PubTransformer

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Gen Suzuki - Top 30 Publications

Long-term Outcomes of a Dose-reduction Trial to Decrease Late Gastrointestinal Toxicity in Patients with Prostate Cancer Receiving Soft Tissue-matched Image-guided Intensity-modulated Radiotherapy.

We experienced an unexpected high incidence of gastrointestinal (GI) toxicity in patients undergoing image-guided intensity-modulated radiotherapy (IG-IMRT) using helical tomotherapy in our initial 2.2 Gy/fraction schedule for prostate cancer; hence, a dose-reduction trial from 2.2 Gy to 2 Gy/fraction was conducted using modified planning target volume (PTV) contouring.

Palliative Reirradiation for Painful Bone Metastases: Clinical Cases and Literature Review.

Reirradiation to previously irradiated peripheral bone metastases for pain has been shown to be safe and effective, but no specific trial has been completed to define the indications for reirradiation of patients with recurrent symptoms of metastatic bone disease. Thus, we aimed to assess the effectiveness and prognostic factors of reirradiation for painful bone metastases. To do so, we reviewed the cases of 14 patients with painful bone metastases who had undergone reirradiation at our hospital. A favorable pain response after reirradiation wasachieved in 50% (7/14) of the patients. An interval from initial radiotherapy >6 months was a significant prognostic factor for pain response (p = 0.03). Performance status was correlated with pain response, with borderline significance (p = 0.06). No severe adverse events were reported. We conclude that reirradiation of painful bone metastases is effective in providing pain relief, especially for patients with a long interval from initial radiation and good performance status.

Radiotherapy for locally advanced resectable T3-T4 laryngeal cancer-does laryngeal preservation strategy compromise survival?

With the advancement of chemotherapy, a laryngeal preservation (LP) strategy was explored with the aim of improving maintenance of quality of life. Induction chemotherapy (ICT) following radiotherapy (RT) was considered a viable option because of its high initial response rate without hampering of overall survival (OS). Subsequently, concurrent chemoradiotherapy (CCRT) using CDDP became the standard of care for LP, showing the best LP ratio. For enhancing treatment intensity, ICT with taxan + CDDP + 5-FU (TPF-ICT) followed by RT showed superiority over ICT with CDDP + 5-FU (PF-ICT) followed by RT. Given that almost all randomized controlled trials investigating ICT include not only operable (endpoint, LP) but also inoperable (endpoint, OS) cases, physicians are faced with a dilemma regarding application in daily practice. In addition, increased treatment intensity causes augmentation of adverse events, which might reduce compliance. Thereafter, cetuximab, an effective drug with fewer adverse effects [bioradiotherapy (BRT)], emerged as another option. However, little evidence has confirmed its superiority over RT (or CCRT) in laryngeal cancer subpopulations. In spite of these developments, the OS of patients with laryngeal cancer has not improved for several decades. In fact, several studies indicated a decrease in OS during the 1990s, probably due to overuse of CCRT. Fortunately, the latter was not the case in most institutions. Currently, no other treatment has better OS than surgery. The eligibility criteria for LP and/or surgery largely depend upon the available expertise and experience, which differ from one institution to another. Therefore, a multidisciplinary team is required for the treatment of LP.

Clinical Usefulness of the Platelet-to Lymphocyte Ratio in Patients with Angiosarcoma of the Face and Scalp.

Angiosarcoma of the face and scalp (ASFS) is an extremely aggressive tumor that frequently metastasizes, often leading to death. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are inflammatory markers that predict outcome of various cancers. We aimed to examine the relationship between pretreatment inflammatory markers and ASFS outcome. We included 17 patients with ASFS and a control group of 56 age- and gender-matched healthy individuals. Total white blood counts, neutrophil, lymphocyte, monocyte, and platelet counts were recorded; NLR, PLR, and LMR were calculated. Kaplan-Meier curves were used to calculate overall survival (OS) and distant metastasis-free survival (DMFS). Optimal cut-off values for each inflammatory marker were calculated using receiver operating curve analysis. Median follow-up was 22 months (range, 6-75). There was a statistically significant difference in absolute neutrophil counts and NLR between patient and control groups. Two-year OS and DMFS rates were 41% and 35%, respectively. In patients with tumors < 10 cm, PLR was highly correlated with DMFS, with the 2-year DMFS for those with a high PLR being 50% compared with 100% for those with a low PLR (p = 0.06). This study suggests that PLR is superior to NLR and LMR, and is a clinically useful marker in patients with ASFS with small tumors.

