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Background: The effective dose to circulating immune cells (EDIC) is associated with survival in lung and esophageal cancer patients. This study aimed to evaluate the benefit of intensity-modulated proton therapy (IMPT) for EDIC reduction as compared to volumetric modulated arc therapy (VMAT) in patients with locally advanced breast cancer (BC). Materials and methods: Ten BC patients treated with locoregional VMAT after breast-conserving surgery were included. Mean dose to the heart (MHD), lungs (MLD), and liver (MlD), as well as the integral dose to the body (ITD), were retrieved, and we calculated EDIC as 0.12 × MLD + 0.08 × MHD + 0.15 × 0.85 × √(n/45) × MlD + (0.45 + 0.35 × 0.85 × √(n/45)) × ITD/(62 × 103), where n is the number of fractions. EDIC was compared between VMAT and IMPT plans. Results: Median EDIC was reduced from 3.37 Gy (range: 2.53–5.99) with VMAT to 2.13 Gy (1.31–3.77) with IMPT (p < 0.01). For left-sided BC patients, EDIC was reduced from 3.15 Gy (2.53–3.78) with VMAT to 1.65 Gy (1.31–3.77) with IMPT (p < 0.01). For right-sided BC patients, EDIC was reduced from 5.60 Gy (5.06–5.99) with VMAT to 3.38 Gy (3.10–3.77) with IMPT (p < 0.01). Right-sided BC patients had a higher EDIC irrespective of the technique. Integral dose reduction was the main driver of EDIC reduction with IMPT and was associated with lung sparing for left-sided BC patients or liver sparing for right-sided BC patients. Conclusion: IMPT significantly reduced EDIC in BC patients undergoing locoregional adjuvant radiotherapy. Integral total dose reduction, associated with improved lung sparing in left-sided BC patients or liver sparing in right-sided BC patients, mainly drove EDIC reduction with IMPT. The emergence of dynamic models taking into account the circulatory kinetics of immune cells may improve the accuracy of the estimate of the dose received by the immune system compared to calculation of the EDIC, which is based solely on static dosimetric data. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer with peritoneal metastases can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Treatment may result in biopsychosocial late effects (LEs). We explored the frequency and severity of the following biopsychosocial LEs: anxiety, depression, fear of cancer recurrence (FCR), insomnia, fatigue, cognitive impairment, and pain, and evaluated their impact on quality of life (QoL). Method: This was a national prospective cohort study screening for LEs during the period January 2021–May 2023. Patients completed the following questionnaires: General Anxiety Disorder-7, Patient Health Questionnaire-9, FCR Inventory-Short Form, Insomnia Severity Index, Functional Assessment of Chronic Illness Therapy-Fatigue, cognitive impairment (six items from the European Organisation for Research and Treatment of Cancer Item Library), and the Rectal Cancer Pain Score. Preregistration was completed at ClinicalTrials.gov (NCT04956107). Result: In total, 99 patients were included. The mean age was 61 years and 57% were women. At 3 months after surgery, the frequent LEs were fatigue (72%), FCR (58%), and pain (48%), and at 12 months after surgery, the frequent LEs were FCR (65%), fatigue (40%), and insomnia (33%). More than half of the patients (54%) reported at least two LEs after 12 months. Patients with moderate-to-severe LEs reported a lower QoL than patients with no/mild LEs. Patients with no/mild LEs had a similar QoL as the Danish norm population. Conclusion: Biopsychosocial LEs were prevalent. The QoL of patients reporting LEs in the worst severity categories was negatively impacted. Screening and treatment for these LEs should be a focus in cancer survivor follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Because the population of older gastric cancer survivors (GCSs) is growing, understanding the long-term late effects experienced by these GCSs and their impact on survival outcomes is crucial for optimizing survivorship care. This study aims to identify and characterize these effects and investigate their association with survival outcomes. Methods: A retrospective analysis of electronic health records was conducted on 9,539 GCSs diagnosed between 2011 and 2017. The GCSs were divided into two age groups (< 65 and ≥ 65 years) and the long-term late effects were categorized by age using Cox proportional hazard models. The impact of clinical factors and age-specific late effects on survival was evaluated in the older GCSs. Results: Among the total GCSs, 37.6% were over and 62.4% were under 65 years of age. Significant differences between the age groups were observed in the cumulative hazard ratios (HRs) for iron and vitamin B12 levels and prognostic nutritional index (PNI) scores. In older GCSs, abnormal iron levels (HR 1.98, 95% CI 1.16–3.41, p =.013) and poor PNI scores (HR 1.59, 95% CI 1.03–2.47, p =.038) were associated with poorer survival outcomes. Additionally, being female was identified as a risk factor for lower survival rates (if male, HR 0.42, 95% CI 0.18–0.98, p =.045). Conclusion: This study highlights the typical long-term late effects experienced by older GCSs. By tailoring survivorship care to address nutritional-, age-, and gender-related factors, the overall survival and quality of life of older GCSs can be improved. [ABSTRACT FROM AUTHOR]

