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Objective: to study the state of cognitive functions in children who were born and permanently live at radioactive contaminated territories (RCT) with pathology of the upper digestive tract, using pathopsychological testing; to increase the effectiveness of treatment and prophylactic measures aimed at preserving and restoring the health of RCT residents., Design, Patients and Methods: A randomized blind controlled clinical trial was conducted. There were examined, a total of 90 persons aged 6 to 17 years (35 boys and 55 girls) who were divided into two groups: the control group (I) included 30 persons of the conventional «clean» territories, and the main group (II) - 60 patients with patho- logy of the digestive organs who were born and live at the RCT. The study program included: the collection of anam- nesis, complaints; clinical and instrumental examinations. The following tests were applied by us: «What things are hidden in the drawings», Toulouse-Pieron, Raven, and Luria testing. For detecting the anxiety level, and the subjec- tive signs of autonomic dysfunctions were used the Spilberg-Hanin self-diagnosis and the Wein questionnaire, respectively., Results: It was shown that in children aged 6-11 years, according to the results of the Toulouse-Pieron test, speed of cognitive information-processing was significantly decreased by 7.17 conventional units, while on the back- ground of the etiopathogenetic treatment of the digestive tract - by 10.24 conventional units relative to the va- lues of the control group. The long-term memory was statistically significantly decreased in the examined children of senior school age (from 12 to 17 years). A significant increase in reactive anxiety and a reverse correlation between the personal anxiety (PA) and speed of cognitive information-processing (r = -0.331) were recorded in patients aged 6-11 years. In older patients, PA was increased.Сonclusions. The obtained results indicate that the state of cognitive functions was characterized by a decrease in speed of cognitive information-processing, long-term memory and a high level of anxiety in children aged from 6 to 17 years residents of RСT with pathology of digestive organs, according to the used testing., (L. M. Lisukha, I. Ye. Kolpakov.)

Internal exposure due to inhalation of aerosols depends on the ratio of aerodynamic shape factor (χ) to aerosol mass density (ρ). Inhaled aerosol parameters may differ from the default ρ and χ values provided by the International Commission on Radiological Protection, which are adopted for the assessment of internal exposures. This paper focuses on the influences of χ/ρ on the assessment of internal exposure to Pu for reference workers. Regional deposition fractions are found to decrease with increasing χ/ρ, and larger decreases are observed with smaller activity median aerodynamic diameter aerosols, while the slow clearance fractions (fs) in the tracheobronchial region are more sensitive for larger activity median aerodynamic diameter aerosols. Results from biokinetics calculations reveal that both the time-dependent content (excretion) and cumulative activities are determined mainly for particles initially deposited in the alveolar-interstitial region, while fs affects the local cumulative activities in the tracheobronchial region. χ/ρ is proven to have different influences for aerosols with different activity median aerodynamic diameters. The default χ/ρ values can be used when activity median aerodynamic diameters are greater than 1 μm, while one should pay attention to the value of χ/ρ when activity median aerodynamic diameters are less than 1 μm, where significant influence may be anticipated.

In July 2017, a medical accident occurred in South Korea, in which I-iodide solution was misadministered to the wrong patient. Although the International Commission on Radiological Protection provided internal dose coefficients for iodine for blocked thyroid, they were not reliable enough for determining the dose to the patient (whose thyroid uptake was incompletely blocked) due to a discrepancy in biokinetics. Therefore, a personalized dose assessment was performed to derive the individual-specific dose coefficients for the patient. Initially, the thyroid biokinetics of the patient were statistically clarified by fitting bioassay monitoring results and the corresponding predicted bioassay values, which were calculated repeatedly for varying iodine transfer rates in an iodine biokinetic model. After determining the transfer rate for the patient, the individual-specific dose coefficients were then calculated in accordance with latest recommendations of the International Commission on Radiological Protection. According to the individual-specific biokinetics, the 24 h thyroid uptake fraction of iodine was estimated as 0.52%. The thyroid absorbed dose of the patient was evaluated as 21.2 Gy, which differed greatly (by about 9 Gy) from the dose evaluated simply using the reference data for blocked thyroid uptake. The personalized dose assessment carried out for the patient not only reduced considerable uncertainties in the internal dose calculation, but also improved the reliability of the calculated internal dose by adopting the latest dosimetric data, including specific absorbed fraction values based on voxel phantoms. Through the dose assessment of the patient, the methodology of personalized dose assessment considering individual-specific biokinetics was developed.

Purpose: Limited pelvic nodal relapse of prostatic cancer is a paramount challenge for locoregional salvage treatments. Salvage whole pelvis radiation therapy as considered in the BLINDED trial is an attractive option, but there are concerns about its toxicity. This article describes early toxicity with the technique., Methods and Materials: BLINDED was a prospective multicenter phase 2 trial investigating high-dose salvage pelvic irradiation with an additional dose to the fluorocholine-based positron emission tomography-positive pelvic lymph nodes, combined with 6-month androgen blockade. The prescribed dose was 54 Gy in 1.8 Gy fractions with up to 66 Gy in 2.2 Gy fractions to the pathologic pelvic lymph nodes. Early toxicity was defined as toxicity until 1 year after radiation therapy. Patients quality of life was assessed using the European Organisation for Research and Treatment of Cancer questionnaires (QLQ-C30 and QLQ-PR25)., Results: Seventy-four patients were recruited in 15 French radiation oncology departments between August 2014 and July 2016. Seven were excluded before treatment because of violation of the inclusion criteria. The intention-to-treat analysis therefore included 67 patients. Half had received prior prostatic irradiation. Median age was 67.7 ± 6.5 years. Grade 2 acute urinary toxicity was observed in 9 of 67 patients (13.4%), and grade 2 1-year toxicity occurred in 4 of 67 patients (6%). Three patients (4.4%) had grade 3 urinary toxicity. Grade 2 acute digestive toxicity was observed in 10 of 67 patients (14.9%), and grade 2 1-year toxicity occurred in 4 of 67 patients (6%). Patients with prior prostate bed irradiation did not exhibit increased urinary or digestive toxicity. The European Organisation for Research and Treatment of Cancer questionnaire scores at 1 year did not worsen significantly., Conclusions: The acute and 1-year toxicity of the BLINDED protocol was satisfactory, even in patients with a history of prostatic irradiation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death, as few patients can be treated with currently available curative local modalities. In patients with HCC where curative modalities are not feasible, radiation therapy (RT) has emerged as an alternative or combination therapy. With the development of various technologies, RT has been increasingly used for the management of HCC. Among these advances, proton beam therapy (PBT) has several unique physical properties that give it a finite range in a distal direction, and thus no exit dose along the beam path. Therefore, PBT has dosimetric advantages compared with X-ray therapy for the treatment of HCC. Indeed, various reports in the literature have described the favorable clinical outcomes and improved safety of PBT for HCC patients compared with X-ray therapy. However, there are some technical issues regarding the use of PBT in HCC, including uncertainty of organ motion and inaccuracy during calculation of tissue density and beam range, all of which may reduce the robustness of a PBT treatment plan. In this review, we discuss the physical properties, current clinical data, technical issues, and future perspectives on PBT for the treatment of HCC.

Treatment and management of cancers in elderly patients require some special considerations. A better understanding of how cancers progress in those elderly patients who have not received any anticancer treatments could better help us in treating these patients and in making end-of-life decisions. Over the past years, we had encountered 57 elderly patients, aged 75 to 94 years (87.6 on average), with a cancer in the digestive system, who refused to accept anticancer treatment but who did receive the best available supportive and palliative care. Clinicopathological data of these patients were analyzed. Of these 57 cases, 49 were at an advanced or late stage, while the remaining eight were at an early stage at the time of diagnosis. The median overall survival time of all the patients was 11 months, and almost the entire cohort manifested multiple-organ impairments. The average number of malfunctioning organs per patient was 3.68. After carefully predicting, and then preventing or managing complications, only 54.4% of the patients eventually died of multiple-organ functional failure. Nearly 18% of the single organ dysfunctions were finally well-controlled. Our data provide the first statistical information on the survival time and the direct cause of death of the elderly patients with a cancer in the digestive system not treated with chemotherapy or other direct anticancer interventions, but who did receive the best available supportive and palliative cares. During their struggle with cancer, elderly patients clearly could benefit from prophylactic interventions on organ dysfunction.

