Efficacy and Safety of Percutaneous Argon-Helium Cryoablation for Hepatocellular Carcinoma Abutting the Diaphragm.

PURPOSE: To evaluate the efficacy and safety of percutaneous argon-helium cryoablation (CA) for hepatocellular carcinoma (HCC) abutting the diaphragm (<5 mm). MATERIALS AND METHODS: A total of 61 consecutive patients (50 men, 11 women; mean age, 56.3 ± 12.1 years old; range, 32-83 years) with 74 HCC tumors (mean size, 3.3 ± 1.7 cm; range, 0.8-7 cm) who were treated with percutaneous argon-helium CA were enrolled in this retrospective study. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events, version 5.0. Local tumor progression (LTP) and overall survival (OS) were analyzed using the Kaplan-Meier method and the log-rank test. The risk factors associated with OS and LTP were evaluated using univariate and multivariate Cox regression analysis. RESULTS: No periprocedural (30-day) deaths occurred. A total of 29 intrathoracic adverse events occurred in 24 of the 61 patients. Major adverse events were reported in 5 patients (pleural effusion requiring catheter drainage in 4 patients and pneumothorax requiring catheter placement in 1 patient). Median follow-up was 18.7 months (range, 2.3-60.0 months). Median time to LTP after CA was 20.9 months (interquartile range [IQR], 14.1-30.6 months). Median times of OS after CA and diagnosis were 27.3 months (IQR, 15.1-45.1 months) and 40.9 months (interquartile range, 24.8-68.6 months), respectively. Independent prognostic factors for OS included tumor location (left lobe vs right lobe; hazard ratio [HR], 2.031; 95% confidence interval [CI], 1.062-3.885; P = .032) and number of intrahepatic tumors (solitary vs multifocal; HR, 2.684; 95% CI, 1.322-5.447; P = .006). Independent prognostic factors for LTP included age (HR, 0.931; 95% CI, 0.900-0.963; P  < .001), guidance modality (ultrasound vs computed tomography and US; HR, 6.156 95% CI, 1.862-20.348; P  =   .003) and origin of liver disease. CONCLUSIONS: Percutaneous argon-helium CA is safe for the treatment of HCC abutting the diaphragm, with acceptable LTP and OS.

Heavy-ion beam mutagenesis of the ectomycorrhizal agaricomycete Tricholoma matsutake that produces the prized mushroom "matsutake" in conifer forests.

Tricholoma matsutake is an ectomycorrhizal agaricomycete that produces the prized mushroom "matsutake" in Pinaceae forests. Currently, there are no available cultivars or cultivation methods that produce fruiting bodies. Heavy-ion beams, which induce mutations through double-stranded DNA breaks, have been used widely for plant breeding. In the present study, we examined whether heavy-ion beams could be useful in isolating T. matsutake mutants. An argon-ion beam gave a suitable lethality curve in relation to irradiation doses, accelerating killing at 100-150 Gy. Argon-ion beam irradiation of the agar plate cultures yielded several transient mutants whose colony morphologies differed from that of the wild-type strain at the first screening, but which did not persist following culture transfer. It also generated a mutant whose phenotype remained stable after repeated culture transfers. The stable pleiotropic mutant not only exhibited a different colony morphology to the wild type, but also showed increased degradation of dye-linked water-insoluble amylose and cellulose substrates. Thus, heavy-ion beams may be useful for isolating mutants of T. matsutake, although precautions may be required to maintain the mutants, without phenotypic reversion, during repetitive culture of their mycelia.

Harmless effects of argon plasma on caudal fin regeneration and embryogenesis of zebrafish: novel biological approaches for safe medical applications of bioplasma.

