Cryo Group Research Articles

Adipose-derived stem cells ameliorate erectile dysfunction after cavernous nerve cryoinjury.

Erectile dysfunction is a common complication following cryotherapy for prostate cancer. In this study, we investigated the efficacy of adipose-derived stem cells (ADSC) in improving erectile function in a rat model of cavernous nerve (CN) cryoinjury and the possible mechanisms. Male rats were intracavernous (IC) injected with EdU-labeled ADSC after bilateral CN cryoinjury. Penile tissues were harvested for histology and protein level detection at 1 and 4weeks after ADSC administration. Erectile function was assessed prior to tissue harvest. We found that erectile function was significantly improved after ADSC treatment via promoting nNOS-positive nerve regeneration and cavernous tissue recovery. The expression of cleaved caspase 3 (an apoptotic marker) reduced after ADSC treatment. Although few EdU-labeled ADSCs were visualized within the penis 4weeks after administration, plenty of EdU-labeled ADSCs were found around penile dorsal vessels and nerves 1week after treatment. Furthermore, three neurotrophic factors (NGF, VEGF, and Neurturin) were significantly decreased in Cryo group, and were partially recovered 1week after ADSC injection. These results suggested that IC injection of ADSC resulted in substantial recoveries of erectile function after CN cryoinjury. The effects may be achieved through the elevated level of neurotrophic factors in penile tissue and subsequent neuroregenerative effects.

Topical adapalene in the treatment of plantar warts; randomized comparative open trial in comparison with cryo-therapy.

Background:Various therapeutic modalities, which are available for treating plantar wart, have not been successful every time.Aims:To evaluate topical adapalene under occlusion in the treatment of plantar warts and compare it with cryo-therapy.Materials and Methods:50 patients with 424 plantar warts were included in this single center, two arm, prospective, randomized, control, open study. Patients were allocated randomly into two groups consisting of 25 patients each. Group A patients having 299 plantar warts were treated using adapalene gel 0.1% under occlusion while Group B patients having 125 warts were treated using cryo-therapy. All the patients were evaluated weekly till the clearance of all the warts and the results compared.Result:All the warts of 25 patients of Group A that were treated using adapalene gel 0.1% cleared in 36.71 ± 19.24 (55.95-17.47) days except those in one patient. In Group B, warts in all except one treated by cryo-therapy cleared in 52.17 ± 30.06 (82.23-22.11) days. There were no side effects like scar formation, irritation, erythema, or infections with adapalene group while in the cryo group scar was seen in 2 patients, pain in 24, erythema in 10, and infection in 3 patients.Conclusion:Adapalene gel 0.1% under occlusion is an effective, safe and easy to use treatment for plantar warts and may help clear lesions faster than cryo-therapy.

Relative Therapeutic Efficacy of Phonophoresis and Cryotherapy as Combined Therapy in the Management of Musculoskeletal Injuries

This study was designed to investigate the efficacy of phonophoresis and cryotherapy as combined therapy (double-modality therapy – DMT) in the management of pain among subjects with musculoskeletal injuries (MSIs).Subjects were assigned randomly to one of three groups: DMT group (n=17) received cryotherapy and 15% methyl salicylate phonophoresis, PHONO group (n=14) received 15% methyl salicylate phonophoresis, andCRYO group (n=19) received cryotherapy and ‘sham’ phonophoresis. Ultrasound at an intensity of 1.5 W/cm² and frequency of 1MHz was used to apply methyl salicylate while intermittent cryotherapy was the mode ofapplication. The pre- and post-treatment pain perception scores (PPS) of the patients were assessed using the visual analogue scale (VAS), and the sessions of treatment in all groups were recorded. Treatment was administered on alternate days and subjects in all groups were discharged when they were pain free. In total, 233 treatment sessions were recorded – 61(26.2%) in DMT, 77(33.0%) in PHONO and 95(40.8%) in CRYO group respectively, which indicated no significant difference (P > 0.05). In the DMT, CRYO and PHONO groups, 16, 12 and 7 subjects respectively were pain free after 1 to 5 treatments. The difference in the severity of pain was significant (P < 0.05) in each group post-treatment, which suggests that DMT, phonophoresis and cryotherapy were equally effective. The study has demonstrated the therapeutic efficacy of DMT, but it was not superior to the single treatment protocol of phonophoresis or cryotherapy. It might however, take less treatment sessions to reduce pain among the subjects with the use of DMT compared with other two modalities.KEYWORDS: cryotherapy, double-modality therapy, musculoskeletal injury, phonophoresis, ultrasound

LED therapy or cryotherapy between exercise intervals in Wistar rats: anti-inflammatory and ergogenic effects

