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1.
Chem Sci ; 15(11): 4019-4030, 2024 Mar 13.
Article En | MEDLINE | ID: mdl-38487248

The development of boron delivery agents bearing an imaging capability is crucial for boron neutron capture therapy (BNCT), yet it has been rarely explored. Here we present a new type of boron delivery agent that integrates aggregation-induced emission (AIE)-active imaging and a carborane cluster for the first time. In doing so, the new boron delivery agents have been rationally designed by incorporating a high boron content unit of a carborane cluster, an erlotinib targeting unit towards lung cancer cells, and a donor-acceptor type AIE unit bearing naphthalimide. The new boron delivery agents demonstrate both excellent AIE properties for imaging purposes and highly selective accumulation in tumors. For example, at a boron delivery agent dose of 15 mg kg-1, the boron amount reaches over 20 µg g-1, and both tumor/blood (T/B) and tumor/normal cell (T/N) ratios reach 20-30 times higher than those required by BNCT. The neutron irradiation experiments demonstrate highly efficient tumor growth suppression without any observable physical tissue damage and abnormal behavior in vivo. This study not only expands the application scopes of both AIE-active molecules and boron clusters, but also provides a new molecular engineering strategy for a deep-penetrating cancer therapeutic protocol based on BNCT.

2.
Sci Rep ; 14(1): 418, 2024 01 03.
Article En | MEDLINE | ID: mdl-38172585

Boron Neutron Capture Therapy (BNCT) is a radiotherapy technique based on the enrichment of tumour cells with suitable 10-boron concentration and on subsequent neutron irradiation. Low-energy neutron irradiation produces a localized deposition of radiation dose caused by boron neutron capture reactions. Boron is vehiculated into tumour cells via proper borated formulations, able to accumulate in the malignancy more than in normal tissues. The neutron capture releases two high-LET charged particles (i.e., an alpha particle and a lithium ion), losing their energy in a distance comparable to the average dimension of one cell. Thus BNCT is selective at the cell level and characterized by high biological effectiveness. As the radiation field is due to the interaction of neutrons with the components of biological tissues and with boron, the dosimetry requires a formalism to express the absorbed dose into photon-equivalent units. This work analyzes a clinical case of an adenoid cystic carcinoma treated with carbon-ion radiotherapy (CIRT), located close to optic nerve and deep-seated as a practical example of how to apply the formalism of BNCT photon isoeffective dose and how to evaluate the BNCT dose distribution against CIRT. The example allows presenting different dosimetrical and radiobiological quantities and drawing conclusions on the potential of BNCT stemming on the clinical result of the CIRT. The patient received CIRT with a dose constraint on the optic nerve, affecting the peripheral part of the Planning Target Volume (PTV). After the treatment, the tumour recurred in this low-dose region. BNCT was simulated for the primary tumour, with the goal to calculate the dose distribution in isoeffective units and a Tumour Control Probability (TCP) to be compared with the one of the original treatment. BNCT was then evaluated for the recurrence in the underdosed region which was not optimally covered by charged particles due to the proximity of the optic nerve. Finally, a combined treatment consisting in BNCT and carbon ion therapy was considered to show the consistency and the potential of the model. For the primary tumour, the photon isoeffective dose distribution due to BNCT was evaluated and the resulted TCP was higher than that obtained for the CIRT. The formalism produced values that are consistent with those of carbon-ion. For the recurrence, BNCT dosimetry produces a similar TCP than that of primary tumour. A combined treatment was finally simulated, showing a TCP comparable to the BNCT-alone with overall dosimetric advantage in the most peripheral parts of the treatment volume. Isoeffective dose formalism is a robust tool to analyze BNCT dosimetry and to compare it with the photon-equivalent dose calculated for carbon-ion treatment. This study introduces for the first time the possibility to combine the dosimetry obtained by two different treatment modalities, showing the potential of exploiting the cellular targeting of BNCT combined with the precision of charged particles in delivering an homogeneous dose distribution in deep-seated tumours.