It is not feasible to define very small or complex organs and tissues in the current voxel-type adult reference computational phantoms of the International Commission on Radiological Protection (ICRP), which limit dose coefficients for weakly penetrating radiations. To address the problem, the ICRP is converting the voxel-type reference phantoms into mesh-type phantoms. In the present study, as a part of the conversion project, the micrometer-thick target and source regions in the alimentary and respiratory tract systems as described in ICRP Publications 100 and 66 were included in the mesh-type ICRP reference adult male and female phantoms. In addition, realistic lung airway models were simulated to represent the bronchial (BB) and bronchiolar (bb) regions. The electron specific absorbed fraction (SAF) values for the alimentary and respiratory tract systems were then calculated and compared with the values calculated with the stylized models of ICRP Publications 100 and 66. The comparisons show generally good agreement for the oral cavity, oesophagus, and BB, whereas for the stomach, small intestine, large intestine, extrathoracic region, and bb, there are some differences (e.g. up to ~9 times in the large intestine). The difference is mainly due to anatomical difference in these organs between the realistic mesh-type phantoms and the simplified stylized models. The new alimentary and respiratory tract models in the mesh-type ICRP reference phantoms preserve the topology and dimensions of the voxel-type ICRP phantoms and provide more reliable SAF values than the simplified models adopted in previous ICRP Publications.

The internal dosimetry computer program internal dose assessment by computer (IDAC) for calculations of absorbed doses to organs and tissues as well as effective doses to patients from examinations with radiopharmaceuticals has been developed. The new version, IDAC2.0, incorporates the International Commission on Radiation Protection (ICRP)/ICRU computational adult male and female voxel phantoms and decay data from the ICRP publication 107. Instead of only 25 source and target regions, calculation can now be made with 63 source regions to 73 target regions. The major advantage of having the new phantom is that the calculations of the effective doses can be made with the latest tissue weighting factors of ICRP publication 103. IDAC2.0 uses the ICRP human alimentary tract (HAT) model for orally administrated activity and for excretion through the gastrointestinal tract and effective doses have been recalculated for radiopharmaceuticals that are orally administered. The results of the program are consistent with published data using the same specific absorption fractions and also compared with published data from the same computational phantoms but with segmentation of organs leading to another set of specific absorption fractions. The effective dose is recalculated for all the 34 radiopharmaceuticals that are administered orally and has been published by the ICRP. Using the new HAT model, new tissue weighting factors and the new adult computational voxel phantoms lead to an average effective dose of half of its earlier estimated value. The reduction mainly depends on electron transport simulations to walled organs and the transition from the stylised phantom with unrealistic interorgan distances to more realistic voxel phantoms., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Defecation allows the body to eliminate waste, an essential step in food processing for animal survival. In contrast to the extensive studies of feeding, its obligate counterpart, defecation, has received much less attention until recently. In this study, we report our characterizations of the defecation behavior of Drosophila larvae and its neural basis. Drosophila larvae display defecation cycles of stereotypic frequency, involving sequential contraction of hindgut and anal sphincter. The defecation behavior requires two groups of motor neurons that innervate hindgut and anal sphincter, respectively, and can excite gut muscles directly. These two groups of motor neurons fire sequentially with the same periodicity as the defecation behavior, as revealed by in vivo Ca(2+) imaging. Moreover, we identified a single mechanosensitive sensory neuron that innervates the anal slit and senses the opening of the intestine terminus. This anus sensory neuron relies on the TRP channel NOMPC but not on INACTIVE, NANCHUNG, or PIEZO for mechanotransduction.

Assessments of risk to a population group resulting from internal exposure to a particular radionuclide can be used to assess the reliability of the appropriate International Commission on Radiological Protection (ICRP) dose coefficient, E(50), used as a radiation protection device for the specified exposure pathway. An estimate of the uncertainty on the risk is important for informing judgements on reliability. This paper describes the application of parameter uncertainty analysis to quantify uncertainties resulting from internal exposures to radioisotopes of the alkaline earth metals, (90)Sr and (226)Ra, by members of the UK public. The study derives uncertainties in biokinetic model parameter values to calculate the distributions of the effective dose per unit intake using the ICRP Publication 60 formalism. The distributions are used to infer the uncertainty on the mean effective dose per unit intake to inform the derivation of uncertainty factors (UF) for the appropriate ICRP Publication 72 dose coefficients. Here, a UF indicates a 95 % probability that the best estimate of risk per unit intake is within a factor, UF, of the nominal risk associated with the appropriate ICRP dose coefficient, E(50), with respect to uncertainties in the biokinetic model parameter values. Ingestion: it is assumed that exposure occurs through the ingestion of radionuclides present in food and water. The results for both radionuclides suggest a UF of within 3 for all age groups, with median values close to the ICRP values. Inhalation: it is assumed that environmental exposure to radium occurs primarily due to insoluble forms present in fly ash discharged from coal-fired power stations; for strontium, exposure is assumed to occur due to residual aerosols produced as a result of atmospheric nuclear testing and nuclear reactor accidents. The results suggest a UF of around 3 and 6 for inhalation of (90)Sr and (226)Ra, respectively, by members of the public.

Measurements for internal dose assessment are required to be conducted based on the distribution of radionuclides in the body, which may change depending on the lapsed time. In this study, a biokinetic analysis code, which can be used in practical radiation control is developed, and the results of (60)Co and (137)Cs biokinetics are visualised as examples by drawing the depositions for each organ and tissue in a figure of the body as a function of lapsed time. In addition, based on visualised biokinetics, precautions for in vivo measurements are also discussed. These discussions led to the conclusion that the information of visualised biokinetics is useful for actual measurements in practical radiation control.

Aims: (1) Evaluate the dynamic of the depuration process of Crassostrea gigas oysters using different ultraviolet doses with different amounts of contaminants (virus, protozoa and organic contaminants) and (2) investigate the morphological changes in the oysters' tissues produced by the depuration procedures., Methods: The oysters were allocated in sites with different degrees of contamination and analyzed after 14 days. Some animals were used as positive controls by artificial bioaccumulation with HAdV2 and MNV1 and subjected to depuration assays using UV lamps (18 or 36 W) for 168 h. The following pollutants were researched in the naturally contaminated oysters, oysters after 14 days in sites and oysters during the depuration processes: virus (HAdV, HAV, HuNoV GI/GII and JCPyV), by (RT) qPCR; protozoa (Cryptosporidium and Giardia species), by immunomagnetic separation and immunofluorescence; and organic compounds (AHs, PAHs, LABs, PCBs and organochlorine pesticides-OCs), by chromatography. Changes in the oysters' tissues produced by the depuration processes were also evaluated using histochemical analysis by light microscopy. In the artificially bioaccumulated oysters, only HAdV2 and MNV1 were investigated by (RT) qPCR before the depuration procedures and after 96 and 168 h of these procedures., Results: At 14 days post-allocation, HAdV was found in all the sites (6.2 × 105 to 4.4 × 107 GC g(-1)), and Giardia species in only one site. Levels of PCBs and OCs in the oyster's tissues were below the detection limit for all samples. AHs (3.5 to 4.4 μg g(-1)), PAHs (11 to 191 ng g(-1)) and LABs (57 to 751 ng g(-1)) were detected in the samples from 3 sites. During the depuration assays, we found HAdV, Giardia and Cryptosporidium species until 168 h, independent of UV treatment. AHs, PAHs and LABs were found also after 168 h of depuration (36 W and without UV lamp). The depuration procedures did not produce changes in the oysters' tissues. In the artificially contaminated and depurated oysters, we detected HAdV until 168 h and MNV1 until 96 h of depuration., Conclusion: The applied depuration treatments were unable to eliminate the protozoa or to degrade the HAdV genomes but were able to degrade the MNV1 genomes. Similarly, the UV water treatment was not efficient for aliphatic hydrocarbons, PAHs and LABs, as their concentrations were equivalent or higher to the concentrations of the control samples and samples from depuration tanks without UV treatment., (© 2013.)