Interfractional Rectal Displacement Requiring Repeated Precaution Did Not Correlate to Biochemical Control and Rectal Toxicity in Patients with Prostate Cancer Treated with Image-guided Intensity-modulated Radiation Therapy.

To investigate the correlation between frequency of action level of interfractional rectal displacement requiring repeated precaution in patients with prostate cancer and late toxicity from image-guided intensity-modulated radiation therapy (IG-IMRT) using helical tomotherapy.

Brief Myocardial Ischemia Produces Cardiac Troponin I Release and Focal Myocyte Apoptosis in the Absence of Pathological Infarction in Swine.

In a porcine model of brief ischemia leading to reversible stunning in the absence of tissue necrosis, we demonstrated delayed release of cTnI that exceeded the 99th percentile for normals 60-minutes after reperfusion and rose to readily detectable levels 24-hours later. While tissue analysis at 60-minutes showed no evidence of infarction, TUNEL staining demonstrated isolated myocytes undergoing apoptosis, which was absent after 24-hours. These results demonstrate that cTnI elevations occur after ischemia of a duration that is insufficient to produce myocyte necrosis and reflect myocyte injury associated with delayed apoptosis in the absence of pathological evidence of infarction.

Measurement of exhaled nitric oxide and serum surfactant protein D levels for monitoring radiation pneumonitis following thoracic radiotherapy.

The present study aimed to examine the role of exhaled nitric oxide (eNO) and serum surfactant protein D (SP-D) level in the determination of radiation pneumonitis (RP) after thoracic radiotherapy (RT). The study included 34 treatments for 33 patients, including 16 three-dimensional conformal and 18 stereotactic body RT treatments. eNO levels were measured prior to RT, immediately subsequent to RT, every week during the RT course and at 1, 3, 6, 9 and 12 months following the treatment. The therapy reduced the eNO from 24.3±12.8 ppb prior to RT to 19.0±10.4 ppb immediately subsequent to RT (P=0.04). A total of 5 patients (14%) developed symptomatic RP of grade 2 or higher 3-5 months later, and exhibited an eNO elevation of 2.1±0.68-fold the minimum value, whereas the RP- group exhibited 1.4±0.6-fold elevation (P=0.02). The sensitivity of a cut-off of a 1.4-fold increase in the eNO ratio at the onset of RP was 100%; however, the specificity was 52%, and no predictive alterations to eNO levels were observed prior to the onset of RP. RT was associated with an elevated serum SP-D level at 3-6 months after RT. There was a statistically significant difference in the initial serum SP-D level between RP+ and RP- patients. In conclusion, obtaining the eNO ratio was a useful RP monitoring tool but did not predict RP occurrence in the present setting, whereas serum SP-D level may be a potential predictor for the detection of RP risk.

Local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer.

Radiotherapy is an effective treatment for the postoperative loco-regional recurrence of esophageal cancer; however, the optimal treatment field remains controversial. This study aims to evaluate the outcome of local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer.

Radiotherapy for laryngeal cancer-technical aspects and alternate fractionation.

Early laryngeal, especially glottic, cancer is a good candidate for radiotherapy because obvious early symptoms (e.g. hoarseness) make earlier treatment possible and with highly successful localized control. This type of cancer is also a good model for exploring the basic principles of radiation oncology and several key findings (e.g. dose, fractionation, field size, patient fixation, and overall treatment time) have been noted. For example, unintended poor outcomes have been reported during transition from 60Cobalt to linear accelerator installation in the 1960s, with usage of higher energy photons causing poor dose distribution. In addition, shell fixation made precise dose delivery possible, but simultaneously elevated toxicity if a larger treatment field was necessary. Of particular interest to the radiation therapy community was altered fractionation gain as a way to improve local tumor control and survival rate. Unfortunately, this interest ceased with advancements in chemotherapeutic agents because alternate fractionation could not improve outcomes in chemoradiotherapy settings. At present, no form of acceleration can potentially compensate fully for the lack of concurrent chemotherapy. In addition, the substantial workload associated with this technique made it difficult to add extra fractionation routinely in busy clinical hospitals. Hypofractionation, on the other hand, uses a larger single fractionation dose (2-3 Gy), making it a reasonable and attractive option for T1-T2 early glottic cancer because it can improve local control without the additional workload. Recently, Japan Clinical Oncology Group study 0701 reprised its role in early T1-T2 glottic cancer research, demonstrating that this strategy could be an optional standard therapy. Herein, we review radiotherapy history from 60Cobalt to modern linear accelerator, with special focus on the role of alternate fractionation.

