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A Retrospective Study of Breast Cancer Patients Treated with Quadrantectomy without Radiation Therapy.

BACKGROUND: Radiation therapy after breast-conserving surgery (BCS) reduces the risk of local recurrence. However, whether radiation therapy is necessary forall patients undergoing BCS remains unclear. METHODS: In order to determine the selection criteria for patients who can safely omit radiation therapy and to confirm the survival benefit of quadrantectomy without radiation therapy, we reviewed 107 patients who underwent quadrantectomy without radiation therapy between February 1988 and July 1995. RESULTS: The 5-year overall survival, disease-free survival and cumulative local recurrence rates were 93.7%, 80.7% and 12.1% respectively. There were no significant differences of 5-year overall survival (94.0% vs 94.1%) and disease-free survival rates (83.1% vs 70.0%) between patients with or without tamoxifen. The 5-year cumulative local recurrence rate of patients with tamoxifen, however, tended to be lower (p = 0.0810) than that of patients without tamoxifen. The 5-year cumulative local recurrence rate of the patients aged 45 or less was significantly higher than that of patients aged from 45 to 55 years and those over 55 (p= 0.0090 and 0.0089, respectively). In ER positive patients, the 5-year cumulative local recurrence rate of patients with tamoxifen tended to be lower (p= 0.0791) than that of patients without tamoxifen. CONCLUSION: The survival rate of quadrantectomy without radiation therapy wasacceptable. While the risk of local recurrence following quadrantectomy withoutradiation therapy is substantial, radiation therapy following quadrantectomy might not be necessary in elderly ER positive women receiving adjuvant tamoxifen therapy.

Journal Article↗

The effect of heme oxygenase-1 induction by glutamine on radiation-induced intestinal damage: the effect of heme oxygenase-1 on radiation enteritis.

BACKGROUND: Radiation enteritis is a significant clinical problem in patients receiving ionizing radiation directed at the abdomen or pelvis. The small intestine is the most radiosensitive gastrointestinal organ. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels of the small intestine were measured to determine the oxidative damage caused by radiation. In addition, caspase-3 activity of the small intestine was measured to define the degree of apoptosis. The present study was undertaken to investigate the effect of glutamine administration on heme oxygenase-1 (HO-1) expression of the radiation enteritis model. METHODS: Rats received 1 g/kg/d glutamine (HO-1-inducer) for 7 days before irradiation and continued for 3 days after irradiation. Zn-prothoporphyin (Zn-PP) 40 micromol/kg was delivered subcutaneously for 1 day before irradiation. Intestinal MPO activities and MDA levels are indicators of oxidative damage, whereas caspase-3 activities show the degree of apoptosis of the small intestine. At histopathologic examination, terminal ileum tissue was analyzed for morphologic changes. Also, the nuclear factor-kappa (NF-kappa) expression level of the terminal ileum was determined with immunohistochemistry methods to show the mucosal inflammatory process. RESULTS: Irradiation significantly increased the intestinal MPO and caspase-3 activities, MDA levels, and HO-1 expression in comparison with the sham group. Glutamine treatment was associated with increased HO-1 expression, decreased MPO activity, caspase-3 activity, and MDA levels. Inhibition of HO-1 activity by Zn-PP completely eliminated the protective effects of glutamine. Histopathologic examination showed that the intestinal mucosal structure was preserved in the glutamine-treated group. In the irradiation group, NF-kappaB overexpression was detected. NF-kappaB positivity was strongest in the intestine of animals in the radiation alone group and the Zn-PP-treated irradiation group. CONCLUSIONS: Glutamine appears to have protective effects against radiation-induced intestinal damage. This protective effect is mediated in part by the induction of HO-1 activity because inhibition of Zn-PP resulted in the complete abolishment of the protective effect of glutamine.

Animals↗

Prospective evaluation of formalin therapy for radiation proctitis.