Cancer therapy has significantly improved in the past few decades with development of various newer classes of cytotoxic chemotherapy as well as novel, molecularly targeted chemotherapy. Similar to chemotherapy, radiotherapy is another important therapeutic option used in the curative and palliative management of various abdominal malignancies. However, both these treatments affect the tumor as well as the normal tissues, leading to significant toxicity. These side effects range from mild to life threatening, and may involve multiple organs. Imaging plays an important role in the early identification of such complications, which may allow more effective patient management. The aim of this article is to discuss and illustrate the wide spectrum of chemotherapy and radiotherapy induced complications in the abdomen and pelvis.

Purpose: To evaluate the safety and effectiveness of proton beam therapy for hepatocellular carcinoma (HCC) located adjacent to the alimentary tract., Patients and Methods: Forty-seven patients (median age, 69 years; range, 43-82 years) who had HCC located within 2 cm of the alimentary tract underwent proton beam therapy. Liver damage according to the Child-Pugh classification was Class A in 35 patients, Class B in 9, and Class C in 3. Treatment protocols of the early 16 patients and the late 31 patients were 72.6 GyE in 22 fractions and 77 GyE in 35 fractions, respectively., Results: During the median follow-up period of 23 months, 24 patients died; the remaining 23 patients were alive until September 2008. The median overall survival was 33.9 months (95% confidence interval [CI], 10.8-57.0 months). Actuarial overall and local progression-free survival rates at 3 years were 50.0% and 88.1%, respectively. Grade 2 and 3 alimentary tract hemorrhage was observed in 3 (6.4%) and 1 (2.1%) patients, respectively., Conclusions: Our proton beam therapy strategy for HCC located adjacent to the alimentary tract seems to be effective but should be performed with caution., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The increased production of nanotechnology materials is a potential source of nano-sized particles (NSPs) in aquatic ecosystems. Meanwhile, polycyclic aromatic hydrocarbons (PAHs), in the presence of ecologically relevant levels of ultraviolet radiation (UV), can be acutely toxic to aquatic species including fish and invertebrates. Considering that suspended carbon-based NSPs (e.g., C60 fullerenes) may act in similar ways as dissolved organic matter (DOM) by altering the bioavailability of PAHs, the objective of this research was to determine the effect of suspended C60 on the photo-induced toxicity of fluoranthene. Transmission electron microscopy indicated that the presence of C60 protected cellular components (e.g., mitochondria, microvilli, and basal infoldings) in organisms exposed to UV and fluoranthene phototoxicity in short-term exposures. However, we found that long-term exposure (21d) of low-level C60 caused significant cellular damage in the Daphnia magna alimentary canal. This paper highlights the importance of examining the interactions between existing stressors and nanoparticles in the aquatic environment., (Copyright 2009 Elsevier B.V. All rights reserved.)

Purpose: Ultraviolet radiation is a potent threat to the aquatic animals. Exposure to such stressor affects metabolic and immunological processes. The present investigation aims to study the effect of UV-B radiation on digestive enzymes and immunity of larvae of Catla catla., Materials and Methods: Larvae were exposed to ultraviolet-B (UV-B, 280-320 nm) radiation (145 microW/cm(2)) for three different exposure times of 5, 10 and 15 min on every other day. After 55 days, important digestive enzymes were assayed. For immunological study, lysozyme, glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels were measured. Then the fish were kept for one month without radiation and lysozyme level was measured., Results: Protein concentration varied directly with the duration of exposure and was highest among fish that had received the 15 min UV-B irradiation. Significantly higher amylase, protease, trypsin and chymotrypsin activities were found in 5 min exposed fish compared to others. Lysozyme level was significantly higher in control group compared to the UV-B treated fish. The lysozyme level decreased with the increasing duration of UV-B radiation. When fish were kept without UV-B radiation for one month, lysozyme level was brought to the normal level in all treatments, except 15 min exposed fish. The GOT and GPT levels were significantly higher in the 15 min exposed group than others., Conclusions: The effects of UV-B radiation on the digestive physiology and immune system of catla have been clearly observed in the present study. The decreased enzyme activities in UV-B radiated fish results into improper digestion and poor growth.

An experimental study was carried out in rabbits to investigate the effects of exposing rabbits to low-intensity pulsed magnetic fields (PMFs) on alimentary hyperlipemia. Thirty female white big ear rabbits were randomly divided into three groups. The normal group was fed with a standard chow diet and the other two groups (hyperlipid and magnetic) were fed with the chow diet supplemented with cholesterol, yolk powder and lard. The magnetic group was exposed to 15 Hz pulsed magnetic fields. After 8 weeks, levels of blood lipid and indices of hemorheology were examined. In addition, histomorphologic changes of hepatic and myocardial tissues were compared across the groups respectively. Compared with the hyperlipid group, hemorheology indices of the magnetic group reduced significantly from 12.80% to 38.05% (P < 0.01) indicating lower blood viscosity. Similarly, compared with the hyperlipid group, the levels of total cholesterol and triglycerides in the magnetic group decreased 40.52% and 52.42% (P < 0.01). On the contrary, high density lipoprotein (HDL) value obviously increased 66.67% (P < 0.01). Furthermore, compared with the control group, the values of triglycerides and HDL of the magnetic group did not show statistical differences (P > 0.05). The deposit of fatty material on the inner lining of thoracic aorta wall of the magnetic group was significantly lighter than that of the hyperlipid group. Numerous aggregation of lipoids emerged among myocardial myofibrils in the hyperlipid group, while no notable change was found in both the magnetic and control group. The results indicate that low-intensity PMFs could be helpful for the treatment of alimentary hyperlipemia., ((c) 2007 Wiley-Liss, Inc.)

Radiation-induced mucositis is a common and serious side effect of radiotherapy. Molecular mechanisms of mucosal injury, however, are still poorly understood and extremely difficult to study in humans. A novel Dark Agouti rat model using fractionated radiotherapy to induce mucositis has been developed to investigate the occurrence of alimentary mucosal injury. Twenty-four Dark Agouti rats were randomly assigned to receive either fractionated radiotherapy or no radiotherapy. The irradiated rats received a fractionated course of abdominal radiotherapy at 45 Gy/18 fractions/6 weeks treating thrice weekly (i.e., at a radiation dose of 2.5 Gy per fraction). After each week of radiation, a group of irradiated rats was killed. Histomorphology and mucin distribution in the alimentary tract was investigated. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was used to examine apoptosis in the colon and jejunum, and intestinal morphometry was used to assess villus length, crypt length, and mitotic crypt count. Immunohistochemistry of p53, nuclear factor-kappaB, cyclooxygenase (COX)-1, and COX-2 was also done. The fractionated radiotherapy course induced alimentary mucositis from week 1, with more severe injury seen in the small intestine. The hallmark appearance of apoptosis was present in the crypts of the small and large intestine. In the jejunum and colon, goblet cell disorganization and degeneration was obvious and crypt mitotic counts were severely depleted throughout the treatment. Expression of p53, nuclear factor-kappaB, COX-1, and COX-2 was increased in the irradiated intestinal sections. Fractionated radiation-induced alimentary mucositis has been effectively documented in the Dark Agouti rat for the first time. Further studies investigating the molecular mechanisms underlying radiation-induced mucositis are planned to ultimately achieve anti-mucotoxic-targeted therapies.