Boron Neutron Capture Therapy , Head and Neck Neoplasms , Heavy Ion Radiotherapy , Humans , Boron Neutron Capture Therapy/methods , Boron , Carbon , Neutrons
3.
Ying Yong Sheng Tai Xue Bao ; 34(10): 2835-2844, 2023 Oct.
Article Zh | MEDLINE | ID: mdl-37897292

Mineral soil respiration, a major component of CO2 emissions from soil to atmosphere, plays a critical role in driving terrestrial ecosystem carbon cycling and is highly sensitive to environmental changes, including soil temperature, soil moisture, and substrate availability. The changes of environmental factors can affect mineral soil respiration and its temperature sensitivity thereby alters global carbon balance. We reviewed studies on the effects of environmental factors on mineral soil respiration and its temperature sensitivity. The effect of environmental factors on mineral soil respiration and its temperature sensitivity significantly differed among ecosystems. Environmental factors directly and indirectly affect mineral soil respiration and its temperature sensitivity by altering soil microbial biomass and community structure, extracellular enzyme activity, and soil porosity. Based on the results of this review, we suggested: 1) combining multiple observation techniques and methods to study the effects of environmental factors on mineral soil respiration; 2) exploring the interactive effects of multiple environmental factors on mineral soil respiration; 3) carrying out experiments on mineral soil respiration at different temporal and spatial scales; 4) improving the prediction model of mineral soil respiration and its temperature sensitivity; 5) streng-thening the role of substrate supply of recent photosynthates in the regulation of mineral soil respiration and its temperature sensitivity.


Ecosystem , Soil , Soil/chemistry , Biomass , Temperature , Respiration , Carbon , Soil Microbiology , Carbon Dioxide/analysis
4.
Ying Yong Sheng Tai Xue Bao ; 34(6): 1693-1702, 2023 Jun.
Article En | MEDLINE | ID: mdl-37694432

As an important parameter of forests growth, fine root lifespan plays an important role in plant water and nutrient absorption, and affects underground distribution of photosynthetic products and forest ecosystem carbon cycling. The impact of climate warming on fine root lifespan has become a hot issue under the context of global change. The responses of fine root lifespan to global warming will affect ecosystem carbon balance. We reviewed the research progress of the response characteristics and mechanism of fine root lifespan of trees to warming. Most stu-dies proposed that warming would affect fine root lifespan by changing rhizosphere soil environment, fine root morphology, and tree phenology. However, the growth and death of fine roots were affected by lots of factors, leading to differences in the research results on fine root lifespan due to natural environment of the study area, the way of warming, and the research objects. Therefore, it is of importance to comprehensively analyze the responses of fine root lifespan in forests under the background of climate warming to study the underground ecological process. In the future, the following research should be strengthened: 1) Combining multiple methods to warming underground and aboveground simutaneously, and explore more accurate and effective non-destructive observation methods. 2) Combining multiple observations to study the effects of warming on fine root lifespan. 3) Carrying out research on the effect of warming on fine root lifespan of different tree species, and deeply understand the response mechanism of fine root lifespan of different trees to warming. 4) A comprehensive analysis of the effects of warming on fine root lifespan from various perspectives, and an investigation into the mechanism of the combined effects of various factors on fine root lifespan. 5) The interaction between warming and other environmental factors fine root lifespan. 6) The effect of root architecture on the fine root lifespan after warming. 7) The effects of rhizosphere microorganisms (bacteria and fungi) on fine root lifespan after warming.


