDAC.

Irreversible electroporation for the treatment of rabbit VX2 breast cancer.

Irreversible electroporation (IRE) is considered predominantly as a non-thermal ablative technique that uses electrical fields to permeabilize cell membranes and lead to cell death. In this study, we evaluated the efficacy of IRE in the rabbit VX2 breast cancer model. Thirty-five female New Zealand white rabbits were inoculated against VX2 breast cancer cells. The rabbits were randomly divided into two groups: a control group of 15 rabbits and an IRE treatment group of 20 rabbits. Treatment and treatment outcome were evaluated by computerized tomography (CT) scan (plain or contrast enhanced), tumor growth curves and pathological examination including H&E, TUNEL, PCNA and CD31 staining. All rabbits in the IRE treatment group experienced successful IRE without obvious complications except for thoracic major muscle injury. A focused, complete and well-defined ablation zone where tumor cells have been thoroughly eradicated was detected by H&E staining, along with increasing TUNEL staining. The expression of PCNA and CD31 was down-regulated at the periphery of the ablation region. As of the last follow-up, 10 rabbits (67%) in IRE group demonstrated disease is under control; 2 rabbits (13%) are in stable condition; 3 rabbits (20%) suffered from disease progression; the remaining 5 rabbits were sacrificed for pathological examination halfway through the study. Overall, the efficacy of IRE was demonstrated by the creation of a complete ablation region, with increased apoptosis in the ablation zone and decreased proliferation and microvessel density of tumor tissue at the periphery. IRE is a promising local treatment for breast cancer.

Irreversible electroporation in the eradication of rabbit VX2 cervical tumors.

The aim of this study was to evaluate the effects of irreversible electroporation (IRE) on the eradication of rabbit VX2 cervical tumors. A VX2 cervical cancer model was first made in 20 New Zealand rabbits. IRE ablation was performed for the cervical cancers of 15 rabbits when the diameter of the tumor was about 1.0-1.5 cm. The control group (n = 5) did not receive IRE ablation. The gross pathology, ultrasound, computed tomography, hematoxylin and eosin, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and proliferating cell nuclear antigen immunohistochemical staining were performed to evaluate the efficacy of IRE on cervical cancer. All the rabbits tolerated the IRE ablation without serious complications. The tumors treated by IRE slightly increased in size during the first two days, but decreased gradually. IRE caused tumor cell death efficiently, mainly through cell apoptosis; however, it did not induce complete tumor ablation in our study. The results suggested that IRE could eradicate rabbit VX2 cervical tumors efficiently. However, the optimal IRE parameters remain to be determined.

Irreversible electroporation of the uterine cervix in a rabbit model.

The aim of this study was to evaluate the effects of irreversible electroporation (IRE) on the uterine cervix in a rabbit model. IRE ablation was performed in the cervices of 48 New Zealand rabbits, with one ablation lesion in each animal. Gross pathology, transmission electron microscopy, hematoxylin and eosin (H&E), Masson's trichrome (MT) stain, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed at pre-set time points (0 h, 12 h, 1 d, 2 d, 4 d, 7 d, 14 d, and 28 d post-IRE). All the rabbits tolerated the IRE ablation without serious complications. IRE caused complete cell death of the ablated cervix via cell apoptosis. However, fast recovery of the cervix was observed from 7 d post-IRE, with the signs of collagen fibers hyperplasia, the disappearance of the necrotic cells and muscle fibers, and regeneration and extension of the cervical epithelium. At 28 d post-IRE, the ablated cervices recovered to almost normal. Our study suggested that IRE might be an efficient and safe technology to treat cervical tumors, without causing serious cervical damage.

Comparison between cryoablation and irreversible electroporation of rabbit livers at a location close to the gallbladder.