BACKGROUND: Radiation proctitis is a troublesome complication of radiation therapy for as many as 75% of patients after pelvic irradiation. Five percent progress to chronic radiation proctitis complicated by telangiectasias and hemorrhage. The utility of formalin rectal instillation for treatment of bleeding is prospectively evaluated in this study. METHODS: Eleven patients (9 male, 2 female) with rectal bleeding after pelvic irradiation were treated with formalin therapy. In a single treatment, 4% formalin was instilled into the rectum in four separate 20-cc aliquots with total mucosal contact time of approximately 15 minutes. Patients were initially evaluated at 7 to 10 days and 1 month postoperatively and assessed for bleeding. RESULTS: All patients presented with rectal bleeding. Twenty-seven percent required transfusion. Thirty-six percent had failed other previous therapy. In follow-up of 3 to 64 months, 100% had initial success with cessation of bleeding. Three patients had recurrent bleeding; none required transfusion. One patient required repeat formalin instillation, with no further bleeding at 3 months follow-up. CONCLUSION: Local rectal instillation of 4% formalin is an efficacious therapy for treatment of radiation-induced lower gastrointestinal bleeding.

Aged↗

Endoluminal formalin application for haemorrhagic radiation proctitis.

BACKGROUND: Radiation proctitis is a common complication following radiation therapy for pelvic malignancies. This is associated with significant morbidity which adversely affects the quality of life. Local application of formalin has been used effectively in the treatment of radiation proctitis. METHODOLOGY: Thirty patients with haemorrhagic radiation proctitis who underwent endoluminal application of 4% formalin between January 1998 to October 2002 were followed up prospectively to assess the efficacy of the treatment. RESULTS: The follow up ranged from 5 to 36 months (mean 18.1 months). Nineteen (63.3%) patients had complete response to formalin application while 7 (23.3%) patients had partial response. There were 4 (13.3%) failures. No procedure related complication was observed. CONCLUSION: Local application of formalin is a simple, safe, inexpensive and fairly effective outpatient treatment modality for chronic radiation proctitis.

Adult↗

Temporary corneal stem cell dysfunction after radiation therapy.

BACKGROUND: Radiation therapy can cause corneal and conjunctival abnormalities that sometimes require surgical treatment. Corneal stem cell dysfunction is described, which recovered after the cessation of radiation. METHODS: A 44-year-old man developed a corneal epithelial abnormality associated with conjunctival and corneal inflammation following radiation therapy for maxillary cancer. He experienced ocular pain and loss of vision followed by conjunctival epithelialisation of the upper and lower parts of the cornea. RESULTS: Examination of brush cytology samples showed goblet cells in the upper and lower parts of the cornea, which showed increased fluorescein permeability, and intraepithelial lymphocytes. Impression cytology showed goblet cells in the same part of the cornea. Specular microscopy revealed spindle type epithelial cells. Patient follow up included artificial tears and an antibiotic ophthalmic ointment. The corneal abnormalities resolved after 4 months with improved visual acuity without any surgical intervention, but the disappearance of the palisades of Vogt did not recover at 1 year after radiation. CONCLUSION: Radiation therapy in this patient caused temporary stem cell dysfunction which resulted in conjunctivalisation in a part of the cornea. Although limbal stem cell function did not fully recover, this rare case suggested that medical options should be considered before surgery.

Adult↗

Analysis of gene expression using gene sets discriminates cancer patients with and without late radiation toxicity.