The Mediterranean fruit fly (medfly), Ceratitis capitata (Wiedemann), is a key pest of citrus in Spain because of significant yield losses and to quarantine restrictions. Biologically based control methods, such as the Sterile Insect Technique (SIT), which relies on the sterilization by irradiation of large numbers of insects, is gaining an increasing role in the control of medfly in Mediterranean areas. However, gamma-irradiation might damage the midgut epithelium cells, causing a lowering of nutritive assimilation that can negatively affect adult performance. Irradiation effects on digestive physiology are well established for a number of insect pests, but there is no information on medfly. Our aim was to determine the effects of gamma-irradiation on C. capitata digestive protease activity. Both larvae and adults were found to use a similar proteolytic system based on aspartyl-, trypsin-, chymotrypsin-, amino peptidase-, and carboxypeptidase A- and B-like activities. Pupae of the Vienna-7 (tsl) strain were irradiated at 70 or 140 Gy, two days before emergence, and the adults fed during 5 days on sugar-protein (4:1) diets. Protease activity was measured in midgut extracts and compared with males non-irradiated reared in the same conditions. The results showed that the irradiation doses tested had no effect on the digestive proteolytic activities of medfly adults. Moreover, the longevity of irradiated medflies at the highest dose (140 Gy) was similar to that of controls.

We present a new method of reporting the results of radiotherapy protocols. The dose-volume atlas of complication incidence is a comprehensive and unbiased summary of the dose-volume exposures and complications occurring in patients after treatment. This new tool provides clear and systematic information about the safety of regions of dose-volume exposure previously treated that can be used when considering new treatments. Actuarial and model-dependent versions of the atlas are described. By using the raw data in the appropriate forms of the atlas, logistic regression, Kaplan-Meier, and Cox proportional hazards analysis can be performed, allowing for the independent calculation of dose-volume response. The data required are simple enough that provided compatible definitions of dose, volume, and complications are used, atlases from different protocols are potentially additive, facilitating the meta-analysis of inter-interinstitutional data. If this method were adopted as a standard for reporting the outcome of treatment protocols, a potentially synergistic increase in the utility of each protocol could result.

Exposure to the magnetic field has remarkably increased lately due to fast urbanization and widely available magnetic field in diagnosis and treatment. However, biological effects of the magnetic field are not well recognized. The myoelectric activity recorded from the gastrointestinal and urinary systems is generated by specialized electrically active cells called interstitial cells of Cajal (ICCs). Thus it seems rational that ICC have significant vulnerability to physical factors like an electromagnetic field. The aim of this study was to evaluate the influence of pulsating electromagnetic field (PEMF) (frequency 10 kHz, 30ms, 300 muT burst, with frequency 1Hz) on ICCs density in the rat gastrointestinal tract. Rats were divided into two groups (n=32). The first group was exposed to PEMF continuously for 1, 2, 3, and 4 weeks (n = 16), and the second group (n=16) served as a control. Tissue samples of the rat stomach, duodenum and proximal colon were fixed and paraffin embedded. The tangential sections of 5 microm thickness were stained immunohistochemically with anti-c-Kit (sc-168) antibody and visualized finally by DAB as chromogen (brown end product). C-Kit positive branched ICC-like cells were detected under the light microscope, distinguished from the c-kit-negative non-branched smooth muscle cells and from the c-kit positive but non-branched mast cells and quantitatively analyzed by MultiScan computer program. Apoptosis detection was performed with rabbit anti-Bax polyclonal antibody (Calbiochem, Germany) and LSAB 2 visualization system. The surface of c-Kit immunopositive cells decreased after exposure to PEMF in each part of the gastrointestinal tract. Reduced density of ICCs was related to exposure time. The most sensitive to PEMF were ICCs in the fundus of the stomach and in the duodenum, less sensitive were ICCs in the colon and pacemaker areas of the stomach. No marked changes in ICC density in the pyloric part of the stomach were observed. We demonstrate that the PEMF induced apoptosis dependent decrease in ICC expression.

This paper considers doses from radon and decay products when inhaled or ingested by one year old infants and by ten year old children. Doses from decay products deposited on skin are also discussed. For inhalation and ingestion, the general pattern of doses to organs is broadly similar to that in adults. Much the largest doses are received by the organ of intake (respiratory tract and stomach respectively). Otherwise, tissues with higher fat content tend to receive somewhat higher doses from radon gas than other tissues. Dose coefficients (dose per unit intake factors) for children are generally larger than those for adults. However, total annual doses are more similar across the age groups because of smaller intakes of air and water by children. Radon decay products deposited on skin may be able to induce skin cancer. However, the location of the sensitive cells is not known with certainty and they may lie too deep to receive significant dose. If they are irradiated, it is likely that doses to children would be larger than for adults. The radiological significance of doses to children is discussed.

Objectives: To analyze the effects of the B-mode ultrasound acquisition and targeting (BAT) system for positioning of patients with prostate cancer receiving intensity-modulated radiotherapy on acute gastrointestinal (GI) and genitourinary (GU) toxicity., Methods: The records of 50 consecutive patients treated using the BAT system were reviewed. Additionally, a comparison (no-BAT) group (ie, a group without a BAT study) treated in a similar manner was identified. The no-BAT group consisted of 49 patients treated immediately before the BAT group. For the two groups, the target definitions and dose prescriptions were identical, the treatment plan acceptance criteria were identical, and intensity-modulated radiotherapy was used for all patients. The daily BAT movements were charted in each of the three principal directions. Acute toxicity was scored for all patients according to the Radiation Therapy Oncology Group GI and GU acute toxicity scales., Results: The GU toxicity rates for the BAT versus no-BAT groups were grade 0 in 20% versus 14%; grade 1 in 38% versus 47%; grade 2 in 38% versus 39%; and grade 3 in 4% versus 0%, respectively (P = 0.284). The corresponding GI toxicity rates were grade 0 in 42% versus 27%; grade 1 in 28% versus 29%; and grade 2 in 30% versus 45% (P = 0.040). The incidence of GU and GI toxicity did not correlate with the directions or size of the BAT moves. Regression analysis revealed that for acute GI toxicity, the only variable reaching statistical significance was BAT use; no variable, including BAT use, reached statistical significance for acute GU toxicity., Conclusions: The use of the BAT system did not change the rate of acute GU toxicity but did reduce the rate of acute GI toxicity.

Background and Purpose: The recent RTOG guidelines for future clinical developments in gynecologic malignancies included the investigation of dose escalation in the paraaortic (PO) region which is, however, very difficult to target due to the presence of critical organs such as kidneys, liver, spinal cord, and digestive structures. The aim of this study was to investigate intensity-modulated radiotherapy's (IMRT) possibilites of either increasing, in a safe way, the dose to 50-60 Gy in case of macroscopic disease or decreasing the dose to organs at risk (OR) when treatment is given in an adjuvant setting., Material and Methods: The dosimetric charts of 14 patients irradiated to the PO region at the Department of Radiation Oncology, University Hospital of Liege, Belgium, in 2000 were analyzed in order to compare six-field conformal external-beam radiotherapy (CEBR) and five-beam IMRT approaches. Both CEBR and IMRT investigations were planned to theoretically deliver 60 Gy to the PO region in the safest way possible. Dose-volume histograms (DVHs) were calculated for clinical target volume (CTV), planning target volume (PTV), and OR. Student's t-test was used to compare the paired DVH data issued from CEBR and IMRT planning., Results: The IMRT approach allowed to cover the PTV at a higher level as compared to CEBR. Using IMRT, the maximal dose to the spinal cord was reduced from 42.5 Gy to 26.2 Gy in comparison with CEBR (p < 0.00001). Doses to the kidneys were significantly reduced, with < 20% receiving >or= 20 Gy in the IMRT approach (p < 0.00001). Irradiation of digestive structures was not different, with < 25% receiving 35 Gy. Doses to the liver remained low regardless of the method used., Conclusion: At 60 Gy, IMRT is largely sparing the spinal cord and kidneys as compared to CEBR and represents an interesting approach not only for dose escalation up to 50-60 Gy (probably facilitating the radiochemotherapy approaches) but also in an adjuvant setting at lower doses. The dosimetric data of this study are in the same range as those published recently with a dynamic arc conformal approach.