Ecosystem , Longevity , Forests , Trees , Carbon
5.
Sci Rep ; 13(1): 15701, 2023 09 21.
Article En | MEDLINE | ID: mdl-37735580

NeuMANTA is a new generation boron neutron capture therapy (BNCT)-specific treatment planning system developed by the Neuboron Medical Group and upgraded to an important feature, a Hounsfield unit (HU)-based material conversion algorithm. The range of HU values was refined to 96 specific groups and established corresponding to tissue information. The elemental compositions and mass densities have an important effect on the calculated dose distribution. The region of interest defined in the treatment plan can be converted into multiple material compositions based on HU values or assigned specified single material composition in NeuMANTA. Different material compositions may cause normal tissue maximum dose rates to differ by more than 10% in biologically equivalent doses and to differ by up to 6% in physically absorbed doses. Although the tumor has a lower proportion of BNCT background dose, the material composition difference may affect the minimum dose of biologically equivalent dose and physically absorbed dose by more than 3%. In addition, the difference in material composition could lead to a change in neutron moderation as well as scattering. Therefore, the material composition has a significant impact on the assessment of normal tissue side effects and tumor control probability. It is essential for accurate dose estimation in BNCT.


Boron Neutron Capture Therapy , Drug-Related Side Effects and Adverse Reactions , Humans , Algorithms , Neutrons , Probability
6.
Sci Rep ; 13(1): 15741, 2023 09 21.
Article En | MEDLINE | ID: mdl-37735579

Most treatment planning systems of boron neutron capture therapy perform dose calculations based on the assumption of a homogeneous boron distribution in tumors, which leads to dose distortion due to the difference between the tumor-to-normal tissue ratio (TNR) range measured in positron emission tomography images (PET) and the target delineation in computed tomography images of the treatment plan. The heterogeneous boron distribution in the target of the treatment plan can be obtained by image fusion. This study provides a way to quantify a heterogeneous boron distribution based on PET images. Theoretically, the same mean TNR for dose calculation by homogeneous or heterogeneous boron distribution should get almost the same mean dose. However, slightly different mean doses are found due to the partial volume effect for a small target volume. The wider the boron distribution is, the higher the impact on the dose-volume histogram distribution is. Dose distribution with homogeneous boron distribution may be overestimated in low boron uptake regions by wrong boron concentration and neutron flux depression. To accurately give the tumor prescription dose and achieve better tumor control, for low dose regions of the tumor should be considered more boron neutron capture therapy treatments or combined with other treatment modalities. The heterogeneous boron distribution must be taken into consideration to have an accurate dose estimation. Therefore, the way how medical physicists and clinicians process the TNR in gross tumor volume should be refined, and the method demonstrated in the work provides a good reference.


Boron Neutron Capture Therapy , Neoplasms , Humans , Boron , Neoplasms/diagnostic imaging , Neoplasms/radiotherapy , Biological Transport , Neutrons
7.
Sci Rep ; 13(1): 11965, 2023 Jul 24.
Article En | MEDLINE | ID: mdl-37488142

The Monte Carlo method is the most commonly used dose calculation method in the field of boron neutron capture therapy (BNCT). General-purpose Monte Carlo (MC) code (e.g., MCNP) has been used in most treatment planning systems (TPS) to calculate dose distribution, which takes overmuch time in radiotherapy planning. Based on this, we developed COMPASS (COMpact PArticle Simulation System), an MC engine specifically for BNCT dose calculation. Several optimization algorithms are used in COMPASS to make it faster than general-purpose MC code. The parallel computation of COMPASS is performed by the message passing interface (MPI) library and OpenMP commands, which allows the user to increase computational speed by increasing the computer configurations. The physical dose of each voxel is calculated for developing a treatment plan. Comparison results show that the computed dose distribution of COMPASS is in good agreement with MCNP, and the computational efficiency is better than MCNP. These results validate that COMPASS has better performance than MCNP in BNCT dose calculation.