BACKGROUND: Radiation is an effective anti-cancer therapy but leads to severe late radiation toxicity in 5%-10% of patients. Assuming that genetic susceptibility impacts this risk, we hypothesized that the cellular response of normal tissue to X-rays could discriminate patients with and without late radiation toxicity. METHODS AND FINDINGS: Prostate carcinoma patients without evidence of cancer 2 y after curative radiotherapy were recruited in the study. Blood samples of 21 patients with severe late complications from radiation and 17 patients without symptoms were collected. Stimulated peripheral lymphocytes were mock-irradiated or irradiated with 2-Gy X-rays. The 24-h radiation response was analyzed by gene expression profiling and used for classification. Classification was performed either on the expression of separate genes or, to augment the classification power, on gene sets consisting of genes grouped together based on function or cellular colocalization.X-ray irradiation altered the expression of radio-responsive genes in both groups. This response was variable across individuals, and the expression of the most significant radio-responsive genes was unlinked to radiation toxicity. The classifier based on the radiation response of separate genes correctly classified 63% of the patients. The classifier based on affected gene sets improved correct classification to 86%, although on the individual level only 21/38 (55%) patients were classified with high certainty. The majority of the discriminative genes and gene sets belonged to the ubiquitin, apoptosis, and stress signaling networks. The apoptotic response appeared more pronounced in patients that did not develop toxicity. In an independent set of 12 patients, the toxicity status of eight was predicted correctly by the gene set classifier. CONCLUSIONS: Gene expression profiling succeeded to some extent in discriminating groups of patients with and without severe late radiotherapy toxicity. Moreover, the discriminative power was enhanced by assessment of functionally or structurally related gene sets. While prediction of individual response requires improvement, this study is a step forward in predicting susceptibility to late radiation toxicity.

Aged↗

Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis.

BACKGROUND: Radiation proctitis is a common complication of abdominal and pelvic radiotherapy; unfortunately, there is no established effective therapy for radiation proctitis. Short-chain fatty acids (SCFA) have been effectively used to treat a variety of colitides. We sought to determine whether SCFA enemas have a role in the treatment of radiation proctitis. METHODS: Seven patients completed an open-labeled, pilot study to evaluate the effect of SCFA on clinical, endoscopic, and pathological parameters of radiation proctitis. RESULTS: Four weeks of treatment with SCFA enemas resulted in clinical improvement in all patients. There were modest, but not significant, changes in endoscopic and pathological parameters. CONCLUSION: SCFA are a promising therapeutic option in radiation proctitis.

Adult↗

Epidermal growth factor enhances intestinal mitotic activity and DNA content after acute abdominal radiation.

BACKGROUND: Mediators of radiation-induced enteritis and colitis remain undefined. Epidermal growth factor (EGF) is an endogenous peptide that is trophic to the gastrointestinal tract. We tested the hypothesis that EGF enhances DNA synthesis and mitotic activity and prevents acute radiation enteritis after total abdominal radiation. METHODS: Four equal groups (n = 6) of Sprague-Dawley rats were studied: I (control), II (radiation), III (EGF), and IV (radiation + EGF). Animals in groups III and IV received EGF (10 micrograms/kg) every 8 hours for 48 hours before radiation exposure and for 72 hours after radiation, and the remaining animals were given an equal volume of vehicle. Animals in groups II and IV were administered a single dose of abdominal radiation (1000 cGy) 48 hours after the start of either vehicle or EGF. Distal ileum and colon were harvested 72 hours after radiation, examined histologically, and assayed for total DNA content. RESULTS: Group II or radiated animals had diarrhea, significant weight loss (p < 0.05), and decreased food consumption consistent with acute clinical radiation enteritis. Mitotic activity and total DNA content were significantly reduced (p < 0.05) when compared with group I (nonradiated controls). Group IV animals treated with EGF and exposed to radiation did not suffer the acute clinical manifestations of radiation enteritis. In addition, total DNA content and mitotic activity of the terminal ileum increased significantly (p < 0.05), and a significant increase in mitotic activity occurred in the distal colon when compared with radiated controls. CONCLUSIONS: The results of this study suggest that (1) a decrease in mitotic activity and total DNA content occurs early and persists for at least 72 hours after acute radiation, (2) EGF treatment significantly increases small and large bowel mitogenicity in acutely radiated animals, and (3) EGF significantly decrease the acute clinical manifestations of radiation enteritis.

Abdomen↗

Environmental radiation as the conditioning factor for the survival of yeast Saccharomyces cerevisiae.