The aim of this study was to test, between two bouts of exercise, the effects of light-emitting diode (LED) therapy and cryotherapy regarding muscle damage, inflammation, and performance. Male Wistar rats were allocated in four groups: control, passive recovery (PR), cryotherapy (Cryo), and LED therapy. The animals were submitted to 45min of swimming exercise followed by 25min of recovery and then a second bout of either 45min of exercise (muscle damage analysis) or time to exhaustion (performance). During the rest intervals, the rats were kept in passive rest (PR), submitted to cold water immersion (10min, 10°C) or LED therapy (940nm, 4J/cm(2)) of the gastrocnemius muscle. Blood samples were collected to analyze creatine kinase activity (CK), C-reactive protein (CRP), and leukocyte counts. The soleus muscles were evaluated histologically. Time to exhaustion was recorded during the second bout of exercise. After a second bout of 45min, the results demonstrated leukocytosis in the PR and Cryo groups. Neutrophil counts were increased in all test groups. CK levels were increased in the Cryo group. CRP was increased in PR animals. The PR group presented a high frequency of necrosis, but the LED group had fewer necrotic areas. Edema formation was prevented, and fewer areas of inflammatory cells were observed in the LED group. The time to exhaustion was greater in both the LED and Cryo groups, without differences in CK levels. CRP was decreased in LED animals. We conclude that LED therapy and cryotherapy can improve performance, although LED therapy is more efficient in preventing muscle damage and local and systemic inflammation.

CRYOBALLOON VERSUS RADIOFREQUENCY FOR PULMONARY VEIN RE-ISOLATION AFTER A FAILED INITIAL ABLATION PROCEDURE IN PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATION

Cryoballoon versus Radiofrequency Ablation. Aim: Catheter ablation of paroxysmal atrial fibrillation (PAF) is associated with an important risk of early and late recurrence, necessitating repeat ablation procedures. The aim of this prospective randomized patient-blind study was to compare the efficacy and safety of cryoballoon (Cryo) versus radiofrequency (RF) ablation of PAF after failed initial RF ablation procedure. Methods: Patients with a history of symptomatic PAF after a previous failed first RF ablation procedure were eligible for this study. Patients were randomized to Cryo or RF redo ablation. The primary endpoint of the study was recurrence of atrial tachyarrhythmia, including AF and left atrial flutter/tachycardia, after a second ablation procedure at 1 year of follow-up. All patients were implanted with a cardiac monitor (Reveal XT, Medtronic) to continuously track the cardiac rhythm. Patients with an AF burden (AF%) ≤ 0.5% were considered AF-free (Responders), while those with an AF% > 0.5% were classified as patients with AF recurrences (non-Responders). Results: Eighty patients with AF recurrences after a first RF pulmonary vein isolation (PVI) were randomized to Cryo (N = 40) or to RF (N = 40). Electrical potentials were recorded in 77 mapped PVs (1.9 ± 0.8 per patient) in Cryo Group and 72 PVs (1.7 ± 0.8 per patient) in RF Group (P = 0.62), all of which were targeted. In Cryo group, 68 (88%) of the 77 PVs were re-isolated using only Cryo technique; the remaining 9 PVs were re-isolated using RF. In RF group, all 72 PVs were successfully re-isolated (P = 0.003 vs Cryo). By intention-to-treat, 23 (58%) RF patients were AF-free vs 17 (43%) Cryo patients on no antiarrhythmic drugs at 1 year (P = 0.06). Three patients had temporary phrenic nerve paralysis in the Cryo group; the RF group had no complications. Of the 29 patients who had only Cryo PVI without any RF ablation, 11 (38%) were AF-free vs 20 (59%) of the 34 patients who had RF only (P = 0.021). Conclusion: When patients require a redo pulmonary vein isolation ablation procedure for recurrent PAF, RF appears to be the preferred energy source relative to Cryo. (J Cardiovasc Electrophysiol, Vol. 24, pp. 274-279, March 2013)

Cryoablation compared with radiofrequency ablation and microwave coagulation therapy for the local control of primary hepatocellular carcinoma.