The management of brain tumors developed in adolescents and young adults (AYAs) is challenging because of their histological heterogeneity and low incidence. The brain tumor and its treatment interventions can negatively affect neurological, neurocognitive, and endocrinological function, and dramatically affect the circumstances of AYA patients progressing to further education, employment, and marriage. Specific support is thus necessary to maintain the quality of life (QOL) of AYA brain tumor patients. AYA patients and survivors require active intervention and support for returning to school or work, progressing to further education, finding employment, and preserving fertility. Recent cancer genome profiling revealed that AYA gliomas include pediatric- and adult-type genetic alteration. Insights into the biology underlying the distribution of tumors in AYAs may influence the development of prospective trials. A more individualized view of brain tumors may influence stratification of patients' in future clinical studies as well as selection for molecular targeted therapy. Here I review strategies for achieving a better outcome to decrease late effects and improve QOL. [ABSTRACT FROM AUTHOR]

Aims: Sexual abuse is a women's health concern globally. Although experience of sexual abuse and cancer may constitute risk factors for sexual dysfunction and low wellbeing, the effects of sexual abuse have received little attention in oncology care. This study aims to explore sexual health and wellbeing in women after pelvic radiotherapy and to determine the relationship between sexual abuse and sexual dysfunction, and decreased wellbeing. Methods: Using a study-specific questionnaire, data were collected during 2011–2017 from women with gynaecological, anal, or rectal cancer treated with curative pelvic radiotherapy in a population-based cohort and a referred patient group. Subgroup analyses of data from women with a reported history of sexual abuse were conducted, comparing socio-demographics, diagnosis, aspects of sexual health and wellbeing. Results: In the total sample of 570 women, 11% reported a history of sexual abuse and among these women the most common diagnosis was cervical cancer. More women with than without a history of sexual abuse reported feeling depressed (19.4% vs. 9%, p = 0.007) or anxious (22.6% vs. 11.8%, p = 0.007) and suffering genital pain during sexual activity (52% vs. 25.1%, p = 0.011, RR 2.07, CI 1.24–3.16). In the total study cohort, genital pain during sexual activity was associated with vaginal shortness (68.5% vs. 31.4% p ≤ 0.001) and inelasticity (66.6% vs. 33.3%, p ≤ 0.001). Conclusions: Our findings suggest that a history of both sexual abuse and pelvic radiotherapy in women are associated with increased psychological distress and sexual impairment, challenging healthcare professionals to take action to prevent retraumatisation and provide appropriate interventions and support. [ABSTRACT FROM AUTHOR]