8.
Nutr Metab Cardiovasc Dis ; 33(5): 1087-1092, 2023 05.
Article En | MEDLINE | ID: mdl-36958971

BACKGROUND AND AIMS: In observational studies, statins have been suggested to have protective effects on venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). To this aim, we performed a two-sample mendelian randomization (MR) analysis to determine whether these associations were causal. METHODS AND RESULTS: Data on the single nucleotide polymorphisms (SNPs) related to statin medication were obtained from the FinnGen study, and data for VTE, PE and DVT of lower extremities (LEDVT) were from the UK Biobank study, respectively. Inverse variance weighted (IVW) method was used as the principal analysis of MR, and sensitivity analysis was performed to detect horizontal pleiotropy and heterogeneity. MR estimates showed an inverse causal association between statin medication and the risk of VTE (odds ratio [OR]: 0.999, 95% CI: 0.998-1.000, P = 0.004), PE (OR: 0.999, 95% CI: 0.999-1.000, P = 0.011) and LEDVT (OR: 0.999, 95% CI: 0.999-1.000, P = 0.008). CONCLUSION: Our findings provide direct evidence that statins might decrease the risk of VTE, PE and LEDVT in agreement with observational studies. The specific mechanism of statin therapy for venous thromboembolism needs to be further studied.


Hydroxymethylglutaryl-CoA Reductase Inhibitors , Pulmonary Embolism , Venous Thromboembolism , Venous Thrombosis , Humans , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology , Venous Thromboembolism/genetics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Mendelian Randomization Analysis , Venous Thrombosis/diagnosis , Venous Thrombosis/epidemiology , Venous Thrombosis/genetics , Pulmonary Embolism/diagnosis , Pulmonary Embolism/epidemiology , Pulmonary Embolism/genetics
9.
Sci Total Environ ; 866: 161362, 2023 Mar 25.
Article En | MEDLINE | ID: mdl-36610618

Biofloc technology, extensively used in intensive aquaculture systems, can prompt the formation of microbial aggregates. Microplastics (MPs) are detected abundantly in aquaculture waters. This study explored the effects of MPs on biofloc formation, microbial community composition and nitrogen transformation function in simulated biofloc aquaculture production systems. The formation process and settling performance of bioflocs were examined. High-throughput sequencing of 16S and 18S rRNA genes was used to investigate the microbial community compositions of bioflocs. Nitrogen dynamics were monitored and further explained from functional genes and microorganisms related to nitrogen transformation by metagenome sequencing. We found that the aggregates consisting of bioflocs and MPs were formed and the systems with MPs had relatively weak settling performance. No significant differences in bacterial diversity (p > 0.05) but significant differences in eukaryotic diversity (p < 0.05) were found between systems without and with MPs. Significant separations in the microbial communities of prokaryotes (p = 0.01) and eukaryotes (p = 0.01) between systems without and with MPs were observed. The peak concentration of nitrite nitrogen (NO2--N) in systems with MPs was lower than that in systems without MPs (pControl/MPs Low = 0.02 and pControl/MPs High = 0.03), probably due to the low abundance of hao and affiliated Alphaproteobacteria_bacterium_HGW-Alphaproteobacteria-1 and Alphaproteobacteria_bacterium, but the high abundance of nxrA and affiliated Alphaproteobacteria_bacterium_SYSU_XM001 and Hydrogenophaga_pseudoflava that related to nitrification. The low concentration of NO2--N in systems with MPs suggested that the presence of MPs might inhibit ammonia oxidation but promote nitrite oxidation by altering the microbial community structure and function. These results indicated that aggregates consisting of bioflocs and MPs could be formed in aquaculture water, and thus, inhibiting their settlement and altering nitrogen transformation function by affecting the microbial community composition.


Microbiota , Microplastics , Plastics , Nitrogen , Nitrogen Dioxide , Aquaculture/methods
10.
Chem Commun (Camb) ; 57(71): 8953-8956, 2021 Sep 06.
Article En | MEDLINE | ID: mdl-34486586

A reliable copper-mediated nucleophilic radiosynthesis of the PET imaging probe [18F]FBPA was developed using novel aryldiboron precursors. The carrier-free [18F]FBPA with radiochemical purity >99% was prepared routinely via the two-step synthesis with an automatic module and can be used for clinical PET imaging of tumours.


Boron Compounds/chemistry , Phenylalanine/analogs & derivatives , Radiopharmaceuticals/chemistry , Animals , Boron Compounds/chemical synthesis , Fluorine Radioisotopes/chemistry , Phenylalanine/chemical synthesis , Positron-Emission Tomography , Radiopharmaceuticals/chemical synthesis
11.
Biology (Basel) ; 10(5)2021 Apr 26.
Article En | MEDLINE | ID: mdl-33925863

Boron Neutron Capture Therapy (BNCT) is a binary radiation treatment exploiting a nuclear reaction occurring in tumor cells [...].