Whether natural radiation can be a conditioning factor for the growth and survival of a living organism was investigated using diploid yeast S. cerevisiae D7. Yeast cells were conditioned by growing them continuously for at least 100 generation in 3 different radiation background such as i) ambient radiation (1.1 mSv/y), ii) sub-ambient radiation (0.44 mSv/y, within a shielded chamber) and iii) an elevated background radiation (88 and 880 mSv/y in a gamma-field). At the end, the cells were challenged with 60Co gamma, 100 Gy and the viable fractions were determined. Conditioning the cells in 880 mSv/y and in ambient radiation, enabled the cells to reduce the deleterious effect of the challenging dose significantly (P < 0.05) compared to that of sub-ambient radiation. The cellular viability of yeast cultures seems to be influenced by the prevailing radiation background, apart from starvation. Comparatively, a rapid decline in viability was noticed when the cultures were incubated for 60 days in the shielded chamber. The results indicate that some amount of radiation equivalent to background level or little above is needed to confer fitness in biological systems against stress factors, including radiation. The adaptive dose for the diploid yeast was also determined by single exposure. The priming dose ranged from 0.01 to 1.2 Gy. An adaptive dose of 0.25 or 0.4 Gy, almost nullified the deleterious effect of the challenging dose. The adaptive response may have a greater role in the field of cancer therapy and in radiation risk assessment. Understanding the response of an organism at different radiation-background will be helpful for successful space management.

Adaptation, Physiological↗

Altitude, radiation, and mortality from cancer and heart disease.

The variation in background radiation levels is an important source of information for estimating human risks associated with low-level exposure to ionizing radiation. Several studies conducted in the United States, correlating mortality rates for cancer with estimated background radiation levels, found an unexpected inverse relationship. Such results have been interpreted as suggesting that low levels of ionizing radiation may actually confer some benefit. An environmental factor strongly correlated with background radiation is altitude. Since there are important physiological adaptations associated with breathing thinner air, such changes may themselves influence risk. We therefore fit models that simultaneously incorporated altitude and background radiation as predictors of mortality. The negative correlations with background radiation seen for mortality from arteriosclerotic heart disease and cancers of the lung, the intestine, and the breast disappeared or became positive once altitude was included in the models. By contrast, the significant negative correlations with altitude persisted with adjustment for radiation. Interpretation of these results is problematic, but recent evidence implicating reactive forms of oxygen in carcinogenesis and atherosclerosis may be relevant. We conclude that the cancer correlational studies carried out in the United States using vital statistics data do not in themselves demonstrate a lack of carcinogenic effect of low radiation levels, and that reduced oxygen pressure of inspired air may be protective against certain causes of death.

Altitude↗

[Knowledge and attitudes of Mexican population concerning solar radiation].

BACKGROUND: The effects of solar radiation in human health is dependent upon environment, behavior, and genetic characteristics. OBJECTIVE: Identify phenotypic features, attitudes, knowledge and preventive measures concerning sun exposure among a local population. METHODS: People older than 15 years were interviewed concerning time of sun exposure, photoprotection, and general knowledge about adverse effects of sun irradiation. RESULTS: 964 questionnaires were analyzed. White-skin population represented 7.4%, light-brown 24.8%, dark-brown 67.8%. Exposure time on working days was up to 15 min in 27.8%, and more than 60 min in 38.8%. On weekends, time exposure was similar. 30% did not take any preventive measures 41% wore hats and 11.8% used sunscreens. Among participants, 85.4% were aware that sun exposure caused skin cancer, 64. 1% knew that mortality is increased, 83.4% reported that excessive sun exposure is related to aging of the skin, and 26.5% believed tanning is healthy. CONCLUSIONS: In spite of thefact that a great majority of the population recognized that sun exposure produces aging and skin cancer, their exposure is widespread. This survey may be a valuable tool to design preventive public health campaigns that target high risk groups.

Adolescent↗

Background ionizing radiation plays a minor role in the production of chromosome translocations in a control population.