Ionizing radiation (IR) induces p53-dependent apoptosis in radiosensitive tissues, suggesting that p53 is a determinant of radiation syndromes. In fact, p53-deficient mice survive doses of IR that cause lethal hematopoietic syndrome in wild-type animals. Surprisingly, p53 deficiency results in sensitization of mice to higher doses of IR, causing lethal gastro-intestinal (GI) syndrome. While cells in the crypts of p53-wild-type epithelium undergo prolonged growth arrest after irradiation, continuous cell proliferation ongoing in p53-deficient epithelium correlates with accelerated death of damaged cells followed by rapid destruction of villi and accelerated lethality. p21-deficient mice are also characterized by increased sensitivity to GI syndrome-inducing doses of IR. We conclude that p53/p21-mediated growth arrest plays a protective role in the epithelium of small intestine after severe doses of IR. Pharmacological inhibition of p53 by a small molecule that can rescue from lethal hematopoietic syndrome has no effect on the lethality from gastro-intestinal syndrome, presumably because of a temporary and reversible nature of its action., (Copyright 2004 Nature Publishing Group)

Purpose: - To report our experience on treatment planning and acute toxicity in 16 patients suffering from clinically localized prostate cancer treated with high-dose intensity-modulated radiation therapy (IMRT)., Patients and Methods: - Between March 2001 and October 2002, 16 patients with clinically localized prostate cancer were treated with IMRT. Treatment planning included an inverse-planning approach, and the desired beam intensity profiles were delivered by dynamic multileaf collimation. All patients received the entire treatment course with IMRT to a prescribed dose of 78 Gy. All IMRT treatment plans were compared with a theoretical conventional three-dimensional conformal radiation therapy (3D-CRT). Acute lower gastro-intestinal (GI) and genito-urinary (GU) toxicity was evaluated in all patients and graded according to the Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE v. 3.0). A relationship between dose volume and clinical toxicity was evaluated., Results: - Ninety-five percent of the PTV2 received more than 76 Gy using IMRT or 3D-CRT with no difference between both methods. The dose-volume histogram mean obtained for the PTV2 was not different between IMRT and 3D-CRT. IMRT improved homogeneity of the delivered dose to the PTV2 as compared with 3D-CRT (7.5 vs 9%, respectively). Ninety-five percent of the PTV1 received 5 Gy more using IMRT with protection of the bladder and the rectum walls. The benefit was considered below 75 and 70 Gy for the wall of the bladder and the rectum, respectively. Grade 2 GI and GU toxicity was observed in four (25%) and five (31%) patients, respectively. No grade 3 toxicity was observed. There was a trend towards a relationship between the mean rectal dose and acute rectal toxicity but without statistical significant difference (P =0.09)., Conclusion: - Dose escalation with IMRT is feasible with no grade 3 or higher acute GI or GU toxicity. Examination of a larger cohort and longer-term follow-up are warranted in the future.

Recently developed biokinetic models of ICRP permit increasingly realistic descriptions of the behaviour of radionuclides in the human body. This, however, has made the interpretation of bioassay data extremely difficult. Thus computer programs for implementing these models are in need, but very few are available. The present work describes personal-computer-based software, MONDAL2 (monitoring to dose calculation ver. 2), that enables users to estimate intake activity and the resulting effective doses from bioassay measurements for both workers and members of the public. This software runs on Microsoft Windows 95, 98, Millennium edition, 2000 or XP. If the system is to be fully copied to a hard disk, hard disk space of 23 MB is required. This software is distributed by the National Institute of Radiological Sciences free of charge., (Copyright 2004 Oxford University Press)

Randomised studies in locally advanced cervical cancer patients showed that cisplatin should be given concurrently with radiotherapy, because of a better long-term survival compared to radiotherapy alone. This increases the relevance of treatment related toxicity. This review summarises the acute and long-term toxicity of radiotherapy given with or without chemotherapy for cervical cancer. Acute toxicity (all grades) of radiotherapy is reported in 61% of the patients in the rectosigmoid, in 27% as urological, in 27% as skin and in 20% as gynaecological toxicity. Moderate and severe morbidity consists of 5% to 7% gastrointestinal and 1% to 4% genitourinary toxicity. Adding chemotherapy to radiotherapy increases acute haematological toxicity to 5% to 37% of the patients and nausea and vomiting in 12% to 14%. Late effects of radiotherapy include gastrointestinal, urological, female reproductive tract, skeletal and vascular toxicity, secondary malignancies and quality of life issues. For at least 20 years after treatment, new side effects may develop. Gastrointestinal toxicity usually occurs in the first 2 years after treatment in about 10% of the patients. The incidence of moderate and severe urological toxicity can increase up to 10% and rises over time. Gynaecological toxicity usually occurs shortly after treatment while skeletal and vascular toxicity can occur years to decades later. Thus far, no increase in late toxicity has been observed after the addition of cisplatin to radiotherapy. Finally, methods to prevent or decrease late toxicity and therapeutical options are discussed. However, most randomised studies still have a limited follow-up period.

Much experimental evidence has been accumulated assessing the tolerance of various tissues to IORT, and much of the tolerance data have resulted from the use of canine models. Guidelines of IORT tissue tolerance established in experimental models have been used in the clinical application of IORT at numerous institutions. Although the radiotolerance of differing tissues can vary among species, sufficient clinical experience has accumulated to validate the canine tissue tolerance model as representative of human tissue responses to IORT. Cellular effects from radiation principally stem from direct damage to DNA, and thus proliferating tissues are among the most radiosensitive, with arrested or abnormal cell division. These tissues can manifest striking early toxicity, reflecting the rate of cell division that is affected by the radiation. Irradiation of nonproliferating or slowly proliferating tissues may show little or no early toxicity, but late effects can be manifested to considerable and varying degrees. In much of this late toxicity, pathologic changes develop from progressive ischemia, brought about by the gradual obliteration of small blood vessels. Irradiated endothelium often becomes replaced by a thickened fibrous layer, which, in small vessels, leads to occlusion and ischemic necrotic changes in the supplied tissue. In larger vessels, fibrosis can lead to wall weakening and aneurysmal dilatation, rupture, or thrombosis. The common denominator, then, of radiation damage to many tissues is related to vascular effects. Although the tolerance to IORT-induced toxicity can vary considerably among tissues, doses ranging to 25 Gy can generally be tolerated without significant toxicity. Vital areas where IORT dose must be carefully monitored include critical vasculature, gastrointestinal viscera, ureter, significant motor or sensory nerve trunks, and central nervous system structures. Higher doses can generally be delivered safely to anatomic areas at risk for tumor that are at a distance from sensitive organs or tissues. The general principle providing the rationale of IORT should always be practiced: maximize the radiation dose to the tumor and tumor-harboring tissues while minimizing dose exposure to surrounding normal tissues.