12.
Biology (Basel) ; 10(3)2021 Feb 26.
Article En | MEDLINE | ID: mdl-33652642

(1) Background:The quality of neutron beams for Boron Neutron Capture Therapy (BNCT) is currently defined by its physical characteristics in air. Recommendations exist to define whether a designed beam is useful for clinical treatment. This work presents a new way to evaluate neutron beams based on their clinical performance and on their safety, employing radiobiological quantities. (2) Methods: The case study is a neutron beam for deep-seated tumors from a 5 MeV proton beam coupled to a beryllium target. Physical Figures of Merit were used to design five beams; however, they did not allow a clear ranking of their quality in terms of therapeutic potential. The latter was then evaluated based on in-phantom dose distributions and on the calculation of the Uncomplicated Tumor Control Probability (UTCP). The safety of the beams was also evaluated calculating the in-patient out-of-beam dosimetry. (3) Results: All the beams ensured a UTCP comparable to the one of a clinical beam in phantom; the safety criterion allowed to choose the best candidate. When this was tested in the treatment planning of a real patient treated in Finland, the UTCP was still comparable to the one of the clinical beam. (4) Conclusions: Even when standard physical recommendations are not met, radiobiological and dosimetric criteria demonstrate to be a valid tool to select an effective and safe beam for patient treatment.

13.
Radiat Res ; 195(4): 347-354, 2021 04 01.
Article En | MEDLINE | ID: mdl-33513230

The success of boron neutron capture therapy (BNCT) mainly depends on the boron concentration in the tumor and a high tumor/normal tissue (T/N) boron ratio or a high tumor/blood (T/B) boron ratio. Therefore, the effective enhancement of boron ratios is the first priority. Our study investigated whether a low-dose of γ-radiation (LDR) could improve boron ratios and enhance the therapeutic effects of BNCT in an orthotopic human oral squamous cell carcinoma-bearing animal model. SAS/luc cells were used to establish the orthotopic tumor-bearing model. The pharmacokinetics of boronophenylalanine (BPA) administration with 400 mg/kg of body weight both alone and in combination with LDR (0.1 Gy) was evaluated, and BNCT was performed at the Tsing Hua Open-pool Reactor (THOR). The radiation doses were evaluated using a treatment planning system. Moreover, tumor growth and metastasis were monitored via bioluminescence imaging (BLI). The therapeutic effects after BNCT were evaluated using BLI, histopathological findings and the overall survival rate. LDR increased the BPA accumulation in tumors by 52.2%. T/N and T/B ratios were enhanced from 3.77 to 5.31 and from 3.47 to 4.46, respectively. Radiation dose was increased by 44.3%. Notably, tumor recurrence and cervical lymph node metastasis were observed in the BNCT group, which had a survival rate of 50%. Complete responses were found in the combined-treatment group, which had a survival rate of 100%. No toxicity was found according to the histopathological findings. Conclusively, LDR increased BPA accumulation in the tumor and the T/N and T/B ratios, resulting in BNCT efficacy improvement and the overall survival rate extension.


Boron Compounds/blood , Boron Neutron Capture Therapy , Carcinoma, Squamous Cell/radiotherapy , Mouth Neoplasms/radiotherapy , Animals , Carcinoma, Squamous Cell/blood , Cell Line, Tumor , Disease Models, Animal , Heterografts , Humans , Male , Mouth Neoplasms/pathology , Radiotherapy Dosage , Survival Rate
14.
Appl Radiat Isot ; 167: 109392, 2021 Jan.
Article En | MEDLINE | ID: mdl-33065400

The 7Li(p,n)7Be reaction, which leads to a soft neutron field, is often chosen as the neutron producing reaction used for accelerator-based boron neutron capture therapy (AB-BNCT). This study aims to design a compact beam shaping assembly (BSA) and auxiliary system for a 7Li(p,n)7Be reaction-based neutron source and to evaluate the relationship between the BSA design and the consequent neutron beam quality for further optimization. In this study, five types of moderator shapes for the BSA model were designed. Both the in-air and in-phantom figures of merit were considered to evaluate the performance of the BSA designs. It was found that the BSA with a bi-tapered and air-gapped design could generate a high-intensity epithermal neutron beam, which could be used to treat deep-seated brain tumors within a reasonable time.


