Advantages and challenges for noninvasive atrial fibrillation ablation.

PURPOSE: Although catheter ablation is an effective therapy for atrial fibrillation (AF), risks remain and improved efficacy is desired. Stereotactic radiotherapy is a well-established therapy used to noninvasively treat malignancies with precision. We sought to evaluate stereotactic arrhythmia radioablation (STAR) as a therapeutic option for treating AF. METHODS AND RESULTS: Three cancer patients with drug refractory AF were enrolled. Planning software using 3-D CT of the left atrium was used to design a desired ablation volume encompassing antral circumferential pulmonary vein isolation, roof and floor lines to create a "box" lesion set. After planning, patients were treated in the radioablation suite. STAR was able to deliver the intended radiation dose to the target in all 3 patients. No complications were observed over a follow-up period of 24 months. One patient with paroxysmal AF died from deterioration of cancer. The autopsy revealed evidence of fibroblasts and fibrogenesis in the region of atrial tissues targeted with radioablation. In one of these patients, left atrial posterior wall electrograms recorded from the esophagus before and 3 months after STAR indicated successful electrical isolation. CONCLUSIONS: This is the first report of non-invasive radioablation of the left atrium with demonstration of successful electrical isolation. Although STAR may be safe and effective in delivering ablative energy to the left atrium, further evaluation is warranted regarding effectiveness.

Log-file analysis of accuracy of beam localization for brain tumor treatment by CyberKnife.

PURPOSE: The CyberKnife system generates log-files including actual treatment parameters for each procedure. In this study, log-files were analyzed to evaluate the mechanical uncertainty in beam localization over the long term (approximately 1 year), as were patterns of patient movements during brain tumor treatments using CyberKnife. METHODS AND MATERIALS: The clinical to planning target volume (CTV-PTV) margin in clinical use was examined based on this analysis. Log-file analysis was performed using data from 140 brain tumor patients (267 treatment plans; 27,166 beams; approximately 66 beams/fraction), who underwent CyberKnife stereotactic radiosurgery and radiation therapy. We calculated a mean error and 2 standard deviations (2σ) for this population. Additionally, we calculated the radius R95% spatially covering 95% of all error vectors. RESULTS: The mean mechanical uncertainties of CyberKnife brain tumor treatment were found to be 0.07, 0.01, and -0.09 mm in the +inferior/-superior, +left/-right, and +anterior/-posterior directions, respectively. The mean (2σ) of R95% was 1.02 (0.42) mm. A smaller degree of correlation between patient movement and R95% was observed. CONCLUSION: The CyberKnife is robust in tracking accuracy, regardless of patient movement. The effectiveness of log-file analysis was demonstrated regarding quality control for monitoring beam localization in the CyberKnife system. The CTV-PTV margin of 2.0 mm was found to be adequate in brain tumor treatments using the CyberKnife.

Dose error from deviation of dwell time and source position for high dose-rate 192Ir in remote afterloading system.

The influence of deviations in dwell times and source positions for (192)Ir HDR-RALS was investigated. The potential dose errors for various kinds of brachytherapy procedures were evaluated. The deviations of dwell time ΔT of a (192)Ir HDR source for the various dwell times were measured with a well-type ionization chamber. The deviations of source position ΔP were measured with two methods. One is to measure actual source position using a check ruler device. The other is to analyze peak distances from radiographic film irradiated with 20 mm gap between the dwell positions. The composite dose errors were calculated using Gaussian distribution with ΔT and ΔP as 1σ of the measurements. Dose errors depend on dwell time and distance from the point of interest to the dwell position. To evaluate the dose error in clinical practice, dwell times and point of interest distances were obtained from actual treatment plans involving cylinder, tandem-ovoid, tandem-ovoid with interstitial needles, multiple interstitial needles, and surface-mold applicators. The ΔT and ΔP were 32 ms (maximum for various dwell times) and 0.12 mm (ruler), 0.11 mm (radiographic film). The multiple interstitial needles represent the highest dose error of 2%, while the others represent less than approximately 1%. Potential dose error due to dwell time and source position deviation can depend on kinds of brachytherapy techniques. In all cases, the multiple interstitial needles is most susceptible.

Studies of the toxicological potential of capsinoids: X. Safety assessment and pharmacokinetics of capsinoids in healthy male volunteers after a single oral ingestion of CH-19 Sweet extract.

The safety and pharmacokinetics of capsinoids, physiologically active ingredients of CH-19 Sweet extract, were investigated in 16 healthy male volunteers following a single oral ingestion of CH-19 Sweet extract. The study subjects consumed soft gel capsules containing either capsinoids (15 or 30 mg/person) or placebo. Capsinoids were well tolerated, and no clinically significant changes in physical examinations, blood pressure, heart rate, body temperature, electrocardiogram, hematology, blood chemistry, and urinalysis were observed at either the 15 or 30 mg dose. Body temperature tended to increase after the ingestion of capsinoids, but remained within the normal range. Plasma levels of capsinoids and their metabolite, vanillyl alcohol, were below the lower limit of quantitation. In addition, some study subjects showed increases in urinary excretion of 3-methoxy-4-hydroxyphenylglycol that, when compared to the group receiving the placebo, did not achieve statistical significance.