The argon plasma jet (Ar-PJ) is widely used in medical fields such as dermatology and dentistry, and it is considered a promising tool for cancer therapy. However, the in vivo effects of Ar-PJ for medical uses have not yet been investigated, and there are no biological tools to determine the appropriate clinical dosages of Ar-PJ. In this study, we used the caudal fin and embryo of zebrafish as novel in vivo tools to evaluate the biosafety of Ar-PJ. Typically, Ar-PJ is known to induce cell death in two-dimensional (2D) cell culture systems. By contrast, no detrimental effects of Ar-PJ were shown in our 3D zebrafish systems composed of 2D cells. The Ar-PJ-treated caudal fins grew by an average length of 0.7 mm, similar to the length of the normally regenerating fins. Remarkably, Ar-PJ did not affect the expression patterns of Wnt8a and ß-Catenin, which play important roles in fin regeneration. In the embryo system, 85% of the Ar-PJ-treated embryos hatched, and the lateral length of these embryos was ~3.3 mm, which are equivalent to the lengths of normal embryos. In particular, vasculogenesis, which is the main cellular process during tissue regeneration and embryogenesis, occurred normally under the Ar-PJ dose used in this study. Therefore, our biosafety evaluation tools that use living model systems can be used to provide an experimental guideline to determine the clinically safe dosage of Ar-PJ.

Influence of argon on temperature modulation and neurological outcome in hypothermia treated rats following cardiac arrest.

AIM OF THE STUDY: Combining xenon and mild therapeutic hypothermia (MTH) after cardiac arrest (CA) confers a degree of protection that is greater than either of the two interventions alone. However, xenon is very costly which might preclude a widespread use. We investigated whether the inexpensive gas argon would enhance hypothermia induced neurologic recovery in a similar manner. METHODS: Following nine minutes of CA and three minutes of cardiopulmonary resuscitation 21 male Sprague-Dawley rats were randomized to receive MTH (33°C for 6h), MTH plus argon (70% for 1h), or no treatment. A first day condition score assessed behaviour, motor activity and overall condition. A neurological deficit score (NDS) was calculated daily for seven days following the experiment before the animals were killed and the brains harvested for histopathological analysis. RESULTS: All animals survived. Animals that received MTH alone showed best overall neurologic function. Strikingly, this effect was abolished in the argon-augmented MTH group, where animals showed worse neurologic outcome being significant in the first day condition score and on day one to three and five in the NDS in comparison to MTH treated rats. Results were reflected by the neurohistopathological analysis. CONCLUSION: Our study demonstrates that argon augmented MTH does not improve functional recovery after CA in rats, but may even worsen neurologic function in this model.

One Year Follow-Up Risk Assessment in SKH-1 Mice and Wounds Treated with an Argon Plasma Jet.

Multiple evidence in animal models and in humans suggest a beneficial role of cold physical plasma in wound treatment. Yet, risk assessment studies are important to further foster therapeutic advancement and acceptance of cold plasma in clinics. Accordingly, we investigated the longterm side effects of repetitive plasma treatment over 14 consecutive days in a rodent full-thickness ear wound model. Subsequently, animals were housed for 350 days and sacrificed thereafter. In blood, systemic changes of the proinflammatory cytokines interleukin 1ß and tumor necrosis factor α were absent. Similarly, tumor marker levels of α-fetoprotein and calcitonin remained unchanged. Using quantitative PCR, the expression levels of several cytokines and tumor markers in liver, lung, and skin were found to be similar in the control and treatment group as well. Likewise, histological and immunohistochemical analysis failed to detect abnormal morphological changes and the presence of tumor markers such as carcinoembryonic antigen, α-fetoprotein, or the neighbor of Punc11. Absence of neoplastic lesions was confirmed by non-invasive imaging methods such as anatomical magnetic resonance imaging and positron emission tomography-computed tomography. Our results suggest that the beneficial effects of cold plasma in wound healing come without apparent side effects including tumor formation or chronic inflammation.

Non-thermal dielectric-barrier discharge plasma damages human keratinocytes by inducing oxidative stress.

The aim of this study was to identify the mechanisms through which dielectric-barrier discharge plasma damages human keratinocytes (HaCaT cells) through the induction of oxidative stress. For this purpose, the cells were exposed to surface dielectric-barrier discharge plasma in 70% oxygen and 30% argon. We noted that cell viability was decreased following exposure of the cells to plasma in a time-dependent manner, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The levels of intracellular reactive oxygen species (ROS) were determined using 2',7'-dichlorodihydrofluorescein diacetate and dihydroethidium was used to monitor superoxide anion production. Plasma induced the generation of ROS, including superoxide anions, hydrogen peroxide and hydroxyl radicals. N-acetyl cysteine, which is an antioxidant, prevented the decrease in cell viability caused by exposure to plasma. ROS generated by exposure to plasma resulted in damage to various cellular components, including lipid membrane peroxidation, DNA breaks and protein carbonylation, which was detected by measuring the levels of 8-isoprostane and diphenyl-1-pyrenylphosphine assay, comet assay and protein carbonyl formation. These results suggest that plasma exerts cytotoxic effects by causing oxidative stress-induced damage to cellular components.