Boron Neutron Capture Therapy/instrumentation , Equipment Design , Brain Neoplasms/radiotherapy , Humans , Monte Carlo Method , Neutrons , Phantoms, Imaging
15.
Appl Radiat Isot ; 161: 109143, 2020 Jul.
Article En | MEDLINE | ID: mdl-32250842

The whole picture of the BNCT facility at Tsing Hua Open-pool Reactor will be presented which consists of the following aspects: the construction project, the beam quality, routine operations including the QA program for the beam delivery, determination of boron-10 concentration in blood, T/N ratio, and the clinical affairs including the patient recruit procedure and the patient irradiation procedure. The facility is positioned to serve for conducting clinical trials, emergent (compassionate) treatments, and R&D works.


Boron Neutron Capture Therapy , Neoplasms/radiotherapy , Nuclear Reactors , China , Facility Design and Construction , Humans , Phantoms, Imaging , Radiotherapy Planning, Computer-Assisted/methods , Remission Induction , Survival Rate
16.
Acta Cardiol Sin ; 33(4): 450-452, 2017 Jul.
Article En | MEDLINE | ID: mdl-29033518

BACKGROUND: Cardiac device-related infective endocarditis is an uncommon but potentially fatal complication. Therefore, cardiac devices should be removed as soon as a device-related infection is suspected. CASE REPORT: A 56-year-old male with a history of arrhythmogenic right ventricular dysplasia with implantable cardioverter-defibrillators (ICDs) 7 years earlier and re-implantation of ICDs due to dysfunction 18 months ago presented with erosion of the ICD pocket with Pseudomonas bacteremia. For the past year, only multiple wound debridements were performed. Accordingly, we performed debridement and removal of the generator during this admission; however, bacteremia still persisted. Using transesophageal echocardiography, we detected vegetation on the pacing leads and tricuspid valve in the right atrium. We performed thoracotomy with tricuspid valve repair and pacing wire removal. However, anterior chest pain and refractory bacteremia occurred 3 months later after discharge, and an infectious foreign body in the wall of the innominate vein was detected using chest computer tomography. Thoracotomy was again performed for resection of the innominate vein with the infection source. Postoperative recovery was good, with no systemic infection or bacteremia. CONCLUSIONS: Pacing lead extraction is a common procedure following cardiac rhythm management device-related infection. However, residual foreign body-related bacteremia should be suspected in cases with fever of unknown origin after primary surgery. Preserving the innominate vein with patch repair is a feasible option. However, a postoperative 4-week course of antibiotics is recommended.

17.
J Cardiothorac Surg ; 11(1): 103, 2016 Jul 11.
Article En | MEDLINE | ID: mdl-27400685

BACKGROUND: Acute aortic syndrome, including classic aortic dissection, intramural aortic hematoma, and penetrating atherosclerotic ulcer (PAU), is a term used to describe a group of conditions with similar clinical symptoms, but with different pathophysiological mechanisms. PAU is a lesion that penetrates the internal elastic lamina through the media. It is usually located in the descending aorta and rarely observed in the ascending aorta. CASE PRESENTATION: A 76-year-old man with a history of essential hypertension was brought to the emergency department (ED) because of a sudden-onset chest pain at rest. He had not been taking his medication as ordered. His vital signs in the ED were a blood pressure of 82/60 mmHg, heart rate of 158 beats per min, respiratory rate of 22 breaths per min, and a body temperature of 37.2 °C. An electrocardiogram did not show an ST segment elevation, and cardiac enzymes were within normal limits. No widening mediastinum was found on chest radiography, but a large pericardial effusion with an impending cardiac tamponade was revealed on echocardiography. The diagnosis of PAU rupture in the ascending aorta with hemopericardium was made with chest computed tomography. An emergent sternotomy and ascending aorta reconstruction were performed. A ruptured ulcerative plaque through the intima to the adventitia without flap dissection in the ascending aorta was confirmed. The patient was discharged 18 days after the operation. CONCLUSIONS: Although PAU in the ascending aorta is uncommon, it is commonly lethal when it ruptures. With the current advances in endovascular techniques and devices, endovascular repair of PAU in the ascending aorta is currently recommended only for high-risk patients unsuitable for open repair. However, we anticipate that endovascular repair may become feasible in patients with PAU in the ascending aorta in the future.