BACKGROUND: Skin is the body's fi rst defence against direct exposure to variety of chemicals. Polycyclic aromatic hydrocarbons such as 3-methylcholanthrene (3-MC) are common in polluted urban air and have a potential of producing harmful effects. Moreover, their late effects can occur months or years after exposure. OBJECTIVES: We aimed to investigate the long-term effects of 3-MC induced dermal toxicity on the expression of markers of apoptosis, pleiotropic cytokines, and oxidative stress and to determine the protective effect of cisplatin. METHODS: Groups were designed as control (group 1), 3-MC applied (group 2) and 3-MC+cisplatin applied mice (group 3). Cutaneous expressions of TGFß, PDGFA, PDGFC, bFGF, PDGFRa, USP28, and Ki67 were evaluated with qPCR. Total oxidant (TOS), total antioxidant (TAS) and oxidative stress index (OSI) values were determined in liver and kidney tissues. RESULTS: The expression levels of TGFß, PDGFRa, USP-28, Ki67, and PDGFA were decreased significantly in MC applied groups. Renal TAS levels were significantly lower in group-3. Liver and kidney OSI values were increased in both groups 2 and 3. CONCLUSION: The results indicated that low dose 3-MC caused oxidative stress and downregulated apoptotic and cytokine markers in the long term and cisplatin had no ameliorative effects on this degeneration processes (Tab. 3, Fig. 3, Ref. 32). Text in PDF www.elis.sk. [ABSTRACT FROM AUTHOR]

Purpose: Cancer treatment-related late effects degrade survivors' quality of life, independence, and societal integration, yet may be ameliorated, or even reversed, with effective care. Unfortunately, survivors inconsistently receive this care and the impact on their healthcare utilization is unknown. We sought to estimate differences in utilization between breast cancer (BC) survivors with and without upper extremity lymphedema; a common, remediable late effect.Methods: We conducted a population-based, retrospective longitudinal cohort study of survivors with incident BC diagnosed from January 1, 1990, through December 31, 2010. HC utilization was characterized using the Berenson-Eggers Type of Service (BETOS) categories. Outcomes included overall healthcare utilization as well as its compartmentalization into the BETOS categories of (1) Evaluation and management, (2) Procedures, (3) Imaging, (4) Tests, (5) Durable medical equipment, (6) Physical/occupational therapy, (7) Other, and (8) Exceptions/Unclassified.Results: The cohort included 1906 subjects of which 94% (1800) had records meeting the inclusion criteria. Mean follow-up per survivor was 12.8 years (mean, 11, range 1-25 years). Analysis revealed that (1) survivors with BC-associated lymphedema used > 30% more services annually; (2) their increased utilization lessened but persisted for at least 10 years after diagnosis; and (3) this finding of increased utilization extends across all BETOS categories, is further amplified as BMI increases, and cannot be explained solely by lymphedema-directed care.Conclusions: BC-related lymphedema appears to be an important driver of survivors' healthcare utilization and guideline-concordant activities to reduce its incidence and severity may be cost neutral or saving.Implications For Cancer Survivors: Early detection and effective management of cancer-related late effects like lymphedema may reduce survivors' healthcare needs in the decades that follow their cancer treatment. [ABSTRACT FROM AUTHOR]

The effects of developmental exposure to 3,3′ -iminodipropionitrile (IDPN), a neurotoxicant that causes proximal axonopathy, on mouse hippocampal neurogenesis was examined. Pregnant mice were exposed to IDPN at 0, 600, or 1200 ppm in their drinking water from gestational day 6 to postnatal day (PND) 21. On PND 21, male offspring showed increased postmitotic neuron-specific NeuN-immunoreactive granule cell numbers in the dentate subgranular zone (SGZ) and granule cell layer (GCL) and decreased glutamate receptor gene Grin2d levels in the dentate gyrus at 1200 ppm. On PND 77, decreased numbers were observed for TBR2 progenitor cells in the SGZ at ≥600 ppm and GFAP stem cells, DCX progenitor cells and immature granule cells, NeuN immature and mature granule cells, PCNA proliferating cells in the SGZ and/or GCL, and immunoreactive cells for ARC or FOS, immediate-early gene products related to neuronal and synaptic plasticity, in the GCL at 1200 ppm. Additionally, at 1200 ppm of IDPN, downregulation of Kit, the gene encoding the stem cell factor (SCF) receptor, and upregulation of Kitl, encoding SCF, were observed in the dentate gyrus. Therefore, maternal IDPN exposure in mice affects neurogenesis involving glutamatergic signals at the end of developmental exposure, with late effects suppressing SGZ cell proliferation, reducing the broad range of granule cell lineage population, which may be responsible for SCF receptor downregulation. The upregulated SCF was likely a feedback response to the decreased receptor level. These results suggest that reduced SCF signaling may cause suppressed neuronal and synaptic plasticity. [ABSTRACT FROM AUTHOR]