Neuroprotection by argon ventilation after perinatal asphyxia: a safety study in newborn piglets.

UNLABELLED: Hypothermia is ineffective in 45% of neonates with hypoxic-ischemic encephalopathy. Xenon has additive neuroprotective properties, but is expensive, and its application complicated. Argon gas is cheaper, easier to apply, and also has neuroprotective properties in experimental settings. The aim was to explore the safety of argon ventilation in newborn piglets. METHODS: Eight newborn piglets (weight 1.4-3.0 kg) were used. Heart rate, blood pressure, regional cerebral saturation, and electrocortical brain activity were measured continuously. All experiments had a 30 min. baseline period, followed by three 60 min. periods of argon ventilation alternated with 30 min argon washout periods. Two animals were ventilated with increasing concentrations of argon (1h 30%, 1 h 50%, and 1 h 80%), two were subjected to 60 min. hypoxia (FiO2 0.08) before commencing 50% argon ventilation, and two animals received hypothermia following hypoxia as well as 50% argon ventilation. Two animals served as home cage controls and were terminated immediately. RESULTS: Argon ventilation did not result in a significant change of heart rate (mean ± s.d. -3.5 ± 3.6 bpm), blood pressure (-0.60 ± 1.11 mmHg), cerebral oxygen saturation (0.3 ± 0.9%), electrocortical brain activity (-0.4 ± 0.7 µV), or blood gas values. Argon ventilation resulted in elevated argon concentrations compared to the home cage controls (34.5, 25.4, and 22.4 vs. 7.3 µl/ml). CONCLUSION: Ventilation with up to 80% argon during normoxia, and 50% argon after hypoxia did not affect heart rate, blood pressure, cerebral saturation and electrocortical brain activity. Clinical safety studies of argon ventilation in humans seem justified.

Is argon plasma coagulation an effective and safe treatment option for patients with chronic radiation proctitis after high doses of radiotherapy? / ¿Es la coagulación con plasma argón una opción terapéutica eficaz y segura en pacientes con proctitis crónica actínica tras dosis altas de radioterapia?

Introduction: In severe cases refractory to medical treatment, APC appears to be the preferred alternative to control persistent rectal bleeding of patients with chronic radiation proctitis. Although successful outcomes have been demonstrated in patients previously treated with moderate doses of radiotherapy, there is reluctance towards its indication due to the concern of severe adverse events in patients treated with high doses of radiation. Objectives: The aim of this study was to assess the efficacy and toxicity of APC in the management of bleeding radiationinduced proctitis in patients treated with high doses of radiation for prostate cancer. Methods and materials: Data from 30 patients were treated with APC due to chronic radiation proctitis, were reviewed retrospectively. All cases had prostate cancer and 9 of them (30 %) underwent previous radical prostatectomy. The median dose of conformal 3D External Beam Radiotherapy (EBRT) delivered was 74 Gy (range 46-76). Median rectal D1cc and D2cc was 72.5 and 72.4 Gy respectively. Median rectal V70, V60 and V40 was 12, 39.5 and 80 %. Cardiovascular and digestive disease, diabetes, smoking behaviour, lowest haemoglobin and transfusion requirements were recorded. Indications for treatment with APC were anemia and persistent bleeding despite medical treatment. Argon gas flow was set at 1.8 l/min with an electrical power setting of 50 W. Results: Median age of all patients was 69.6 years. The median lowest haemoglobin level was 9.6 g/dL. Median time between completion of radiotherapy and first session of APC as 13 months. Ninety-four therapeutic sessions were performed (median 3 sessions). Median time follow-up was 14.5 months (range 2-61). Complete response with resolved rectal bleeding was achieved in 23 patients (77 %), partial response in 5 (16 %) and no control in 2 (6 %). No patients required transfusion following therapy. Two patients developed long-term (> 6 weeks) grade 2 rectal ulceration and grade 2 rectal incontinence, respectively. Conclusions: The argon plasma coagulation is an effective and safe management option in patients with medically refractory rectal bleeding after high doses of radiation for prostate cancer (AU)

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A randomized two-sided placebo-controlled study on the efficacy and safety of atmospheric non-thermal argon plasma for pruritus.