Radiophotoluminescence dosimetry using a small spherical glass: a preliminary phantom study.

A radiophotoluminescence dosimetry has been proposed using a spherical silver-activated phosphate glass with a diameter of 1.5 mm. A 6 MV photon dose of 2 Sv (2 Gy) was delivered to 14 spherical glass samples placed between two solid water phantoms at a depth of 10 cm. The samples were positioned within a 20 x 20 mm(2) centred at beam axis to ensure uniform dose absorption. A normalised output from a read-out system was obtained by simultaneously measuring luminescence from a non-irradiated reference and that from an irradiated reference to eliminate background contamination and time-varying fluctuation of the readout system, leading to a normalised standard deviation of 1.8%. A dose up to 3.5 Sv (3.5 Gy) was delivered to three spherical glass samples positioned between two solid water phantoms at a depth of 10 cm. The normalised output increased linearly with the applied dose.

A novel mechanism for drug-induced liver failure: inhibition of histone acetylation by hydralazine derivatives.

BACKGROUND/AIMS: The aim of this study was to investigate the precise mechanism of liver failure by hydralazine derivatives, with special reference to liver regeneration failure. METHODS: Histone acetylation and proliferation of hepatocytes were evaluated by immunohistochemistry with anti-acetylated histone H4 and proliferating cell nuclear antigen (PCNA). Inhibition of histone acetylation by drugs was determined by in vitro histone acetylation assay. Mice livers fed with todralazine for 1 or 4 months were subjected to immunohistochemistry and Western blotting. Todralazine-fed mice were challenged with anti-Fas to check liver regeneration failure. RESULTS: On immunohistochemistry, histone acetylation in the hepatocytes was significantly impaired in patients with hydralazine derivatives. In an in vitro acetyl transferase assay, histone acetylation was inhibited by hydralazine derivatives in a dose-dependent manner. Mice fed with todralazine (3mg/day) for 4 months showed impairment of histone acetylation in hepatocytes whereas no inhibition was observed in mice fed with todralazine for 1 month. Anti-Fas challenge to todralazine-fed mice resulted in impairment of liver regeneration in respect of liver weight loss with impairment of histone acetylation in hepatocytes. CONCLUSIONS: Todralazine could inhibit catalysis of histone acetyltransferase and long-term administration of todralazine may impair histone acetylation of the hepatocytes, resulting in liver regeneration failure.

Development of an easy-to-handle range measurement tool using a plastic scintillator for proton beam therapy.

Proton beam therapy can concentrate the dose on a tumour. In order to offer high-precision proton beam therapy to the patient, it is important to confirm the range every day. At the National Cancer Center Hospital East (NCC), the range measurement tool consists of a water phantom and an ionization chamber. These large and heavy tools take a long time to set up. Therefore, we developed a simple and easy-to-handle range measurement tool for proton beam therapy. This tool consists of a plastic scintillator block and a CCD camera. We recorded visible scintillation light generated by proton irradiation on the scintillator, and could measure the range from the shape of light distribution by using a computer with automatic analysis software installed. We carried out proton irradiation experiments with this tool to examine its performance as a tool of daily range measurements. The precision of the range measurement is within 0.3 mm (sd). The tool can measure possible short-term range variation with 1 s sampling time during the time interval of a typical treatment in a few minutes. We conclude that this tool can measure the range with sufficient resolution in a short time, and is useful for range control in a clinical setting.

[Performance evaluation of X-ray CT using visible scintillation light].

We proposed a new method of performance evaluation for X-ray CT using visible scintillation light and examined its usefulness in this study. When we scanned a plastic scintillator disk in a gantry opening of the X-ray CT, we could observe visible scintillation light. The rotation of the light-emitting area of the disk corresponded to that of the X-ray tube. We were able to record the scintillation light by digital video camera. By analyzing the area of visible scintillation light, the rotation speed of the X-ray tube, angular spread of the X-ray beam, uniformity of the incident X-rays, and change in X-ray energy were measured. No other method is available to obtain the above parameters of X-ray CT during a single CT scan. In the measurements of the uniformity of incident X-rays and change of X-ray energy, our method showed good accuracy in detecting the attenuation caused by the couch between the X-ray tube and the plastic scintillator disc. The proposed method is inexpensive and easy-to-use. We conclude that the method is a useful tool for performance evaluation as well as a maintenance tool for X-ray CT.

Micrometastasis and expression of nm23 messenger RNA of lymph nodes from lung cancer and the postoperative clinical outcome.