BACKGROUND: The ablation of liver tumors located close to the gallbladder is likely to lead to complications. The aim of this article is to compare the safety and efficacy of irreversible electroporation (IRE) and cryoablation in rabbit livers at a location close to the gallbladder. MATERIALS AND METHODS: We performed cryoablation (n = 12) and IRE (n = 12) of the area of the liver close to the gallbladder in 24 New Zealand white rabbits in order to ensure gallbladder damage. Serum aminotransferase and serum bilirubin levels were measured before and after the ablation. Histopathological examination of the ablation zones in the liver and gallbladder was performed on the 7th day after the ablation. RESULT: Seven days after the ablation, all 24 animals were alive. Gallbladder perforation did not occur in the IRE group; only mucosal epithelial necrosis and serous layer edema were found in this group. Gallbladder perforation occurred in four rabbits in the cryoablation group. Serum aminotransferase and serum bilirubin levels obviously increased in both groups by Day 3 and decreased gradually thereafter. The elevation in aminotransferase and bilirubin levels was greater in the cryoablation group than the IRE group. Pathological examination revealed complete necrosis of the liver parenchyma from the ablation center to the gallbladder in both groups, but bile duct and granulation tissue hyperplasia were observed in only the IRE group. Full-thickness gallbladder-wall necrosis was seen in the cryoablation group. CONCLUSIONS: For ablation of the liver area near the gallbladder, IRE is superior to cryoablation, both in terms of safety (no gallbladder perforation in the IRE group) and efficacy (complete necrosis and rapid recovery in the IRE group).

Initial Experience: Alleviation of Pain with Percutaneous CT-Guided Cryoablation for Recurrent Retroperitoneal Soft-Tissue Sarcoma.

PURPOSE: To evaluate the pain-alleviating effect of computed tomography (CT)-guided percutaneous cryoablation for recurrent retroperitoneal soft-tissue sarcomas (RPSs). MATERIALS AND METHODS: Data from 19 men and 20 women (median age, 50.3 y) with recurrent malignant RPS who underwent percutaneous cryoablation were reviewed retrospectively. A total of 50 tumors were treated by cryoablation, including a single tumor in 29 patients, 2 tumors in 9, and 3 tumors in 1. Adverse events and analgesic outcomes were compared as a function of tumor size (< 10 cm and ≥ 10 cm). Efficacy was assessed based on modified Response Evaluation Criteria In Solid Tumors and progression-free survival (PFS). RESULTS: Grade 1/2 adverse events included fever (n = 17), emesis (n = 7), frostbite (n = 5), and local pain (n = 4). The median follow-up period and PFS were 18.5 months (range, 12-42 mo) and 13.4 months ± 6.2, respectively. At the end of follow-up, 13 patients had died and 26 were living. The mean severe local pain scores on pretreatment day 1 and posttreatment days 1, 5, 10, 15, 20, and 25 were 7.49, 7.40, 6.51, 5.81, 5.35, 5.04, and 5.44, respectively, and significant differences versus pretreatment (P < .001) were reported for posttreatment days 5-25. Immediate relief occurred more frequently in the small-tumor group (4 of 7; 57.1%; P = .018), whereas delayed relief occurred more frequently in the large-tumor group (17 of 22; 77.3%; P = .030). CONCLUSIONS: Minimally invasive percutaneous cryoablation improves local pain and is a feasible treatment for recurrent RPSs.

Cryoprotective therapy for huge hepatocellular carcinoma: a study of 14 patients with a single lesion.

Percutaneous cryoablation is a potential cure for hepatocellular carcinoma (HCC). This study reviewed retrospectively clinical data from 14 patients who underwent cryoablation of huge HCC (long diameter >7 cm). The side effects of cryosurgeries and liver function reverse were recorded and compared everyday. All the patients survived cryosurgery and none died before leaving hospital 2 weeks later. Despite liver-protective treatment before cryosurgery, alanine transaminase (ALT) and aspartate transaminase (AST) levels were increased significantly, but returned to preoperative levels 2 weeks post-cryosurgery. Before cryosurgery, mean total bilirubin (T.BIL) and direct bilirubin (D.BIL) levels were normal; 8-10 days after cryosurgery, they increased more than two-fold, but returned to the preoperative level 2 weeks post-cryosurgery. Serum transaminase and bilirubin levels were compared between hepatitis B positive and negative patients. The hepatitis B negative group's AST level increased significantly 1 day post-cryosurgery (mean, 186 U/L) and decreased to the preoperative level at day 14. In the hepatitis B positive group, means transaminase and bilirubin reached peak values at different days post-cryosurgery. Overall, ALT and AST are valuable indicators of liver function impairment following cryosurgery. In patients with hepatitis B virus, close attention to the serum bilirubin level should be paid 8-10 days after cryosurgery. Liver-protective treatment may alleviate liver function impairment caused by cryosurgery of huge HCC.

Comparison of percutaneous cryoablation with microwave ablation in a porcine liver model.