BACKGROUND: To look into new potential indications for physical plasma and because some reports suggest plasma having antipruritic effects, we investigated the treatment of pruritus that often represents a therapeutic challenge. OBJECTIVES: To assess the efficacy and safety of cold atmospheric argon plasma as add-on-therapy in pruritic diseases. METHODS: We treated 46 patients with various pruritic diseases with cold plasma for 2 min daily in addition to standard treatment. All patients served as their own control, when their pruritic disease was treated with argon gas (placebo). The outcome measure was a long-term and short-term reduction in itching measured by means of a visual analogue score (VAS). RESULTS: The VAS scores at baseline were comparable (plasma 4.57, SD 2.38, argon 4.34, SD 2.35). We did not find any significant differences in VAS reduction between plasma and argon: long-term VAS difference of 1.97 (SD 1.33) for plasma and 1.74 (SD 2.37) for argon [P = 0.224, 95% CI: (-0.15; 0.60)], short-term VAS difference of 1.92 (SD 1.33) for plasma and 1.97 (SD 1.29) for argon [P = 0.544, 95% CI: (-0.21; 0.11)]. In both groups, patients experienced a significant reduction of pruritus at the end of therapy compared to baseline [plasma 1.97 (P < 0.0001), placebo 1.74 [P < 0.0001)]. No relevant side effects occurred, and treatment was well tolerated. CONCLUSIONS: Treatment with cold plasma did not result in higher pruritus reduction than treatment with placebo. A significant reduction of pruritus compared to no effect was found at the end of therapy in both groups. Both treatment options had similar safety profiles.

Two cases of suicide by asphyxiation due to helium and argon.

Numerous death cases due to suffocation in a toxic or oxygen deficient gas atmosphere have been described in the literature, but unfortunately especially cases involving inert gases like helium are often presented without detailed toxicological findings. Observations on two suicides are reported, one by helium and the other by argon inhalation. During autopsies gas samples from the lungs were collected directly into headspace vials by a procedure ensuring minimal loss and dilution. Qualitative gas analyses were performed using headspace gas chromatography-mass spectrometry (HS-GC/MS). For carrier gas the commonly used helium was replaced by hydrogen. Qualitative positive results were obtained in the argon case, but the case involving helium revealed negative findings. The use of HS-GC/MS enables in principle to detect inert gases like argon or helium. However, a number of factors may later influence the results as, e.g. a longer period of time between death and sampling or pre-analytical artefacts during sampling of such highly volatile substances. In absence of analytical data supporting helium exposure, the causes of death in the actual cases were found to be asphyxia and in both cases the manner was suicide.

Case report of fatal complication in prostatic cryotherapy. First reported death due to argon gas emboli.

We present the first reported fatality from argon gas emboli during prostate cryosurgery. The decedent underwent cryotherapy for prostate carcinoma using cryoablation probes which were cooled with argon and nitrous oxide and warmed with helium. Minutes into the procedure he experienced sudden cardiovascular collapse and could not be resuscitated. Postmortem examination was performed at the request of family and healthcare providers. Collection of tissues and blood samples had to be conducted carefully to capture suspected noble gases,argon, and helium. Specimens were submitted to Saint Louis University Forensic Toxicology Laboratory for toxicological examination and for evaluation of the composition of the gas retrieved from the vascular system.Gas chromatography mass spectrometric analyses confirmed argon in blood, brain, liver, and gas retrieved from the aorta. These samples had significant argon compared with room air also sent for comparison. The manner of death was accident. To date, there have been no intraoperative surgical fatalities reported from prostatic cryotherapy. We report such an unfortunate death to raise awareness in the medical community. We also describe how to collect and handle blood and tissue samples to submit for toxicological analysis in cases of volatile gas emboli.

The concomitant cryosurgical Cox-Maze procedure using Argon based cryoprobes: 12 month results.