Effect of intratumoral abscess/necrosis on the outcome for head and neck cancer patients treated by hypofractionated stereotactic re-irradiation using CyberKnife®.

The aim of the present study was to elucidate the effect of intratumoral abscess/necrosis (AN) on the outcome of patients with recurrent head and neck cancer (HNC) treated by stereotactic radiotherapy. The records of 67 patients treated with CyberKnife® in four institutes between August 2000 and July 2010 were reviewed. The frequency of AN appeared to be increased in younger postoperative patients with large ulcerative tumors. The AN+ group exhibited a better initial response rate compared with the AN- group (64 vs. 33%, respectively; P=0.04). The 1-year local control rate was 51 and 75% in the AN+ and AN- groups, respectively (P=0.01), while the respective 1-year overall survival rates were 53 and and 71% (P=0.0004). A total of 21 patients (31%) experienced grade ≥3 toxicities, and carotid blowout syndrome (CBOS) was found in 11 patients, resulting in 8 deaths. A significantly larger proportion of patients in the AN+ group developed CBOS (8/18; 44%) compared with the AN- group (3/49; 6%) (P=0.001). Therefore, AN may be an important prognostic factor for patients with recurrent HNC, as well as a predictor of lethal toxicity due to CBOS.

Body Surface Contamination Levels of Residents under Different Evacuation Scenarios after the Fukushima Daiichi Nuclear Power Plant Accident.

Body surface contamination levels should be correlated with inhaled actual thyroid doses during evacuation following the Fukushima Daiichi nuclear power plant (FDNPP) accident. Evacuees and residents were screened for body surface contamination using a Geiger-Mueller survey meter. The authors obtained 7,539 individual screening data sheets as well as gamma-spectrometry data from measurements made on clothing of two subjects by using a germanium spectrometer. Body surface contamination levels were analyzed in four residential groups during two different periods: 12-14 and 15-17 March 2011. Contamination levels during 12-14 March in the Tomioka/Okuma/Futaba/Naraha group were very low, indicating that residents evacuated before the radioactive plume reached their towns on 12 March. In contrast, levels in the Namie and Minamisoma groups were higher than those in the other groups in both periods, indicating that these residents were exposed to plumes twice on 12 and 15-16 March. The plume on 12 March was enriched with short-lived radionuclides: averaged proportions of radioactivity (relative to I) from Te, I, and Cs measured in clothing from two subjects were 2.3, 1.1, and 0.1, respectively, after correction for physical decay by 12:00 on 12 March. These proportions are similar to those (relative to I) from Te and Cs in dust sampled by a high-volume air sampler in the zone 20 km from the FDNPP on 12 March: 1.9 and 0.1, respectively. These data indicate that the relative contribution to inhaled thyroid dose of short-lived radionuclides in radioactive plumes released on 12 March could be as much as 37.5% in 1-y-old children.

Clinical outcome of patients treated with re-irradiation for spine or pelvic bone metastasis: A multi-institutional analysis of 98 patients.

The present study aimed to describe the clinical results of re-irradiation (Re-RT) for spine or pelvic bone metastasis at the same initial irradiated area. Between April 2010 and March 2014, cases involving 98 patients with spine or pelvic bone metastasis who had undergone Re-RT at five institutions were reviewed. The clinical outcomes following Re-RT were evaluated, including overall survival (OS) and severe adverse events. The median time interval from initial radiation therapy (RT) to Re-RT was 439 days (range, 23-4,993 days), and the median duration of patient follow-up was 256 days (range, 11-2,284 days). The median biological effective dose for the Re-RT was 150 Gy2 (range, 17-240 Gy2; α/β = 2). Severe late adverse events occurred in two patients who underwent three-dimensional conformal radiotherapy for lumbar spine or pelvic bone metastases, which may be associated with tumor progression. The median survival time following Re-RT was 255 days, and the actuarial OS rate at 1 year was 36%. The interval between initial RT and Re-RT, and their performance statuses (PS) were significant independent prognostic factors for OS rates in multivariate analysis. Re-RT for spine or pelvic bone metastases is a relatively acceptable option with low risk of anticipated severe adverse events, particularly for patients with good PS following a long disease-free interval.

Palliative Radiotherapy in the Local Management of Stage IVB Esophageal Cancer: Factors Affecting Swallowing and Survival.

To clarify the role of external-beam radiotherapy in the local management of state IVB esophageal cancer.

Reply: Weil's Response.

Reirradiation for recurrent head and neck cancers using charged particle or photon radiotherapy.

To examine the outcomes of reirradiation for recurrent head and neck cancers using different modalities.

Surveys of Food Intake Just after the Nuclear Accident at the Fukushima Daiichi Nuclear Power Station.