BACKGROUND: Based on the metastatic route in lymph nodes from lung cancer, we investigated micrometastasis in the dissected lymph nodes by genetic analysis of keratin 19 and nm23-H1 (the expression of a tumor-metastatic suppressor gene) and evaluated the postoperative outcomes. METHODS: Ten patients operated with lung cancer were 4 males and 6 females, who were stage IA; 2, stage IB; 3, stage IIA; 2, stage IIB; 1, and stage IIIA; 2, respectively. After total RNA extraction from the dissected lymph nodes, the expression of nm23-H1 and keratin 19 messenger ribonucleic acid (mRNA) were analyzed with reverse-transcripted polymerase chain reaction (RT-PCR). RESULTS: The confirmation of micrometastasis in lymph nodes was realized in seven of 10 cases (70%), in their 5-year follow-up term. In three patients there was recurrence (43%, 3/7), and the one of them had died from the mediastinal recurrence. On the expression of nm23-H1 mRNA in lymph nodes, there was no significant difference between the pathologically lymph-node metastasis positive group and the negative one, and between the group with a tumor size over 30 mm and the group with a tumor size under 30 mm, respectively. The expression ratio of nm23-H1 gene was significantly expressed in the group with micrometastasis in lymph nodes (47%, 9/19) as compared to those without micrometastasis (10%, 1/10) (p<0.05). On the all-positive expression of nm23-H1 in the examined lymph nodes (n=4), no patient had recurrence (0%, 0/4). However, in the rest of the six patients without the all-positive expression of nm23-H1 in those lymph nodes (n=6), four patients had recurrence (67%, 4/6). There was no significance between the recurrent ratio in the all-positive expression of nm23-H1 suggesting lower incidence as compared to that in patients without all-positive expression of nm23-H1. CONCLUSION: A detection of micrometastasis in lymph nodes could be a useful tool to identify the subpopulation of patients who might have a higher risk of recurrence and distant metastases. The nm23-H1 gene might be involved in a suppression role for micrometastasis in lymph nodes through the lymphatic route in lung cancer.

Detection of precore-mutant hepatitis B virus genome in patients with acute and fulminant hepatitis using mutation site-specific assay (MSSA).

BACKGROUND/AIMS: Precore mutation of hepatitis B virus was recently been suggested to be involved in the pathogenesis of fulminant hepatitis. In this study, we analyzed the occurrence of precore mutants in patients with acute and fulminant hepatitis B using new simple rapid and sensitive MSSA (mutation site-specific assay) and evaluated this method for predicting prognosis. METHODOLOGY: We analyzed HBV-DNA of 10 patients with fulminant hepatitis B, 15 patients with acute self-limited hepatitis, and 4 patients with acute severe hepatitis using MSSA. Precore point mutation (G to A; 83rd base of precore region) was examined using a mutation-trapped oligonucleotide primer, which would yield a polymerase chain reaction amplification product only with precore mutants. RESULTS: We distinguished precore mutants from wild type according to the presence or absence of the band at 203 bp, which was amplified in only precore mutants by polymerase chain reaction. Mutation of the precore region was observed in all 10 patients with fulminant hepatitis, in 3 of the 4 patients with severe hepatitis, and 11 of 15 patients with self-limited hepatitis. Negative pre-C mutants in patients with HBeAg indicates good prognosis of hepatitis. CONCLUSIONS: Precore mutant strains of HBV-DNA play an important role but are not specific for fulminant hepatitis, and the mere presence of precore mutants may not directly lead to fulminant hepatitis or severe hepatitis. However, this method is useful for predicting outcome of patients with acute HBV hepatitis, especially in HBeAg-positive state.

Pneumothorax after diagnostic laparoscopy.

Here we want to call laparoscopist's attention to pneumothorax after diagnostic laparoscopy. Diagnostic laparoscopy has less complications, compared with laparoscopic surgery. In our experience, only one case (0.04%) developed pneumothorax during routine diagnostic laparoscopic procedure. This complication is presented in a 50-year-old female. She complained of dyspnea just after the decrease of intraabdominal pressure and deflation of intraperitoneal gas. The chest roentgenogram showed a right pneumothorax, and a right chest tube was inserted with immediate relief of tension. Pneumothorax during diagnostic laparoscopy is relatively rare but a major complication; Medline literature research showed six reported cases of pneumothorax after diagnostic laparoscopy from 1983 to 1998 including our case. The etiology was idiopathy in 5 and diaphragmatic injury in 1. Hypotension, elevation of inspiratory pressure, dyspnea, a decrease in systemic oxygen saturation, and loss of breath sounds suggest tension pneumothorax. The clinical condition of the patients improved rapidly because of the easy diffusion of the gas used in laparoscopy. Diagnostic laparoscopists should be aware of this complication and treat ventilatory problems.