Purpose: To provide a preliminary analysis of chronic gastrointestinal (GI) toxicity in gynecology patients treated with intensity-modulated whole pelvic radiation therapy (IM-WPRT)., Methods and Materials: Between February 2000 and August 2001, 36 gynecology patients received IM-WPRT. All patients underwent a contrast-enhanced computed tomography scan, and a clinical target volume (CTV) was contoured consisting of the upper vagina, parametria, uterus (if present), and presacral and pelvic lymph node regions. The CTV was expanded by 1 cm to create a planning target volume (PTV). Seven or 9-field IM-WPRT plans were generated. IM-WPRT plans were highly conformal, providing excellent coverage of the PTV and considerable sparing of normal tissues, including the small bowel and rectum. Chronic GI toxicity was scored: 0 (no symptoms), 1 (mild symptoms, no medications required), 2 (moderate symptoms, medications required), and 3 (severe symptoms, hospitalization, surgery required). Chronic GI toxicity in 30 gynecology patients treated with conventional WPRT patients before the implementation of IM-WPRT was also evaluated. Median follow-up in the IM-WPRT and WPRT groups were 19.6 and 30.2 months, respectively., Results: The IM-WPRT and WPRT groups were well balanced in terms of most patient and treatment factors, including age, site, stage, chemotherapy, WPRT dose, and brachytherapy, except for a higher frequency of surgery (75 vs. 54%, p = 0.02) in the IM-WPRT group. Overall, IM-WPRT patients had a lower rate of chronic GI toxicity (11.1 vs. 50.0%, p = 0.001) than WPRT patients. The percentage of IM-WPRT patients with Grade 1, 2, and 3 toxicity were 8.3%, 2.8%, and 0%, respectively. Corresponding percentages in the WPRT group were 30.0%, 16.7%, and 3.3%, respectively. The only other factor correlated with chronic GI toxicity was age (p = 0.02). On multivariate (logistic regression) analysis controlling for age and other clinical factors, IM-WPRT retained its statistical significance (p = 0.01; odds ratio 0.16; 95% confidence interval 0.04, 0.67), Conclusions: Our results suggest that IM-WPRT is associated with less chronic GI toxicity than conventional WPRT in patients with gynecologic malignancies. However, longer follow-up and more patients are clearly needed to ascertain whether the benefits of IM-WPRT treatment seen here translate into true long-term reductions in chronic GI toxicity.

Assessment of organ doses from internally deposited radionuclides involves the use of predetermined specific absorbed fractions (SAFs). Many tabulations of SAFs have been derived from Monte Carlo transport simulations using stylized computational models that are not fully realistic of human internal organ anatomy. This paper presents the results of a study to calculate SAFs in the gastrointestinal (GI) tract using a recently developed tomographic model VIP-Man and the EGS4 Monte Carlo radiation transport code. Results show that, for some energies and source-target combinations, considerable discrepancies exist between these results and those from earlier studies, suggesting a need to evaluate existing data carefully by comparison with realistic models.

Objectives: To review the efficacy of salvage radiotherapy (RT), to treat elevated prostate-specific antigen (PSA) levels for presumed local recurrence of prostatic adenocarcinoma after retropubic prostatectomy, and identify the factors that may predict for successful treatment., Methods: Fifty-one patients with hormonally naive pT2-3N0-1M0 prostate cancer were treated with RT for locally persistent or recurrent disease. The patients received a median dose of 65.7 Gy (range 61.2 to 72.3) to the prostate bed. Successfully treated patients had undetectable PSA levels; the endpoint of the study was biochemical failure., Results: The median follow-up was 3.8 years; 42 of 51 patients had at least 2 years of follow-up. Twenty-three patients (45%) were biochemically free of disease. The estimated biochemically free of disease rate at 3 and 5 years was 56% and 16%, respectively. Whether the patients were treated for persistently elevated PSA levels or for rising PSA levels from undetectable levels after retropubic prostatectomy, their PSA values were equally likely to drop to undetectable levels (65%). Univariate analysis demonstrated two factors that significantly predicted for successful salvage treatment: the absence of seminal vesicle invasion and the absence of lymphovascular invasion. A pretreatment PSA level less than 0.425 ng/mL trended toward statistical significance (P = 0.059). Only seminal vesicle invasion maintained significance on multivariate analysis. The RT was well tolerated, and the gastrointestinal and genitourinary toxicity was largely Radiation Therapy Oncology Group grade 1., Conclusions: Salvage RT is moderately effective in treating patients with locally persistent or recurrent prostate adenocarcinoma. Seminal vesicle invasion and lymphovascular invasion predicted for unsuccessful treatment.

Background: Radiotherapy-induced side effects are often scored retrospectively according to the EORTC/RTOG scores for organs at risk by reviewing the medical records. Some studies could prove an over- or underestimation of side effects as assessed by the medical professionals. The aim of this study was to prospectively evaluate differences in side effects as described by the doctors and the patients., Patients and Methods: 47 patients with prostate cancer were questioned about their side effects by a radiotherapist and asked to fill in a questionnaire at the start, in the middle and at the end of radiotherapy. The data of this questionnaire and the doctor's report were scored according to the German version of the EORTC/RTOG scores for gastrointestinal (GI) and genitourinary (GU) side effects and subsequently compared. We distinguished between "moderate" disagreement (better/worse by one grade, assessed by the doctor) and "pronounced" disagreement (better/worse by two grades, assessed by the doctor)., Results: The number of GI and GU side effects increased during radiotherapy both according to data obtained from the doctor and the patient questionnaire. Comparing doctors' reports with patients' questionnaires, for GI side effects an agreement was found in 22/47 patients, "moderately better" scores by the doctor's report were found in 13/47 patients, and "moderately worse" scores in 9/47 patients on average. "Pronouncedly better and worse" scores were found in 2/47 patients. For GU side effects an agreement was seen in 22/47 patients, "moderately better" scores in 17/47 patients and "moderately worse" scores in 3/47 patients. Regarding GU side effects, only pronouncedly better scores, as assessed by the doctor, were found in a mean of 4/47 patients. If the EORTC/RTOG score is used in its original English version, a difference is found, particularly in the assessment of GU side effects, resulting in an higher amount of agreement concerning GU side effects and a minor amount of "pronounced disagreement"., Conclusion: In order to evaluate radiation-induced side effects, a patient's self-reported questionnaire should be included in the analysis of morbidity, above all for grade 0, 1, and 2 side effects. The validity of data seems to be questionable, particularly in the assessment of grade 0, 1 and 2 side effects, if only data from the doctors' reports are taken into account. The German version of the EORTC/RTOG score--not including the pretreatment status--leads to different results, particularly in the assessment of grade 0, 1, and 2 urinary side effects, which asks for a revision.

The purpose of this study was to assess the radiation exposure of patients in several standard protocols in multi-slice CT (MSCT). Scanning protocols for neck, chest, abdomen, and spine were examined on a Somatom Plus 4 Volume Zoom MSCT (Siemens, Erlangen, Germany) with changing slice collimation (4x1, 4x2.5, and 4x5 mm), and pitch factors (1, 1.5, and 2). Effective doses were calculated from LiF-TLD measurements at several organ sites using an Alderson-Rando phantom and compared with calculations using the weighted CTDI. Effective dose for MSCT of the neck was 2.8 mSv. For different protocols for MSCT of the chest, 7.5-12.9 mSv were found. In abdominal MSCT protocols, effective dose varied between 12.4 and 16.1 mSv. The MSCT of the spine may lead to 12 mSv. An excellent correlation between the effective dose as determined by LiF-TLD and the calculated effective dose using the weighted CTDI could be demonstrated; however, a difference of up to 30% (mean 14.3%) was noted. Standard protocols for MSCT as measured in this study showed effective doses of up to16 mSv. Phantom measurement data show a good correlation to estimations using the weighted CTDI.