286 Background: Although cryoablation (Cryo) has been advocated as an effective local treatment for hepatocellular carcinoma (HCC), data are lacking regarding its outcomes in comparison with radiofrequency ablation (RFA) and microwave coagulation therapy (MCT). The aim of this study was to clarify the benefits and disadvantages of each modality for primary HCC. Methods: We reviewed outcomes of 120 patients with primary HCCs (< 5cm) who underwent local treatment (Cryo: n = 55 and RFA/MCT: n = 65) between 1998 and 2011. The primary endpoint was local recurrence free survival (LRFS). The secondary endpoints were complication rates and the length of hospital stay. Results: Age, sex, Child-Pugh score, and background liver disease were identical between both groups. The Cryo group had larger tumors (mean ± standard error tumor size: Cryo 2.55 ± 0.75 cm vs. RFA/MCT 1.96 ± 0.72cm, p < 0.001). The LRFS was higher in the Cryo group than in RFA/MCT group (2270.0 ± 240.8 days vs. 1940.7 ± 269.5 days: p = 0.116). The Cox proportional hazards multivariate analysis revealed that Cryo as the treatment of choice was an independent predictive indicator of improved LRFS (HR, 0.403 [95% CI: 0.202−0.807], P = 0.010). On the contrary, tumor size (for each 1 cm increase, HR, 1.635 [95% CI: 1.038–2.574], p = 0.034) and Child-Pugh score ≥ 6 (HR, 2.166 [95% CI: 1.179 – 3.979], p = 0.013) were negative prognostic factors for LRFS. Subgroup analysis showed that the LRFS for tumors ≤ 2 cm was similar between the 2 groups. However, if the tumor size was greater than 2 cm, the LRFS of the Cryo group was superior to RFA/MCT (2400.0 ± 287.4 days vs. 1177.9 ± 366.5 days: p = 0.004). The complication rates (Cryo 10.9% vs. RFA/MCT 10.8%: p = 0.980) and the length of hospital stay (9.45 ± 5.33 days vs. 9.52 ± 5.90 days: p = 0.947) were similar in both groups. No mortality was observed in the entire cohort. Conclusions: Cryo provides significantly higher chance of local control for primary HCCs compared with RFA/MCT, particularly if the tumor size exceeds 2 cm. Associated risks are at least equivalent to those of RFA/MCT even in patients with marginal to poor liver function. Cryo is a promising local ablative option in an era of rising incidence of HCC.

Cryoballoon Versus Radiofrequency for Pulmonary Vein Re‐Isolation After a Failed Initial Ablation Procedure in Patients with Paroxysmal Atrial Fibrillation

Catheter ablation of paroxysmal atrial fibrillation (PAF) is associated with an important risk of early and late recurrence, necessitating repeat ablation procedures. The aim of this prospective randomized patient-blind study was to compare the efficacy and safety of cryoballoon (Cryo) versus radiofrequency (RF) ablation of PAF after failed initial RF ablation procedure. Patients with a history of symptomatic PAF after a previous failed first RF ablation procedure were eligible for this study. Patients were randomized to Cryo or RF redo ablation. The primary endpoint of the study was recurrence of atrial tachyarrhythmia, including AF and left atrial flutter/tachycardia, after a second ablation procedure at 1 year of follow-up. All patients were implanted with a cardiac monitor (Reveal XT, Medtronic) to continuously track the cardiac rhythm. Patients with an AF burden (AF%) ≤ 0.5% were considered AF-free (Responders), while those with an AF% > 0.5% were classified as patients with AF recurrences (non-Responders). Eighty patients with AF recurrences after a first RF pulmonary vein isolation (PVI) were randomized to Cryo (N = 40) or to RF (N = 40). Electrical potentials were recorded in 77 mapped PVs (1.9 ± 0.8 per patient) in Cryo Group and 72 PVs (1.7 ± 0.8 per patient) in RF Group (P = 0.62), all of which were targeted. In Cryo group, 68 (88%) of the 77 PVs were re-isolated using only Cryo technique; the remaining 9 PVs were re-isolated using RF. In RF group, all 72 PVs were successfully re-isolated (P = 0.003 vs Cryo). By intention-to-treat, 23 (58%) RF patients were AF-free vs 17 (43%) Cryo patients on no antiarrhythmic drugs at 1 year (P = 0.06). Three patients had temporary phrenic nerve paralysis in the Cryo group; the RF group had no complications. Of the 29 patients who had only Cryo PVI without any RF ablation, 11 (38%) were AF-free vs 20 (59%) of the 34 patients who had RF only (P = 0.021). When patients require a redo pulmonary vein isolation ablation procedure for recurrent PAF, RF appears to be the preferred energy source relative to Cryo.