Aorta/diagnostic imaging , Aortic Rupture/diagnostic imaging , Pericardial Effusion/surgery , Plaque, Atherosclerotic/diagnostic imaging , Ulcer/diagnostic imaging , Aged , Aorta/surgery , Aortic Rupture/surgery , Cardiac Tamponade/diagnostic imaging , Cardiac Tamponade/etiology , Cardiac Tamponade/surgery , Echocardiography , Humans , Male , Pericardial Effusion/diagnostic imaging , Pericardial Effusion/etiology , Plaque, Atherosclerotic/surgery , Tomography, X-Ray Computed , Ulcer/surgery
18.
Exp Biol Med (Maywood) ; 241(16): 1834-43, 2016 10.
Article En | MEDLINE | ID: mdl-27216599

Compared with conventional aortic cross-clamping, endovascular balloon occlusion (EBO) is a valuable strategy in unstable ruptured abdominal aorta aneurysm patients; however, it is unclear how long the balloon may remain safely inflated. Using a porcine model, we evaluated the influence of different EBO time periods on intra-abdominal pressure (IAP) and the association between various pathophysiologic indicators and reperfusion time. Twelve healthy three-month-old domestic piglets were subjected to ischemia/reperfusion injury using EBO within the abdominal aorta. Animals were grouped as A, B, and C based on 30, 60, or 120 min of ischemic time, respectively. Changes in IAP, hemodynamic data, respiratory and renal function, and histology after reperfusion were compared with baseline measurements. All pigs gradually developed intra-abdominal hypertension after ischemia/reperfusion injury. IAP increased significantly after 4 h of reperfusion in all three groups (all P < 0.001) with maximal IAP reaching > 22 mmHg in 10 pigs. However, no significant intergroup differences were found. Cardiac output remained stable, but mixed venous oxygen saturation decreased significantly at 4 h after reperfusion (P < 0.05). The pH decreased significantly at 10 min in all three groups (all P < 0.001). Histological changes in the small intestine, lung, and kidney occurred secondary to aortic ischemia; however, no significant differences were noted between groups (P > 0.05). EBO within the abdominal aorta induced ischemia/reperfusion injury which led to intra-abdominal hypertension, pathological changes within multiple organs, and decreased mixed venous oxygen saturation after only 30 min of abdominal aortic ischemia.


Balloon Occlusion/adverse effects , Reperfusion Injury/etiology , Animals , Aorta, Abdominal , Balloon Occlusion/methods , Disease Models, Animal , Female , Hemodynamics , Intra-Abdominal Hypertension/etiology , Male , Reperfusion Injury/pathology , Respiratory Function Tests , Swine
19.
Int J Radiat Oncol Biol Phys ; 95(1): 396-403, 2016 May 01.
Article En | MEDLINE | ID: mdl-27084657