PURPOSE: To obtain a relationship between background chromosome translocation frequency and age with translocation frequency measured to a high statistical precision, and to identify the role of background ionizing radiation in the production of chromosome translocations in a control population. MATERIALS AND METHODS: Lymphocytes from 35 healthy control individuals (15 females and 20 males) were scored, using fluorescence in situ hybridization, for the presence of chromosomal translocations. Translocation frequencies were measured to a high statistical precision (s.d. 25% or less for each individual). These control subjects were of varying ages, ranging from 0 (cord blood) to 98 years. RESULTS: In a total of 521,492 metaphases (203,754 genome equivalent cells) scored, an average of 5,822 genome equivalent cells per individual, 764 translocations were observed in the 35 individuals. The translocation frequencies ranged from 0 (for cord blood) to 0.0167 (for a 98 year old) translocations per cell. The average age and translocation frequency was 50 years and 0.004 translocations per cell, respectively. The best fit of the relationship between translocations and age was: Y=7x10(-4)+6.9x10(-6)A+1.35x10(-6)A2, which does not obey the linear relationship expected from chronic background radiation alone. The curvilinear relationship observed clearly shows that other endogenous and exogenous clastogens or clastogenic events, in addition to radiation, serve to generate chromosome translocations in control populations. CONCLUSION: The background translocation frequency in control individuals follows a curvilinear relationship with age. No significant variation was observed between individuals of the same age. Clastogenic processes of normal aging and physiological factors in additional to ionizing radiation play a major role in the production of chromosome translocations in a control population. Background radiation, however, appears to play a minor role in chromosome translocation production in control individuals living near sea level.

Adult↗

Perception of radiation hazards.

The health risks of radiation have been carefully studied and are relatively well understood in comparison with other risks to the human environment. Public perception of these risks often is distorted, due in part to lack of familiarity with the actual risk levels involved. There is a need for dissemination to the public of accurate information on radiation risks as well as to patients and volunteer subjects for studies involving radiation exposures. Often such information can be presented meaningfully by comparing the risks of radiation exposure with other, more familiar risks. Natural background radiation is a universally present and generally accepted source of risk, and thus serves as one reference against which to compare the risks of other radiation exposures. Natural background radiation averages about 100 mrem/yr, but much higher levels are encountered in some parts of the US (400 mrem/yr) and worldwide (2,000 mrem/yr). These variations are due primarily to differences in cosmic ray intensity with altitude and in terrestrial radiation originating from soil and rocks. Radiation risks also may be compared with the risks of other human activities, both voluntary and involuntary. The former are useful for comparisons with the risks of voluntary radiation exposures such as occupational exposure and participation in medical or research procedures involving radiation. Involuntary radiation exposure, such as might result from the transportation and disposal of radioactive waste, poses a more complicated issue. Comparisons of such exposures to natural background radiation levels and their variations are helpful. Two other concepts that have been proposed for assessing the relative risk of low-level radiation exposure are "de minimus risk" and "probability of causation." The former suggests that there is some minimal level of involuntary risk that can be considered acceptable, provided it carries with it some benefit to society or the individual. The latter is a concept that has been introduced in legislation to decide compensation for alleged injuries from radiation exposures.

Abnormalities, Radiation-Induced↗

The 1999 Lauriston S. Taylor lecture--back to background: natural radiation and radioactivity exposed.

I am profoundly grateful for being chosen as the twenty-third presenter of the Lauriston S. Taylor Lecture, and I share this honor with a list of distinguished scientists, including my husband, who pay tribute to the premier leader in radiation protection. In 1938, Laurie was working for the National Bureau of Standards and chaired the Advisory Committee on X-ray and Radium Protection, a group of 8 persons, who set the pace for all forthcoming radiation standards. NBS had, since 1913, been standardizing essentially all of the radium offered for sale in the U.S., and the problem arose to revise the handbook on proper conditions for handling radium based on the then current knowledge. This resulted in Handbook 23 (1938) superseding the 1934 work. At the time Laurie was a scientist working in the measurements side of radiation and though he contributed much to that field, his name is inseparably linked with guidance in radiation protection. Today we pay tribute for his leadership that he carried out with intelligence, grace, and personal warmth. My talk today deals mostly with measured data for naturally occurring internal radiation emitters and how these data can be used for predictive purposes in estimating the dose and risk from internal body contamination. This stresses the "and Measurements" part of the Council's title. The topic of this year's NCRP Annual Meeting is "Radiation Protection in Medicine: Contemporary Issues." I believe that physicians and State and Federal agencies will have to cope with complaints following various exposure situations resulting from the cleanup of background radionuclides during closure at nuclear facilities, military use of radioactivity, and occurrences of high natural background in some locations. They will find comfort in the knowledge that existing background radiation data can be the basis for predictions of realistic dose and risk in most situations.