AIM: The cut and sew Cox-Maze III procedure has proven to be extremely effective in curing atrial fibrillation. Due to the relative complexity various procedures were developed to apply ablative lesions to treat atrial fibrillation using different energy sources. In this report we present data related to our experience with Argon based cryoablation system in patients having first time concomitant CryoCox-Maze III procedure and other cardiac surgical procedures. METHODS: This is a prospective study where all patients undergoing the Cox maze procedure are entered into our unique maze registry and are followed at 3, 6, 12, 18, 24 months and yearly thereafter. Health related quality of life (SF-12) and atrial fibrillation frequency and severity of symptoms were obtained preoperatively and at follow up. Rhythm was verified by EKG and 24 hour holter. The Heart Rhythm Society definition of failure (any monitored incident of an atrial arrhythmia >30 seconds) was used to compute the rate of return to sinus rhythm. The ablative technique employed was argon based crytothermia using only 1 to 2 atriotomies. RESULTS: The total number of patients operated by multiple surgeons was 124 with 17% through a right minithoracotomy. The operative mortality (<2%) and perioperative stroke rate (<1%) were very low. At 12 months 87% of the patients were in sinus rhythm and off class I and III antriarrhythmic drugs. There was a clear difference in success rate depending on surgeon's total experience. Quality of life and severity of symptoms were improved significantly. CONCLUSION: The one year results of the CryoCox-Maze III procedure when performed concomitantly with another cardiac surgical procedure demonstrate reasonable safety and efficacy. However, operator experience may be related to better outcome. The ablation of atrial fibrillation may be associated with improved quality of life and symptoms relief.

Argon gas embolism in the application of laparoscopic microwave coagulation therapy.

BACKGROUND: A major concern in the use of the argon beam coagulator system is the potential risk of argon gas embolism. METHODS: Seven cases with argon gas embolism in the English literature were reviewed along with the current case. The latter case was a 77-year-old female having laparoscopic hepatectomy after application of the microwave coagulation system on the cutting planes. RESULTS: Immediately following shots of an argon beam to control local bleeding at the needle hole in the liver caused by microwave coagulation, the end-tidal carbon disappeared, followed by cardiovascular collapse. After 18 min of cardiovascular resuscitation, the tumors were resected under laparotomy. CONCLUSIONS: After reviewing the cases, pneumoperitoneum (57.1%), hepatic needle punctures (42.8%) and direct application of the argon beam to the liver (28.6%) can be considered as risky processes in such events. Caution is necessary in the use of an argon beam in liver surgery to avoid life-threatening gas embolism.

Prospective evaluation of a new high-power argon plasma coagulation system (hp-APC) in therapeutic gastrointestinal endoscopy.

OBJECTIVE: The aim of this study was to prospectively evaluate a new high-power argon plasma coagulation system (hp-APC) in therapeutic gastrointestinal (GI) endoscopy. MATERIAL AND METHODS: From February to June 2005, 216 patients (167 M (77.3%), mean age 66 years) underwent treatment with hp-APC in a total of 275 sessions. Main indications were additive ablation therapy in Barrett's esophagus, palliative treatment of esophageal cancer, gastric polyps/carcinomas, angiodysplasias, Zenker's diverticula, and duodenal adenomas. The new hp-APC device (VIO 300 D with APC 2) was used (15-120 W) in upper GI endoscopy, push-enteroscopy, and double-balloon enteroscopy. RESULTS: The mean number of treatment sessions required was 1.7 (1-5). For palliative tumor ablation in the esophagus, the number of sessions was 2.3 (1-5). Minor complications (pain, dysphagia, neuromuscular irritation, asymptomatic gas accumulation in the intestinal wall) were observed in 29/216 patients (13.4%). Major complications (perforation, stenosis occurred) in 2 patients (0.9%). CONCLUSIONS: Hp-APC appears to be safe and effective in the treatment of various GI condition using different types of endoscopes including double-balloon enteroscopy. Because of the low number of treatment sessions required, hp-APC could be used as an alternative to Nd:YAG laser treatment in tumor debulking.

Correlation between mitotic delay and aberration burden, and their role for the analysis of chromosomal damage.