Cryothermal vs. radiofrequency ablation as atrial flutter therapy: a randomized comparison

Radiofrequency (RF) ablation of the cavotricuspid isthmus (CTI) is an effective treatment for atrial flutter (AFL). However, RF may injure cardiac structures such as the atrio-ventricular node or the right coronary artery and is usually painful. This prospective, randomized study compares cryoablation (Cryo) with RF ablation regarding efficacy, safety, and perceived pain. One-hundred and fifty-three patients (78 Cryo; 75 RF) with CTI-dependent AFL--median age 65 years (range 34-82), 140 men (91%)--were randomized to Cryo or RF. Primary endpoint was demonstration of long-term efficacy defined as no symptomatic recurrence of AFL at the 6-month follow-up. Radiofrequency ablation was performed with a 3.5 mm open-irrigated-tip catheter and Cryo with a 9 F, 8 mm tip catheter. Ablation endpoint was bidirectional CTI block. Pain was evaluated with a visual analogue scale (VAS; 0-10). The acute success rate was 92% for Cryo and 95% for RF (P = 0.58). Procedural time was longer in the Cryo group (152 ± 54 min) than the RF group (116 ± 41 min) (P < 0.001). Cryoablation was considerably less painful compared with RF (mean VAS-Cryo 0.7 ± 1.2 vs. VAS-RF 4.6 ± 2.0; P < 0.001). Success rate at 6-month follow-up was 93% (73 of 78) for Cryo and 97% (73 of 75) for RF (P = 0.86). No major adverse events occurred in any group. Cryoablation of isthmus-dependent AFL is not inferior to RF but with significantly less procedure-related pain.

Production of Consistent Pain by Intermittent Infusion of Sterile 5% Hypertonic Saline, Followed by Decrease of Pain With Cryotherapy

It is suggested that postinjury pain is difficult to examine; thus, investigators have developed experimental pain models. To minimize pain, cryotherapy (cryo) is applied, but reports on its effectiveness are limited. To investigate a pain model for the anterior knee and examine cryo in reducing the pain. Controlled laboratory study. Therapeutic modality laboratory. 30 physically active healthy male subjects who were free from any lower extremity orthopedic, neurological, cardiovascular, or endocrine pathologies. Perceived pain was measured every minute. Surface temperature was also assessed in the center of the patella and the popliteal fossa. There was a significant interaction between group and time (F68,864 = 3.0, P = .0001). At the first minute, there was no difference in pain between the 3 groups (saline/cryo = 4.80 ± 4.87 mm, saline/sham = 2.80 ± 3.55 mm, no saline/cryo = 4.00 ± 3.33 mm). During the first 5 min, pain increased from 4.80 ± 4.87 to 45.90 ± 21.17 mm in the saline/cryo group and from 2.80 ± 3.55 to 31.10 ± 20.25 mm in the saline/sham group. Pain did not change within the no-saline/cryo group, 4.00 ± 3.33 to 1.70 ± 1.70 mm. Pain for the saline/sham group remained constant for 17 min. Cryo decreased pain for 16 min in the saline/cryo group. There was no difference in preapplication surface temperature between or within each group. No change in temperature occurred within the saline/sham. Cooling and rewarming were similar in both cryo groups. Ambient temperature fluctuated less than 1°C during data collection. Intermittent infusion of sterile 5% hypertonic saline may be a useful experimental pain model in establishing a constant level of pain in a controlled laboratory setting. Cryotherapy decreased the induced anterior knee pain for 16 min.

Cryoablation during left ventricular assist device implantation reduces postoperative ventricular tachyarrhythmias

The number of patients undergoing implantation of a HeartMate II left ventricular assist device (LVAD; Thoratec Corporation, Pleasanton, Calif) is rising. Ventricular tachyarrhythmia (VA) after placement of the device is common, especially among patients with preoperative VA. We sought to determine whether intraoperative cryoablation in select patients reduces the incidence of postoperative VA. From January 2009 through September 2010, 50 consecutive patients undergoing implantation of the HeartMate II LVAD were examined. Fourteen of these patients had recurrent preoperative VA. Of those patients with recurrent VA, half underwent intraoperative cryoablation (Cryo: n=7) and half did not (NoCryo: n=7). Intraoperatively, patients underwent localized epicardial and endocardial cryoablation via LVAD ventriculotomy. Cryothermal lesions were created to connect scar to fixed anatomic borders in the region of clinical VA. Demographics, risk factors, intraoperative features, and outcomes were analyzed to investigate the feasibility of cryoablation. Thirty-day mortality remained low (n=1, 2%) among all LVAD recipients. There were no differences in risk factors between groups except that preoperative inotropes were less prevalent in Cryo patients (P=.09). Compared with NoCryo, the Cryo group had significantly decreased postoperative resource use and complications (P<.05). Recurrent postoperative VA did not develop in any of the Cryo patients (P=.02). Postoperative VA can be minimized by preoperative risk assessment and intraoperative treatment. Localized cryoablation in select patients offers promising early feasibility when performed during HeartMate II LVAD implantation. Further prospective analysis is required to investigate this novel approach.