Purpose: To describe the frequency and magnitude of late GI and GU morbidity in prostate cancer patients treated to high dose levels with a simple three-dimensional conformal technique., Methods and Materials: A total of 156 intermediate- and high-risk patients were treated between January 1, 1992 and February 28, 1999 with a simple four-field three-dimensional conformal technique to 79-84 Gy. All patients were treated with a four-field conformal technique; the prostate received 82 Gy and the seminal vesicles and periprostatic tissue 46 Gy. GI and GU toxicity was scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Morbidity Grading Scale and compared using Kaplan-Meier estimates., Results: The late Grade 2 GI complication rate was 9% and 38% at 3 years for patients treated with and without rectal blocking, respectively (p = 0.0004). No Grade 3 late GI complications developed. The rate of Grade 2 late GU complications was 5%, 8%, and 12% at 12, 24, and 36 months, respectively. The Grade 3 late GU complication rate was 2% at 36 months. These differences were not statistically significant., Conclusion: The treatment method described is a simple four-field conformal technique that can be easily implemented in the general radiation community. A dose of 79-84 Gy can be safely delivered to the prostate, with a 9% rate of late Grade 2 GI, 12% rate of late Grade 2 GU, and 2% rate of late Grade 3 GU complications.

This paper discusses the doses from radon and from its short-lived decay products to a number of organs and tissues and to the foetus. The aim is to put all these doses into context rather than concentrating only on the largest contributions. There is also a brief discussion of the evidence from epidemiology on the risks of exposure to radon and its decay products. As is well known, under normal circumstances the greatest hazard is to the respiratory tract from inhalation of radon decay products. Radon decay products may also give substantial doses to skin. Under some circumstances it seems likely that ingested radon could give significant doses to the stomach. Other risks appear to be smaller; the results given here allow them to be compared.

Purpose: Although hyperthermia has been used for more than two decades in the treatment of pelvic tumors, little is known about the potential impact of heat on rectal toxicity when combined with other treatment modalities. Because rectal toxicity is a concern with radiation and may be exacerbated by hyperthermia, definition of the association of thermal dose parameters with rectal toxicity is important. In this report, we correlate rectal toxicity with thermal dose parameters for patients treated with hyperthermia and radiation for prostate cancer., Methods and Materials: Thirty patients with T2b-T3b disease (1992 American Joint Committee On Cancer criteria) enrolled in a Phase II study of external beam radiation +/- androgen-suppressive therapy with two transrectal ultrasound hyperthermia treatments were assessed for rectal toxicity. Prostatic and anterior rectal wall temperatures were monitored for all treatments. Rectal wall temperatures were limited to 40 degrees C in 19 patients, 41 degrees C in 3 patients, and 42 degrees C in 8 patients. Logistic regression was used to estimate the log hazard of developing National Cancer Institute Common Toxicity Criteria Grade 2 toxicity based on temperature parameters. The following were calculated: hazard ratios, 95% confidence intervals, p values for statistical significance of each parameter, and proportion of variability explained for each parameter., Results: Gastrointestinal toxicity was limited to Grade 2. The rate of acute Grade 2 proctitis was greater for patients with an allowable rectal wall temperature of >40 degrees C. In this group, 7 of 11 patients experienced acute Grade 2 proctitis, as opposed to 3 of 19 patients in the group with rectal wall temperatures limited to 40 degrees C (p = 0.004). Preliminary assessment of long-term toxicity revealed no differences in toxicity. Hazard ratios for acute Grade 2 proctitis for allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax were 9.33 (p = 0.01), 3.66 (p = 0.03), and 2.29 (p = 0.08), respectively. A model combining these three parameters explained 48.6% of the variability among groups., Conclusion: Rectal toxicity correlates with maximum allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax for patients undergoing transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer. Further definition of this association of thermal dose parameters with rectal toxicity in treatment of pelvic malignancies with hyperthermia should advance the goal of delivering thermal therapy in an effective yet safe manner.

Foreign body ingestions are a frequent occurrence, a common presentation at emergency departments, but long, pointed-end metallic spoon swallowing is an uncommon occurrence. Unlike most cases of foreign-body ingestion, there have been no cases of spontaneous passage reported. Consequently, prompt removal is recommended before complications develop. We report a case of accidental ingestion of a long, pointed metallic spoon which failed to pass through the gastrointestinal tract and be excreted. This patient was managed successfully with gastrotomy to remove the object. We recommend this approach for the removal of long pointed foreign bodies to avoid complications developing.

Ionizing radiation from all sources under appropriate conditions leads to cell death and tissue damage. It is used in cancer treatment under the assumption of a higher radiosensitivity of the fast dividing tumor cells as compared with adjacent host tissues. The radiosensitivities of proliferating host tissues like bone marrow and gastrointestinal lining epithelium are dose limiting. Since these host tissues and many tumors show circadian and other periodicities in their cell proliferation, the timing of radiation treatment according to host and/or tumor rhythms is expected to improve the toxic/therapeutic ratio of the treatment. The experimental data on the chronobiology of radiation exposure show circadian rhythmicity in radiation response after whole body irradiation in mice and rats with highest toxicity in light-dark 12h:12h synchronized animals during their daily activity span. Bone marrow toxicity as well as gastrointestinal epithelial damage show circadian rhythms in part due to radiation damage to the stem cells involved and especially in the intestine also due to damage to the microvasculature. Chronoradiotherapy of malignant tumors seems promising, alone or in combination with response modifiers, provided the host and potential tumor rhythms can be monitored.

Changes in leukocyte counts and in the gut microflora of laboratory rats irradiated with single whole-body dose of gamma rays (5.0 Gy) were determined. The number of leukocytes was lower especially 1 and 2 weeks after irradiation. A significant decrease in lymphocytes was observed 1 week and in monocytes 1 and 2 weeks after irradiation. In parallel with these changes, an increase in common microflora was observed; some microorganisms, which normally are not present in duodenum, liver and mouth cavity, were detected in these organs.

Unconventional, more aggressive irradiation protocols are usually associated with aggravation of acute reactions. In recent clinical studies, this has resulted in modulation of late effects in the same organ. This phenomenon has been termed consequential late effect (CLE). Correlations between acute and late effects have been reported in a number of tissues. Moreover, some radiobiological parameters may be used to differentiate between consequential and generic late effects: Dose fractionation and overall treatment time have a similar effect on acute and consequential responses, but opposing effects on generic late effects. Modulation of acute effects will affect the consequential component of late sequelae. Similarly, it will be influenced by the irradiated volume if a volume effect exists for the acute response. Moreover, markers for the acute response should be predictive for consequential effects. The present review gives preclinical and clinical evidence for CLE. These are predominantly found in organ systems where the acute response (of the epithelial lining) is associated with an impairment of the barrier against mechanical or chemical stress, which may cause additional trauma to the underlying tissues. Therefore, CLE are mainly found in the urinary and intestinal system, in mucosa and, to some extent, in skin. In these tissues with a consequential component of the late sequelae, amelioration of the acute response to irradiation may be a useful approach to minimize late side effects of effective radiation therapy.

Radiation induced gastrointestinal damage occurs due to the destruction of the clonogenic crypt cells and eventual depopulation and denudation of the villi. P. hexandrum, a plant, known for its antitumour activity, has been shown to protect the mice against whole body lethal (10 Gy) irradiation. Present study was undertaken to investigate the radioprotective effect of P. hexandrum on jejunal villi cells, crypt cells, their proliferative capacity and mitigation of apoptosis. In an in vivo micro colony survival assay, pre-irradiation administration of P. hexandrum (-2 h) increased the number of surviving crypts in the jejunum by a factor of 3.0 (P < 0.05) and villi cellularity by 2.7 (P < 0.05) fold in comparison to irradiated control. Pre-irradiation administration of P. hexandrum reduced the incidence of apoptotic bodies in the crypts (P < 0.05) in a time dependent manner and depicted a mitotic arrest till the 24 h. However, after 84 h the percentage of mitosis was observed to be nearly similar to that of unirradiated control. This study suggests that arrest of cell division may help in protecting the clonogenic cells against radiation. It would be interesting to investigate further the role of P hexandrum in influencing various cell cycle regulators like bcl-2, TGF-beta, Cyclin-E etc.