The aim was to investigate further the relationship between radiation-induced mitotic delay and the expression of chromosome damage in V79 cells. Recently published data on the time-course of chromosome aberrations in V79 first-cycle metaphases after exposure to 10.4 MeV u(-1) Ar ions (LET = 1226 keV microm(-1)) were supplemented and reanalysed. A statistical analysis of the distribution of aberrations among cells was performed. Furthermore, cells were grouped into subpopulations carrying 0, 1 -2, 3-4, 5- 6 and 7 or more aberrations. Then, based on the mitotic index, the flux of each subgroup through the first mitosis was determined and the average entrance time to mitosis was estimated. For comparison, the flux of aberrant V79 cells generated by X-irradiation was analysed. Analysis of the Ar ion data revealed that the flux of each subpopulation through the first mitosis is strongly affected by its aberration burden, i.e. a positive correlation between the mitotic delay and the number of aberrations carried by a cell was observed. The distribution of aberrations among cells could be well described by Neyman-type A statistics; the corresponding fit parameters also reflect the damage-dependent mitotic delay. Interestingly, comparison of the flux of Ar ion and X-ray-irradiated V79 cells through mitosis revealed (1) that a direct correlation exists between the number of aberrations carried by a cell and its average entrance time to mitosis, and (2) that this effect is independent of the linear energy transfer. The role of these observations for radiation cytogenetics is discussed.

Utilização do laser de argônio na remoção de sutura corneana / Use of argon laser in corneal suture removal

OBJETIVO: Descrever a técnica da retirada de sutura em córnea clara, evitando-se o contato da parte externa do fio com o meio intra-ocular e avaliar se esse procedimento evitaria infecções. MÉTODOS: Foi realizado estudo retrospectivo de 1.233 casos de retirada de sutura de mononylon 10.0 em córnea clara, utilizando-se laser de argônio para cortar o fio, no qual se avaliou a incidência de infecções. RESULTADOS: Em 1.071 olhos, um tiro foi suficiente para cortar o ponto. Em 162 olhos, o tiro do laser atingiu a parte epitelial da sutura, sendo necessários disparos extras para cortar a parte intra-estromal e, assim, retirá-la sem que a parte externa do fio passasse pelo interior da córnea. Não ocorreram complicações após a retirada da sutura. CONCLUSÕES: A técnica utilizada mostrou-se eficaz na remoção das suturas e possivelmente apresenta risco menor de infecção, uma vez que a parte do fio sobrejacente ao epitélio não entra em contato com as camadas mais internas da córnea, nem com a câmara anterior, não tendo sido observado nenhum caso de infecção nesta pesquisa.

In vivo characterization of colonic thermal injury caused by argon plasma coagulation.

BACKGROUND: Argon plasma coagulation has been rapidly accepted for endoscopic obliteration of vascular lesions and superficial tumors. Depth of injury is thought to be limited through preferential discharge of energy to nondesiccated tissue. However, argon plasma coagulation-induced injury has not been well characterized. The aim of this study was to characterize argon plasma coagulation-induced colonic injury by using a porcine model. METHODS: Laparotomy was performed in 6 female swine and the colon exteriorized with the subjects under general anesthesia. Lesions were made with an argon plasma coagulation probe held perpendicular and 2 mm from the mucosa. Variables studied were as follows: power (45 W, 60 W, and 75 W) and duration (1, 2, or 3 seconds; n = 11 for each power/duration combination). Injury was graded as either superficial or deep, involving the muscularis propria. RESULTS: Circular muscle layer injury correlated closely with power (p = 0.02), duration (p = 0.001), and total energy delivered (r = 0.977). Longitudinal muscle damage was associated with duration of burn (p = 0.001) and total energy delivered (r = 0.855), but correlated poorly with power (p = 0.40). No perforations occurred. Submucosal injection of saline solution had a protective effect with reductions in circular (90% to 10%, p = 0.002) and longitudinal muscle injury (50% to 0%, p = 0.1). CONCLUSIONS: Injury to the muscularis propria occurs at recommended settings for argon plasma coagulation. Injury correlates with power setting, duration of burn, and total energy delivery. Protective arcing to nondesiccated tissue does not appear to be significant in vivo. Submucosal injection of saline solution protects against deep injury.