Purpose: This study seeks to assess the differences in disease and socioeconomic characteristics, late effects and long-term quality of life (QoL) after head-and-neck cancer (HNC) among participants and non-participants.Methods: Five hundred sixty recurrence-free survivors treated for HNC at least 6 months previously were invited to participate in a repeated measure, controlled intervention study of computerized Patient Reported Outcome (PRO), which is provided to treating physicians at the point of care. Two hundred sixty-six consented to participate, and 292 declined; of those who declined, 103 filled in the baseline questionnaire. Late effects and QoL were evaluated on the EORTC QLQ C-30 and EORTC QLQ H&N35 and HADS questionnaires, and an empirically derived symptom list was prepared with hospital clinicians.Results: Participants were younger, had a higher educational level, were more likely to cohabit, less likely to smoke, used less alcohol and were more likely to have HPV than those who declined but did not differ by gender, cancer site, stage or time since diagnosis. Participants reported significantly better QoL and functioning and less severe symptoms than those who declined participation other than filling in the baseline questionnaire.Conclusions: Late symptoms are common in HNC survivors. A wide diversity of self-reported late effects was found in this trial with participants significantly less affected than non-participants.Implications For Cancer Survivors: Generalizable data on non-participation may aid in the interpretation of studies on HNC survivors in general and may have relevance for targeting recruitment and maintenance in rehabilitation and follow-up care, outside clinical trials. [ABSTRACT FROM AUTHOR]

Although substantial increases in survival rates among children diagnosed with cancer have been observed in recent decades, survivors are at risk of developing therapy-related chronic health conditions. Among children and adolescents treated for cancer, acquisition of peak bone mass may be compromised by cancer therapies, nutritional deficiencies, and reduced physical activity. Accordingly, failure to accrue optimal bone mass during childhood may place survivors at increased risk for deficits in bone density and fracture in later life. Current recommendations for the treatment of bone density decrements among cancer survivors include dietary counseling and supplementation to ensure adequate calcium and vitamin D intake. Few strategies exist to prevent or treat bone loss. Moving forward, studies characterizing the trajectory of changes in bone density over time will facilitate the development of interventions and novel therapies aimed at minimizing bone loss among survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to assess the late oral complications and the role of salivary gland hypofunction in the severity of mucosal reaction in nonsurgical head and neck cancer patients, submitted to radiotherapy with or without chemotherapy. Methods and materials: Five hundred fifteen charts from patients treated between 2005 and 2009 were reviewed, and 41 patients met the inclusion criteria. Salivary gland function was assessed using a simplified grading system (GSX) and sialometry. Late effects were assessed using the Common Toxicity Criteria (CTC Version 2.0). Results: The average follow-up was 17.1 (4-51) months. A statistical correlation was found for whole salivary flow rates and the average CTC grades for the mucous membrane. Both unstimulated/stimulated whole salivary flow rates (<0.09 mL/min) were identified as potential risk factors ( p < 0.05) and an independent predictor for late mucous membrane toxicity (≥grade 2). A significant correlation was also found between unstimulated salivary flow rates-GSX scores ( p = 0.001) and CTC grades for salivary glands. Eighty-five percent of the patients were classified as suffering from salivary gland hypofunction, as well as 58.2 % considered dryness of the mouth the most debilitating complication. Conclusions: Considering the late effects assessed, the salivary gland hypofunction was the most significant and received the highest morbidity graduation (grade 2/grade 3); xerostomia was also considered the most debilitating complication after treatment. Data show the role of salivary gland hypofunction in the severity of late mucous membrane complication. [ABSTRACT FROM AUTHOR]