The clinical application of cryoplasty for lower extremity arterial occlusive disease

Objective To observe the short term efficacy and safety of cryoplasty in treatment of lower extremity arterial occlusive disease. Methods Twenty five patients (27 limbs) scheduled for lower extremity artery balloon angioplasty were randomized to cryoplasty [ group CRYO, 10 patients with 8 male,age ( 76 ± 8 ) years]or conventional balloon angioplasty [ group COBA, 15 patients with 13 male, age ( 68 ±4) years], In CRYO group, the average lesion length and stenosis were (6.7 ±0.9) cm and, (91 ±6)％, respectively. The average ankle-brachial index (ABI) was 0. 46 ±0. 07 before treatment. According to Fontaine clinical stages, 7 patients (7/10) in this group were staged Ⅱ and the other 3 (3/10) were staged Ⅲ. According to Trans Atlantic Inter Society Consensus (TASC), 8 patients (8/10) were classified as TASC type A and the other 2 (2/10) were TASC type B. In COBA group, the average lesion length and stenosis were (6. 5 ± 0. 7 ) cm and ( 89 ± 7 ) ％, respectively. The average ABI was 0. 48 ± 0. 08 before treatment. According to Fontaine clinical stages, 13 patients (13/15) were staged Ⅱ and the other 2(2/15) were staged Ⅲ. And, according to TACS, 13 patients (13/15) were classified as TASC type A and the other 2 (2/15) were TASC type B. The clinical symptoms and signs had no significant difference between the two groups ( P ＞ 0. 05 ). Clinical status was evaluated according to Rutherford classification.The clinical efficacy on the 2nd and 30 th day after the operation was compared using analysis of variance with repeated measurements. Results Technical success was achieved in all patients both in CRYO group (10/10) and in COBA group (15/15). None patient in CRYO group occurred postoperative complication.One patient in COBA group ( 1/15 ) occurred vessel wall dissection. In CRYO group, clinical status were remarkably improved in 8 patients (8/10) and moderately improved in 2 patients (2/10) ; while, in COBA group, they were remarkably improved in 13 patients ( 13/15 ) and moderately improved in 2 patients ( 2/15 ). The average ABI was 0. 84 ± 0. 04 in group CRYO and 0. 84 ± O. 05 in group COBA ( P ＝ 0. 20).The average stenosis was (29 ± 4) ％ in group CRYO and (32 ± 4) ％ in group COBA ( P ＝ 0. 55 ). No significant difference was detected between the two groups. Both the average ABI and stenosis presented statistically significant difference between pre-operation and post-operation in both groups ( P ＜ 0. 01,respectively). Conclusions Cryoplasty is safe for the treatment of lower extremity arterial occlusive disease, which showed a good short-term result in this research. Key words: Angioplasty, balloon; Hypothermia; Arterial occlusive disease; Lower extremity

584 Silent cerebral thromboembolic lesions on MRI following atrial fibrillation ablation with different technologies

584 Silent cerebral thromboembolic lesions on MRI following atrial fibrillation ablation with different technologies

The effect of slow-freeze versus vitrification on the oocyte: an animal model

The goal of this study was to determine whether there is a deleterious effect on dynamic events in the nucleus and cytoplasm of oocytes in an animal model. Prospective experimental study. Bovine oocytes were matured in media supplemented with 75mIU/ml of a gonadotropins in vitro for 24 h and randomly frozen by either slow-freezing, SF, or vitrification with DMSO(V1) or vitrification with PROH(V2). Fresh oocytes comprised the control group(CL). Nuclear maturation status, spindle and chromosomal configurations, dynamic changes of the cortical granules(CGs) and mitochondria were evaluated by immunostaining and confocal laser scanning microscope. After thawing/warming, mitochondria formed larger clusters and migrated more centrally in all three cryo groups; CGs became more dispersed in the cytoplasm. Significant reduction in normal spindle and chromosomal configurations, was observed in all three cryo-groups as compared with CL. Global DNA methylation levels were significantly reduced in SF and V1 groups as compared to CL; however, methylation levels were significantly increased in the V2. Proportion of severely apoptotic oocytes was dramatically increased in all three cryo-groups, compared with CL.Table 1Dynamic changes of cytoplasm and nucleus of oocytes from slow-freeze and vitrificationParametersCLSFV1V2Dispersed CGs (%)35.6 ± 4.136.5 ± 4.246.7 ± 5.7∗P<0.0532.1 ± 9.0Clustered Mt(%)40.5 ± 5.373.0 ± 12.3P<0.01 (vs. Fresh).56.2 ± 7.9∗P<0.0552.6 ± 7.3∗P<0.05Normal Spindle (%)73.4 ± 7.655.7 ± 6.2P<0.01 (vs. Fresh).51.7 ± 7.9P<0.01 (vs. Fresh).39.3 ± 7.9P<0.01 (vs. Fresh).DNA Methylation (density)7.1 ± 0.54.6 ± 0.5P<0.01 (vs. Fresh).2.7 ± 0.3P<0.01 (vs. Fresh).11.4 ± 0.7P<0.01 (vs. Fresh).Oocyte Apoptosis (%)9.6 ± 0.624.1 ± 5.8P<0.01 (vs. Fresh).32.8 ± 5.8P<0.01 (vs. Fresh).44.1 ± 4.0P<0.01 (vs. Fresh).∗ P<0.05∗∗ P<0.01 (vs. Fresh). Open table in a new tab Overall, results demonstrate V1 is better in preserving cellular and nuclear integrity of the oocyte. V2 method makes the oocyte more vulnerable to increased DNA methylation, which is associated with imprinting disorders. In summary, V1 is recommended as the superior method to cryo-preserve oocytes clinically.