A new method is described for calculating radiation doses to benthic invertebrates from radionuclide concentrations in freshwater sediment. Both internal and external radiation doses were estimated for all 14 principal radionuclides of the uranium-238 decay series. Sediments were collected from three sites downstream of a uranium mining operation in northern Saskatchewan, Canada. Sediments from two sites, located approximately 1.6 and 4.4 km downstream from mining operations, yielded absorbed doses to both larval midges, Chironomus tentans, and adult amphipods, Hyalella azteca, of 59-60 and 19 mGy/year, respectively, compared to 3.2 mGy/year for a nearby control site. External beta radiation from protactinium-234 (234Pa) and alpha radiation from uranium (U) contributed most of the dose at the impacted sites, whereas polonium-210 (210Po) was most important at the control site. If a weighting factor of 20 was employed for the greater biological effect of alpha vs. beta and gamma radiation, then total equivalent doses rose to 540-560 mGy/year at the site closest to uranium operations. Such equivalent doses are above the 360-mGy/year no-observed-effect level for reproductive effects in vertebrates from gamma radiation exposure. Data are not available to determine the effect of such doses on benthic organisms, but they are high enough to warrant concern. Detrimental effects have been observed in H. azteca at similar uranium concentration in laboratory toxicity tests, but it remains unclear whether the radiotoxicity or the chemotoxicity of uranium is responsible for these effects.

Patient A who was exposed to a critical dose of radiation developed skin lesions throughout the body surface, gastrointestinal disorder with massive diarrhea and prominent bleeding, which caused severe loss in body fluids. Gastrointestinal bleeding due to the deteriorated intestinal mucosa was considered to be one of the major causes of death, although infection did not develop, possibly because of SDD and aseptic intensive care, until terminal stages. Patient A ultimately developed respiratory and renal failure in addition to skin exudate and gastrointestinal bleeding, and died of multiple organ failure on the 83rd day after exposure. The extreme unevenness of the dose distribution and the neutron versus y-ray component made the clinical manifestation very complicated. Initially, the mean absorbed dose was calculated as 16-20 GyEq for Patient A, mainly based on neutron-activated 24Na in the blood. However, a very recent calculation showed that the absorbed skin dose was highest at the upper-right abdomen reaching 61.8 Gy (27.0 as neutron plus 34.8 Gy as y-ray). The dorsal side was calculated to have received one eighth of the value of the abdominal side, and much smaller neutron component. His absorbed-dose distribution throughout the body was very inhomogeneous because of the closeness of the standing point to the mixing tank. Despite prolonged survival because of intensive care with massive fluids and blood transfusion, peripheral blood stem-cell transplantation, cultured skin-cell grafts, and the administration of cytokines for marrow, the patient was not saved. Restoration of the bone marrow function, prevention of skin fibrosis, radiation lung damage, and repair of gastrointestinal mucosa, and final recovery of the patient were elusive. Abundant personnel and resources were also a prerequisite to allow for the comprehensive and collective intensive care. A further understanding of the effects of high-dose radiation as well as the basic and clinical development of regeneration medicine are important issues for the future.

Ionising radiation exposure occurs during radiotherapy, diagnostic tests or by accident. In all cases the gastrointestinal tract, which is highly sensitive to radiation, may be at risk. Each region may respond differently to radiation exposure which to some extent is reflected by clinical symptoms. The evaluation of injury, whether acute or chronic, depends on the utilization of a variety of techniques. It appears that no definitive tests exist and that a multiparametric analysis should be undertaken. This review addresses the question of accessible markers associated with radiation-induced intestinal pathologies. Several approaches are discussed which include clinical observations, measurement of faecal parameters, changes in inflammatory mediators and possible applications of imaging techniques.

Purpose: To report acute toxicity and to evaluate the relationship between dose-volume effects and acute toxicity in patients with localized prostate cancer, treated with intensity-modulated radiation therapy (IMRT)., Methods and Materials: Acute toxicity (both lower gastrointestinal [GI] and genito-urinary [GU]) in 100 patients treated with IMRT definitively to a prescribed dose of 70 Gy were assessed using RTOG scoring criteria. A rectal balloon was used for prostate immobilization. Mean doses to seminal vesicles, prostate, bladder, and rectum were recorded. Average irradiated bladder and rectal volumes above 65, 70, and 75 Gy were assessed. A relationship between dose volume and clinical toxicity was evaluated. All patients completed the full duration of acute toxicity assessment., Results: Mean doses to the prostate and seminal vesicles were 75.8 and 73.9 Gy. This represents a moderate dose escalation. Acute GI toxicity profile was very favorable. Eleven percent and 6% of the patients had grade 1 and 2 GI toxicity, respectively, while 83% had no GI complaint. For GU complaints, 38% and 35% had grade 1 and 2 toxicity, respectively, while 27% had no complaints. There was no grade 3 or higher acute GI or GU toxicity. Mean doses to the bladder were 22.8, 23.4, and 26.1 Gy for grade 0, 1, and 2 GU toxicity, respectively (p = 0.132). There is no statistically significant relationship between acute GU toxicity and the bladder volume receiving > 65 Gy, > 70 Gy, or > 75 Gy. In evaluating acute GI toxicity, there are very few grade 1 and 2 events. No relationship was found between acute rectal toxicity and mean rectal dose or irradiated rectal volumes receiving more than 65, 70, and 75 Gy., Conclusion: The findings are important with regard to the safety of IMRT, especially in reducing acute GI toxicity. Dose escalation with IMRT using a prostate immobilization technique is feasible. The findings are also important because they contribute to the clinical and dosimetric correlation aspect in the use of IMRT to treat prostate cancer. A larger cohort may be needed to determine if there is a relationship between acute GU toxicity and (a) mean bladder dose and (b) irradiated bladder volume receiving > 65 Gy, > 70 Gy, or > 75 Gy. A larger cohort of patients treated to a higher dose may be needed to show a relationship between dose volume and acute GI toxicity.

Acute graft-vs-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem cell transplantation (HSCT), leading to a significant morbidity and mortality. GVHD occurs when transplanted donor T lymphocytes react to foreign host cells. It causes a wide variety of host tissue injuries. This review focuses on the pathobiological basis, clinical aspects, and current management strategies of acute GVHD. Afferent phase of acute GVHD starts with myeloablative conditioning, i.e., before the infusion of the graft. Total-body irradiation (TBI) or high-dose chemotherapy regimens cause extensive damage and activation in host tissues, which release inflammatory cytokines and enhance recipient major histocompatibility complex (MHC) antigens. Recognition of the foreign host antigens by donor T cells and activation, stimulation, and proliferation of T cells is crucial in the afferent phase. Effector phase of acute GVHD results in direct and indirect damage to host cells. The skin, gastrointestinal tract, and liver are major target organs of acute GVHD. Combination drug prophylaxis in GVHD is essential in all patients undergoing allogeneic HSCT. Steroids have remained the standard for the treatment of acute GVHD. Several clinical trials have evaluated monoclonal antibodies or receptor antagonist therapy for steroid-resistant acute GVHD, with different successes in a variety of settings. There are some newer promising agents like mycophenolate mofetil, glutamic acid-lysine-alanine-tyrosine (GLAT), rapamycin, and trimetrexate currently entering in the clinical studies, and other agents are in development. Future experimental and clinical studies on GVHD will shed further light on the better understanding of the disease pathobiology and generate the tools to treat malignant disorders with allogeneic HSCT with specific graft-vs-tumor effects devoid of GVHD.