We compared imaging and pathological changes between argon-helium cryosurgical (AH) and microwave (MW) ablation in a porcine liver model. Immediately after ablation, computed tomography (CT) imaging showed that the area affected by MW ablation was considerably greater than that affected by AH ablation; moreover, the surface area of necrotic tissue was considerably greater in the AH group, whereas the depth of the necrotic area was similar. Seven days after ablation, the affected area had not changed much in the AH group, but it had significantly increased in the MW group; similarly, the surface and depth of the necrotic areas had not changed much in the AH group, but they had increased significantly in the MW group. The pathological findings showed similar definitive areas for both groups at both time points. The findings indicated that long time after both therapies, complete tissue necrosis can be achieved, but the extent and depth of necrosis differ: necrosis foci after AH ablation could be predicted by ice ball under CT image, and necrosis foci after MW ablation will increase obviously. MW ablation might therefore be suitable for tumors with a larger volume and simple anatomical structures, and AH ablation might be suitable for tumors with complex anatomical structures or those located near important organs. These two methods could therefore be used in combination in clinical settings, but details of the procedure need to be studied.

Cryotherapy for local recurrent dermatofibrosarcoma protuberans: experience in 19 patients.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive, cutaneous, malignant tumor characterized by a high propensity for local relapse. Wide and deep local excision with reconstructive surgery is the current standard therapy for DFSP, with a local recurrence rate (LRR) of nearly 40%. In this study, we cured 19 patients with local recurrence of DFSP with 39 sessions of percutaneous cryoablation performed between July 2004 and August 2008. The LRRs after one, two and three cryosurgery sessions per patient were 68%, 54% and 0%, respectively. Moreover, the LRR did not differ with tumor location or size. Furthermore, all patients had a progression-free survival of >5 years. Only minor complications such as fever, local edema, mild nerve injury and local pain occurred, and were resolved within 1 week with symptomatic treatment. In our experience, percutaneous cryoablation is a relatively safe and efficient technique for the treatment of local recurrence of DFSPs.

Diagnosis and treatment of coagulopathy following percutaneous cryoablation of liver tumors: experience in 372 patients.

Coagulopathy after liver cryoablation was first reported many years ago; the cause is local platelet trapping and destruction within the margin of the cryolesion. However, the prognosis and therapeutic effects of coagulopathy remain unclear. This study retrospectively reviewed clinical data from 372 patients (525 sessions) who underwent liver cryoablation in our hospital during the past 4.5 years. Small tumors (major diameter < 6 cm) were treated with a single complete ablation; massive tumors (major diameter 6-10 cm or >10 cm) were divided into two or three parts that were dealt with in turn. Platelet counts decreased to an average of (46.12 ± 68.13) × 10(9)/L after each session of cryoablation. The decline was most evident in patients with high pretreatment platelet counts, while those with low pretreatment counts had the highest risk of coagulopathy. Change in platelet count was not correlated with the diameter of the tumor. Slight coagulopathy (platelet count (70-100) × 10(9)/L) can resolve without treatment within 1 week and administration of recombinant human interleukin-11 can assist recovery from severe coagulopathy (platelet count < 70 × 10(9)/L).

Combination percutaneous cryotherapy and iodine-125 seed implantation for unresectable malignant thymoma: experience in 19 patients.

Thymomas are the most common tumors of the mediastinum. These tumors often compress vital mediastinal organs and severely impact the quality of life of thymoma patients. To avoid the side effects of chemoradiotherapy, some patients with unresectable malignant thymomas have opted to undergo cryotherapy in our hospital. We reviewed the cryosurgery, nursing and follow-up records of our hospital for the past 8 years, and evaluated the safety and efficiency of cryotherapy in 19 patients with unresectable malignant thymomas. No severe complications involving the vital organs surrounding the tumor occurred during or after cryosurgery. The most common side effect was pleural effusion, which occurred in 11 patients and healed after drainage within 1 week. Cough, mediastinal and pericardial effusions, pneumothorax, mild fever and chest tightness also occurred and resolved 1 week after symptomatic treatment. Since our patients had high KPS scores and mild myasthenia gravis symptoms before the treatment, myasthenia gravis did not occur after the treatment. The progression-free survival of the patients was 14-29 months (median, 18 months), and did not differ between patients with large tumors and those with small tumors (P = 0.6753). In conclusion, cryotherapy is a safe and efficient method for the treatment of unresectable malignant thymoma.