Longterm effects of cardiac mediastinal nerve cryoablation on neural inducibility of atrial fibrillation in canines

In canines, excessive activation of select mediastinal nerve inputs to the intrinsic cardiac nervous system induces atrial fibrillation (AF). Since ablation of neural elements is proposed as an adjunct to circumferential pulmonary vein ablation for AF, we investigated the short and long-term effects of mediastinal nerve ablation on AF inducibility. Under general anesthesia, in 11 dogs several mediastinal nerve sites were identified on the superior vena cava that, when stimulated electrically during the atrial refractory period, reproducibly initiated AF. Cryoablation of one nerve site was then performed and inducibility retested early (1–2 months post Cryo; n = 7) or late (4 months post Cryo; n = 4). Four additional dogs that underwent a sham procedure were retested 1 to 2 months post-surgery. Stimulation induced AF at 91% of nerve sites tested in control versus 21% nerve sites early and 54% late post-ablation (both P < 0.05). Fewer stimuli were required to induce AF in controls versus the Early Cryo group; this capacity returned to normal values in the Late Cryo group. AF episodes were longer in control versus the Early or Late Cryo groups. Heart rate responses to vagal or stellate ganglion stimulation, as well as to local nicotine infusion into the right coronary artery, were similar in all groups. In conclusion, focal damage to intrinsic cardiac neuronal inputs causes short-term stunning of neuronal inducibility of AF without major loss of overall adrenergic or cholinergic efferent neuronal control. That recovery of AF inducibility occurs rapidly post-surgery indicates the plasticity of intrathoracic neuronal elements to focal injury.

135 Combined radiofrequency and cryoablation for paroxysmal atrial fibrillation. A novel technique to reduce recurrences: Abstract 135 Table 1

<h3>Introduction</h3> We hypothesised that electrical isolation of the pulmonary veins (PV) by wide area circumferential ablation with radiofrequency (RFA) followed by selective PV ostial ablation using a cryoablation balloon (Cryo) would create parallel lines of block and reduce the incidence of PV reconnection.This would therefore improve first time success rates for paroxysmal atrial fibrillation (PAF). <h3>Methods</h3> A retrospective study examined 59 consecutive patients undergoing first time PV isolation for symptomatic PAF(&gt;1 year) and had failed at least two medical therapies. Patients received RFA alone, Cryo alone or combined RFA (to isolate PVs) followed by Cryo. Patients were followed up with 12 lead ECG, 7 day Holter monitoring and clinical review. Any atrial arrhythmia lasting greater than 30 s during a 3 month follow-up period was documented as a recurrence. <h3>Results</h3> Significantly fewer patients had symptomatic palpitations (with documented PAF) in the combined group, with a trend towards need for less redo procedures (Abstract 135 table 1). Complications were one phrenic nerve palsy and one haematoma in the Cryo group, one grounding plate burn in the RF group and one phrenic nerve palsy , one pericardial effusion and one haematoma in the combined group. Total procedure time was greater in the combined group (Abstract 135 table 1). <h3>Conclusion</h3> Preliminary results suggest that combination of RF and Cryoablation is superior to either alone. A prospective randomised trial is underway to confirm these findings.