As a result of the nuclear accident at the Fukushima Daiichi nuclear power station (FDNPS) after the Great East Japan Earthquake on March 11, 2011, volatile radionuclides including iodine-131 were released into the environment and contaminated open-field vegetables, raw milk, tap water, etc. It is important for the health care of residents to correctly comprehend the level of their exposure to radioactive substances released following the accident. However, an evaluation of the internal exposure doses of residents of Fukushima Prefecture as a result of the ingestion of foods, which is indicated in the report issued by United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR)1 is based on a number of assumptions. For instance, the estimation assumes that foods were ingested as usual, without regard to the places to which residents were evacuated after the accident, the places where food shipment restrictions were imposed, and so forth. The present report aims to improve the accuracy of estimation of the amount of food actually ingested at evacuation areas, in order to reduce as much as possible the level of uncertainty in conventional values estimated directly after the accident, which were in fact values based on conservative assumptions. More concretely, as basic source material to more accurately estimate internal exposure doses from food ingestion, various patterns of evacuation and dietary habits at the time of the accident of the residents of 13 municipalities in Fukushima Prefecture who were evacuated during the period from directly after the accident of March 11, 2011 until the end of March are clarified in this report. From survey results, most of the food that evacuees took immediately after the accident was confirmed to have been sourced from either stockpiles prepared before the accident, or relief supplies from outside of the affected areas. The restriction orders of food supplies such as contaminated vegetables and milk, and tap water intake were implemented within several days after the major release of radionuclides on March 15, 2011. In addition, collapse in supply chains, i.e., damage to distribution facilities, lack of transportation vehicles or electricity, and the closure of retail stores, contributed to a situation where food or supplies contaminated with iodine -131 were not consumed in large quantities in general, even before the food restriction order. Since people consumed tap water and water from other sources before the implementation of restriction orders in affected areas, we surveyed the status of water as a potential route of internal exposure.

In Regard to Phan et al.

Comment on "Effect of tumor dose, volume and overall treatment time on local control after radiochemotherapy including MRI guided brachytherapy of locally advanced cervical cancer" Kari Tanderup et al.

Myocardial and Serum Galectin-3 Expression Dynamics Marks Post-Myocardial Infarction Cardiac Remodelling.

Acute myocardial infarction (MI) causes significant changes in cardiac morphology and function. Galectin-3 is a novel and potentially therapeutically important mediator of cardiac remodelling. Myocardial and serum galectin-3 expression dynamics in response to the early cardiovascular outcomes after acute MI are not fully elucidated.

Comparative Hemodynamic Effects of Contemporary Percutaneous Mechanical Circulatory Support Devices in a Porcine Model of Acute Myocardial Infarction.

The aim of this study was to directly compare the hemodynamic effects of 2 contemporary percutaneous mechanical circulatory support devices in a porcine model of acute myocardial infarction.

Definitive Radiation Therapy for Angiosarcoma of the Face and Scalp.

To examine the role of radiation therapy (RT) and factors' influence on tumor control for angiosarcoma of the face and scalp (AS-FS).

Comparison of Re-irradiation Outcomes for Charged Particle Radiotherapy and Robotic Stereotactic Radiotherapy Using CyberKnife for Recurrent Head and Neck Cancers: A Multi-institutional Matched-cohort Analysis.

To compare survival outcomes for charged particle radiotherapy (CP) and stereotactic body radiotherapy using CyberKnife (CK) in patients who had undergone re-irradiation for head and neck cancers.

Heart-Derived Stem Cells in Miniature Swine with Coronary Microembolization: Novel Ischemic Cardiomyopathy Model to Assess the Efficacy of Cell-Based Therapy.

A major problem in translating stem cell therapeutics is the difficulty of producing stable, long-term severe left ventricular (LV) dysfunction in a large animal model. For that purpose, extensive infarction was created in sinclair miniswine by injecting microspheres (1.5 × 106 microspheres, 45 μm diameter) in LAD. At 2 months after embolization, animals (n = 11) were randomized to receive allogeneic cardiosphere-derived cells derived from atrium (CDCs: 20 × 106, n = 5) or saline (untreated, n = 6). Four weeks after therapy myocardial function, myocyte proliferation (Ki67), mitosis (phosphor-Histone H3; pHH3), apoptosis, infarct size (TTC), myocyte nuclear density, and cell size were evaluated. CDCs injected into infarcted and remodeled remote myocardium (global infusion) increased regional function and global function contrasting no change in untreated animals. CDCs reduced infarct volume and stimulated Ki67 and pHH3 positive myocytes in infarct and remote regions. As a result, myocyte number (nuclear density) increased and myocyte cell diameter decreased in both infarct and remote regions. Coronary microembolization produces stable long-term ischemic cardiomyopathy. Global infusion of CDCs stimulates myocyte regeneration and improves left ventricular ejection fraction. Thus, global infusion of CDCs could become a new therapy to reverse LV dysfunction in patients with asymptomatic heart failure.