PURPOSE: To investigate the efficacy and safety of fractionated boron neutron capture therapy (BNCT) for recurrent head and neck (H&N) cancer after photon radiation therapy. METHODS AND MATERIALS: In this prospective phase 1/2 trial, 2-fraction BNCT with intravenous L-boronophenylalanine (L-BPA, 400 mg/kg) was administered at a 28-day interval. Before each fraction, fluorine-18-labeled-BPA-positron emission tomography was conducted to determine the tumor/normal tissue ratio of an individual tumor. The prescription dose (D80) of 20 Gy-Eq per fraction was selected to cover 80% of the gross tumor volume by using a dose volume histogram, while minimizing the volume of oral mucosa receiving >10 Gy-Eq. Tumor responses and adverse effects were assessed using the Response Evaluation Criteria in Solid Tumors v1.1 and the Common Terminology Criteria for Adverse Events v3.0, respectively. RESULTS: Seventeen patients with a previous cumulative radiation dose of 63-165 Gy were enrolled. All but 2 participants received 2 fractions of BNCT. The median tumor/normal tissue ratio was 3.4 for the first fraction and 2.5 for the second, whereas the median D80 for the first and second fraction was 19.8 and 14.6 Gy-Eq, respectively. After a median follow-up period of 19.7 months (range, 5.2-52 mo), 6 participants exhibited a complete response and 6 exhibited a partial response. Regarding acute toxicity, 5 participants showed grade 3 mucositis and 1 participant showed grade 4 laryngeal edema and carotid hemorrhage. Regarding late toxicity, 2 participants exhibited grade 3 cranial neuropathy. Four of six participants (67%) receiving total D80 > 40 Gy-Eq had a complete response. Two-year overall survival was 47%. Two-year locoregional control was 28%. CONCLUSIONS: Our results suggested that 2-fraction BNCT with adaptive dose prescription was effective and safe in locally recurrent H&N cancer. Modifications to our protocol may yield more satisfactory results in the future.


Boron Neutron Capture Therapy/methods , Head and Neck Neoplasms/radiotherapy , Neoplasm Recurrence, Local/radiotherapy , Adult , Aged , Boron Compounds/therapeutic use , Boron Neutron Capture Therapy/adverse effects , Carotid Artery Diseases/etiology , Dose Fractionation, Radiation , Female , Follow-Up Studies , Head and Neck Neoplasms/mortality , Hemorrhage/etiology , Humans , Laryngeal Edema/etiology , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Phenylalanine/therapeutic use , Photons/therapeutic use , Prospective Studies , Stomatitis/etiology , Time Factors , Treatment Outcome
20.
Appl Radiat Isot ; 107: 312-316, 2016 Jan.
Article En | MEDLINE | ID: mdl-26595774

The neutron beam monitoring system is indispensable to BNCT facility in order to achieve an accurate patient dose delivery. The neutron beam monitoring of a reactor-based BNCT (RB-BNCT) facility can be implemented through the instrumentation and control system of a reactor provided that the reactor power level remains constant during reactor operation. However, since the neutron flux in reactor core is highly correlative to complicated reactor kinetics resulting from such as fuel depletion, poison production, and control blade movement, some extent of variation may occur in the spatial distribution of neutron flux in reactor core. Therefore, a dedicated neutron beam monitoring system is needed to be installed in the vicinity of the beam path close to the beam exit of the RB-BNCT facility, where it can measure the BNCT beam intensity as closely as possible and be free from the influence of the objects present around the beam exit. In this study, in order to demonstrate the importance of a dedicated BNCT neutron beam monitoring system, the signals originating from the two in-core neutron detectors installed at THOR were extracted and compared with the three dedicated neutron beam monitors of the THOR BNCT facility. The correlation of the readings between the in-core neutron detectors and the BNCT neutron beam monitors was established to evaluate the improvable quality of the beam intensity measurement inferred by the in-core neutron detectors. In 29 sampled intervals within 16 days of measurement, the fluctuations in the mean value of the normalized ratios between readings of the three BNCT neutron beam monitors lay within 0.2%. However, the normalized ratios of readings of the two in-core neutron detectors to one of the BNCT neutron beam monitors show great fluctuations of 5.9% and 17.5%, respectively.


Boron Neutron Capture Therapy/instrumentation , Radiation Monitoring/instrumentation , Boron Neutron Capture Therapy/standards , Equipment Design , Humans , Neutrons , Nuclear Reactors , Radiation Monitoring/standards , Radiometry/instrumentation
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