Alternative Energy Sources for Surgical Treatment of Atrial Fibrillation in Patients Undergoing Mitral Valve Surgery: Microwave Ablation vs Cryoablation

The study aim was to compare maze outcomes using microwave ablation or cryoablation in patients with mitral disease and atrial fibrillation (AF). Between 1999 and 2005, 340 patients underwent mitral valve surgery and concomitant maze procedure involving either microwave ablation (n=96, MW group) or cryoablation (n=244, Cryo group). Mean age at operation was 50.0±12.5 yr. Follow-up period was 46.1±28.2 months. The Cryo group showed a longer aortic clamping time than the MW group (P=0.005). There were no differences in operative mortality and morbidity rates. The unadjusted 5-yr AF free rate was 61.3±1.2% in the MW group and 79.9±3.2% in the Cryo group (P=0.089). After adjustment, the MW group only showed a tendency toward more frequent AF recurrence than the Cryo group (Hazard ration 1.66, 95% confidence interval 0.89 to 3.07). Multivariate analysis revealed that older patient age (P<0.001) and greater left atrial size (P<0.001) were independent risk factors for AF recurrence. Although the use of microwave ablation results in shorter aortic clamping time, it has a tendency toward more frequent late AF recurrence than with cryoablation.

Molecular Enhancement of Thermal Ablation Therapies Using TNF-α-Coated Gold Nanoparticles in a Translational Model of Renal Tumors

Thermal ablation therapies are currently used for the treatment of select renal masses. Such treatments are limited to tumors that are small (&lt;3 cm diameter), exophytic, and away from vital structures such as ureter or intestine. Novel treatment approaches are geared towards increasing the size of the thermal lesion created, limiting damage to collateral normal tissues, reducing local recurrence and distant metastases as well as improving the imaging potential of the therapy. Previous studies have demonstrated the enhancement of thermal therapies in pre-clinical murine models of solid tumors by intravenously infusing 33 nm TNF-α and PEG coated gold nanoparticles (CYT-6091, Cytimmune Sciences Inc.) prior to ablation. This study investigates the enhancement of thermal ablation therapy by CYT-6091 in a translational animal model of renal tumors. New Zealand White rabbits (37 for radiofrequency ablation (RFA), 20 for cryoablation) had VX-2 tumors implanted into their bilateral kidneys. The tumors were allowed to grow for 14 days to a size of ∼1 cm. For RFA, the rabbits were split into 3 treatment groups of 10 rabbits each and a sham group of 7 rabbits. The groups were treated with CYT-6091 (200 μg/kg) only, RFA only, or CYT-6091 (200 μg/kg) followed 4 hours later by RFA. For cryoablation, 2 treatment groups of 10 rabbits each were used. The groups were treated with cryoablation only or CYT-6091 (200 μg/kg) followed 4 hours later by cryoablation. The kidneys were harvested 3 days later for RFA and 7 days later for cryoablation. Gross and microscopic measurements of the ablation size as well as histological analysis using H&amp;E staining were performed. The RFA plus CYT-6091 group had a larger zone of complete cell death than the RFA only group when measured both on gross sectioning (0.32±0.03 vs. 0.22±0.07cm3, p=0.015) and on microscopic examination (0.30±0.07 vs. 0.23±0.03cm3, p=0.03). Overall this was a 23% increase in ablation volume. This difference in ablation size was due to a replacement of partially ablated tissue at the periphery in the RFA only group by completely ablated tissue in the RFA plus CYT-6091 group. Thus this zone of partially ablated tissue was smaller in the RFA plus CYT-6091 group than the RFA only group (0.08±0.02cm3 vs. 0.13±0.05cm3, p=0.01). Excessive tumor growth into the ablation lesion at day 7 following cryoablation prevented accurate measurements in these groups; however, a significant decrease in the rate of peritoneal carcinomatosis (metastases) was obtained in the cryo plus CYT-6091 group compared to the cryoablation alone group (1/10 vs. 8/10, p=0.04). We have shown that use of CYT-6091 prior to thermal ablation therapy in a rabbit kidney tumor model can minimize the zone of partial treatment at the periphery of the thermal lesion and thus maximize the complete kill zone in RFA while significantly decreasing the rate of metastases in cryoablation. These data provide preliminary evidence for the efficacy of adjuvant use of CYT-6091 for thermal ablation therapies in a large animal translational tumor model.

A randomized trial of cryo stripping versus conventional stripping of the great saphenous vein