Rationale and design of Diabetes Prevention with active Vitamin D (DPVD): a randomised, double-blind, placebo-controlled study.

Recent research suggests that vitamin D deficiency may cause both bone diseases and a range of non-skeletal diseases. However, most of these data come from observational studies, and clinical trial data on the effects of vitamin D supplementation on individuals with pre-diabetes are scarce and inconsistent. The aim of the Diabetes Prevention with active Vitamin D (DPVD) study is to assess the effect of eldecalcitol, active vitamin D analogue, on the incidence of type 2 diabetes among individuals with pre-diabetes.

Widespread Intracoronary Cardiopoietic Cell Infusion: Treating at the Time of Myocardial Reperfusion to Prevent Rather Than Reverse Established Left Ventricular Dysfunction Moves Us Closer to Practical Clinical Translation.

Reirradiation using robotic image-guided stereotactic radiotherapy of recurrent head and neck cancer.

The purpose of this study was to examine the prognosis for patients with head and neck cancer after reirradiation using Cyberknife stereotactic body irradiation with special focus on mucosal ulceration. We conducted a retrospective multi-institutional review of 107 patients with previously irradiated head and neck cancer. The median follow-up time for all patients was 15 months, and the 2-year overall survival rate was 35%. Significant prognostic factors for overall survival were primary site (nasopharynx versus other sites), presence of ulceration, and PTV volume. Detailed analysis of ulceration showed a lower response rate (28%) in the ulceration (+) group than the ulceration (-) group (63%; P = 0.0045). The 2-year overall survival rates were 8% in the ulceration (+) group and 42.7% (P = 0.0001) in the ulceration (-) group, respectively. We recorded 22 severe toxicities, including 11 patients with carotid blow-out syndrome (CBOS), which was fatal in 9 patients. CBOS occurred in 6 patients with ulceration (6/25; 24%), and 5 patients experienced CBOS without ulceration (5/82; 6%; P=0.027). In conclusion, ulceration is an important prognostic factor, not only for adverse events but also for survival after reirradiation using CyberKnife.

Development of an Improved Inhalable Powder Formulation of Pirfenidone by Spray-Drying: In Vitro Characterization and Pharmacokinetic Profiling.

Previously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk; however, PFD-RP demonstrated unacceptable in vitro inhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method.

Comparative study on prediction performance of photosafety testing tools on photoallergens.

Several testing methods have been established to identify potential phototoxins. The present study was undertaken to clarify the predictive ability of in vitro photosafety assays for photoallergenicity. On the basis of animal and/or clinical photosafety information, 23 photoallergens and 7 non-phototoxic/non-photoallergenic chemicals were selected and subjected to UV/VIS spectral analysis, reactive oxygen species (ROS)/micellar ROS (mROS) assays, and 3T3 neutral red uptake phototoxicity testing (3T3 NRU PT). Of the photoallergens tested, ca. 96% of chemicals had intense UV/VIS absorption with a molar extinction coefficient of over 1000 M(-1) cm(-1), and false-positive predictions were made for 3 non-photoallergenic chemicals. In the ROS assay, all photoallergens were found to be potent ROS generators under exposure to simulated sunlight. In the photosafety prediction based on the ROS assay, the individual specificity was 85.7%, and the positive predictivity and negative predictivity were found to be 95.8% and 100%, respectively. Most of the photoirritant chemicals were correctly identified by the 3T3 NRU PT; however, it provided false predictions for ca. 48% of photoallergens. The orders of sensitivity and specificity for photoallergenicity prediction were estimated to be: [sensitivity] ROS assay>UV/VIS absorption ≫ 3T3 NRU PT, and [specificity] 3T3 NRU PT>ROS assay ≫ UV/VIS absorption. Thus, photochemical assays, in particular the ROS assay, can be used for assessment of photoallergenicity, although there were some false-positive predictions.

Translational research of adult stem cell therapy.

Congestive heart failure (CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.

Superiority of charged particle therapy in treatment of hepatocellular carcinoma (Regarding Qi W.X. et al. charged particle therapy versus photon therapy for patients with hepatocellular carcinoma: A systematic review and meta-analysis).