Background Radiation↗

Is natural background or radiation from nuclear power plants leukemogenic?

In view of the enormous number of base pair replications per annum in hemopoietic stem cells with the likelihood of coding errors, the rarity of the leukemogenic event at the cellular level after high doses of radiation, the infrequent occurrence of radiation events in cells at low-level exposure (large fraction of cells uninvolved), biological protective mechanisms and the realization that exposure of human populations to radiation from nuclear power plants is a very small fraction of natural radioactivity and will for the foreseeable future remain small and that populations exposed to high natural background radiation show no detectable harmful effects, it is concluded that either there is no effect, or for statistical reasons one cannot detect an effect.

Adult↗

Quantitative and qualitative changes of the seminiferous epithelium induced by Ga. Al. As. (830 nm) laser radiation.

BACKGROUND AND OBJECTIVES: Low level laser radiation stimulates both nucleic acid synthesis and cellular proliferation in E. coli, Hela tumor cells, fibroblasts, lymphocytes, and thyroid cells. It has been introduced as a therapeutic modality; nevertheless few studies have been carried out to determine the effects of laser radiation on the testes or spermatogenesis. The aim of this study was to determine the quantitative and qualitative changes of the seminiferous epithelium after Ga. Al. As. (830 nm) laser radiation. STUDY DESIGN/MATERIALS AND METHODS: The left testes of Sprague-Dawley rats were daily exposed to laser light for 15 days; so the cumulative doses used 28.05 and 46.80 J/cm(2) in two experimental groups. Sampling carried out 24 hours after the last treatment and samples were processed for LM and TEM study. RESULTS: The number of germ cells specially the pachytene spermatocytes and elongated spermatids increased after 28.05 J/cm(2) laser radiation. Ultrastructural features of germ and Sertoli cells in this group were similar to that of control; while laser irradiation at 46.80 J/cm(2) had a destructive effect on the seminiferous epithelium such as dissociation of immature spermatids and evident ultrastructural changes in them. CONCLUSIONS: The findings confirmed the existence of a biostimulatory threshold of applied laser energy and the importance of determining it for clinical applications. Moreover, it was revealed that low doses of laser light have a biostimulatory effect on the spermatogenesis and may provide benefits to the patients with oligospermia and azoospermia.

Animals↗

Neurological effects of radiofrequency radiation.

BACKGROUND: The health effects of radiofrequency radiation (RFR) and the adequacy of the safety standards are a subject of debate. One source of human data is case reports regarding peripheral neurological effects of RFR, mainly noxious sensations or dysaesthesiae. AIM: To investigate health effects, neurophysiological mechanisms and safety levels for RFR. METHODS: We conducted a literature search for case reports and case series associated with mobile phone technology as well as other RFR sources using specific search terms on PubMed. RESULTS: We identified 11 original articles detailing case reports or case series and matching the search criteria. Five of the identified papers were written by at least one of the authors (B.H. or R.W.). CONCLUSIONS: Cases have arisen after exposure to much of the radiofrequency range. In some cases, symptoms are transitory but lasting in others. After very high exposures, nerves may be grossly injured. After lower exposures, which may result in dysaesthesia, ordinary nerve conduction studies find no abnormality but current perception threshold studies have found abnormalities. Only a small proportion of similarly exposed people develop symptoms. The role of modulations needs clarification. Some of these observations are not consistent with the prevailing hypothesis that all health effects of RFR arise from thermal mechanisms.

Cell Phone↗