This multicenter randomized clinical trial compared cryo stripping of the great saphenous vein (GSV) with conventional stripping. The study randomized 494 patients with symptomatic (CEAP) clinical severity class 2 to 4 to cryo stripping (n = 249) or conventional stripping (n = 245). The primary outcome was residual GSV 6 months after surgery measured by venous duplex ultrasound imaging. Secondary outcomes were quality of life, operation time, and postoperative neural damage. Duration of follow-up was 6 months. Quality of life was measured at 6 and 26 weeks postoperatively with the Aberdeen Varicose Vein Questionnaire (AVVQ) and Medical Outcomes Study Short-Form 36 (SF-36) Health Survey. The two groups were well matched at baseline. The percentage of patients with residual GSV at 6 months (primary outcome) was 44% (102 of 230) in the cryo group and 15% (33 of 215) in the conventional group (difference 29%; 95% confidence interval [CI], 21%-37%, P < .001). Median operation time was significantly shorter in the cryo group (30 minutes) compared with the conventional group (39 minutes). Neural damage was 12% in both groups, and thus not significantly different. Scores on the subdomains of the SF-36 showed no significant change between the groups. The AVVQ after conventional stripping was 8.0, which was a better result than the 11.7 result after cryo stripping (difference 2.6 points; 95% CI, 1.0-4.2; P = .001, repeated measurements analysis of variance with adjustment for baseline scores). Cryo stripping accounts for numerous procedural failures and hence residual GSV in patients. The AVVQ showed small but significantly better results for patients after a conventional stripping. Cryo stripping has no benefits over conventional stripping.

Neonatal outcome of 937 children born after transfer of cryopreserved embryos obtained by ICSI and IVF and comparison with outcome data of fresh ICSI and IVF cycles

To evaluate the safety of cryopreservation in combination with IVF and ICSI, prenatal diagnosis and neonatal outcome were investigated in children conceived from frozen-thawed ICSI embryos (cryo ICSI) and frozen-thawed IVF embryos (cryo IVF). Data were also compared with earlier published results from fresh ICSI and IVF embryos. Questionnaire data and results of physical examination at 2 months of 547 cryo ICSI children and 390 cryo IVF children were compared, and these were also compared with those of infants born after transfer of fresh embryos. Birth characteristics were comparable for cryo ICSI and cryo IVF infants. Cryo singletons showed a trend towards higher mean birthweight compared with fresh singletons, in ICSI and IVF, reaching significance when all cryo (ICSI plus IVF) singletons were considered. Low birthweight rate according to multiplicity was comparable between the fresh and the cryo groups, in ICSI and IVF. Non-statistically significantly increased rates of de novo chromosomal anomalies (3.2%) were found in cryo ICSI fetuses/children compared with the fresh ICSI group (1.7%) (OR 1.96; 95% CI 0.92-4.14). Major malformations were more frequently observed in cryo ICSI live borns (6.4%) than in cryo IVF live borns (3.1%) (OR 2.15; 95% CI 1.10-4.20) and fresh ICSI live borns (3.4%) (OR 1.96; 95% CI 1.31-2.91). In cryo ICSI compared with cryo IVF, prenatal and neonatal outcome results were comparable, except for a higher major malformation rate in the cryo ICSI group. In the total cryo group compared with the total fresh group, we found a higher mean birthweight in singletons and a higher major malformation rate in live borns.

Prevalence of cryoglobulinemia and autoimmunity markers in renal-transplant patients

To examine the prevalence of cryoglobulinemia (Cryo) and autoimmune markers in renal-transplant recipients in a stable condition, and to determine its risk factors and impact upon allograft function. In May, 2006, 117 kidney-transplant (KT) recipients, aged 31 â 76 years, were tested for cryoglobulinemia, hepatitis B and C, complement C3, C4, CH50, antinuclear (ANAs), anticytoplasmic nuclear (ANCAs) and anticardiolipid antibodies, rheumatoid factor (RF), and lymphocyte subpopulations. Renal, liver, and hematological tests were also performed. Immunosuppressive regimens were based on calcineurin inhibitors (82%). Cryo was positive in 47 patients (Cryo(+): 40.2%), of whom 13 were HCV+ (27.7%), with characteristics of Type II in 21.2% and Type III in 78.8%. Cryo was positive in 13/16 (81.2%) of HCV+/RNA+ patients vs. 34/101 (33.6%, p = 0.0003) of HCV-negative patients. Cryo(+) RT patients had been recipients of a graft for longer (142 months) than Cryo(-) patients, i.e., 95 months (p = 0.02). Creatinine clearances were similar in the two groups (56 vs. 50 ml/mn, p = 0.5), as were microalbuminuria and albuminemia. There was no difference between Cryo(-) and Cryo(+) patients in terms of age, sex, HLA mismatch, daily steroid doses, liver and hematological tests, ANAs, anticardiolipid antibodies, serum complement, and lymphocyte subpopulations. RF occurred in all Cryo(+) patients and in 82.8% of Cryo(-) patients, with higher titers in the Cryo(+) group (23 vs. 9 UI/ml, p = 0.012). ANCA occurred in nine Cryo(-) but in no Cryo(+) patients (p = 0.013). Finally, a multivariate analysis was not able to determine any predictive factor associated with cryoglobulinemia. Cryoglobulinemia is frequent after KT, and is associated with HCV markers, RF, and absence of ANCA.