Purpose: Currently, no instruments are available to assess symptoms secondary to lymphedema in patients with head and neck cancer (HNC). The study aim was to develop and conduct preliminary tests of such an instrument. Methods: A preliminary item pool was generated from a literature review, previous work in breast cancer-related lymphedema, and an observational study. The item pool was revised based on an expert panel's suggestions and feedback from 18 patients with HNC. The current questionnaire, the Lymphedema Symptom Intensity and Distress Survey-Head and Neck (LSIDS-H&N), was then pilot tested in 30 patients with HNC. Results: Preliminary testing (1) demonstrated feasibility, readability, and ease of use of the LSIDS-H&N and (2) identified that there was a considerable level of symptom burden in the cohort of patients in the piloting sample. Conclusion: Content validity of the LSIDS-H&N was supported by the expert panel during development of the LSIDS-H&N. Further testing is ongoing. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have assessed physical and psychological status in long-term survivors of childhood solid tumors in Japan. For children with such diseases diagnosed and treated in our hospital, our purpose was to clarify the physical and psychological status of long-term survivors and their parents.Methods: Subjects were 56 patients who were diagnosed at our institution as having a childhood malignant solid tumor between 1982 and 2005 and had been alive for at least 5 years after treatment. Surveys were sent and returned by mail.Results: Of the 56 patients surveyed, 32 responded. The current health condition and psychosocial status of survivors were evaluated as good by their parents. However, psychological tests revealed psychosocial problems in 28.1% of the children. Severe posttraumatic stress associated with the child's disease and its treatment was present in 15.6% of the parents.Conclusion: Physical status of long-term survivors of childhood malignant solid tumors was good in general. However, psychological tests revealed psychosocial problems in some of the children and posttraumatic stress in the parents. Considering the diversity of both the diseases and their clinical course, a qualitative study is warranted for further analysis. [ABSTRACT FROM AUTHOR]

Introduction: There is a lack of data on physical activity (PA) and fitness of adolescent and young adult very long-term survivors of childhood acute lymphoblastic leukemia (ALL). Methods: We studied 21 childhood ALL long-term survivors (aged 16-30 years, median time since diagnosis 15.9y), diagnosed in 1986-1996, with age- and sex-matched controls. Peak oxygen uptake (VO) and muscle strength were measured and physical activity index (PAI; MET h/week) calculated. Results: Mean VO of the ALL survivors was 34.8 ± 9.3 ml/kg/min. This was 14% lower than that of the controls (−5.7 ml/kg/min, 95% CI −9.4 to −1.9, p = 0.01), and all the 11 female survivors performed below the age-adjusted reference values. The survivors also performed poorer in the sit-up and maximal jump tests ( p = 0.02 and p = 0.004). Body mass index and PAI were similar in survivors and controls ( p = 0.34 and p = 0.52). Nonetheless, as much as 30% of the male survivors and 36% of the female survivors had PAI ≤ 5 indicating very low levels of physical activity (PA). Conclusions: Insufficient PA and poor physical fitness are clinically important issues in childhood ALL long-term survivors treated with modern protocols. Girls seem to be especially at risk. PA and better physical fitness decrease cardiovascular mortality irrespective of weight. Thus, PA should be promoted throughout and after the treatment for ALL. Implications for cancer survivors: Since insufficient PA and poor physical fitness are an issue in very long-term ALL survivors, they should be informed on the benefits of physical activity, and be strongly encouraged to adopt a physically active lifestyle. [ABSTRACT FROM AUTHOR]

We present a set of tests for physical performance used for annual prospective follow-up after a pediatric transplant. Of the 103 eligible patients transplanted at a mean age of 8.8 years, 94 were included. The results were divided into early, performed 1 (n=46) or 2 (n=12) years post transplant, and late tests (n=66), performed 4–16 (mean 6) years post transplant. A total of 30 patients had tests both at early and late time points (paired tests). The control subjects included 522 healthy age- and gender-matched schoolchildren. Using their test results, the s.d. score (SDS) was calculated for each patient and for each test individually. Both in the early and late tests, patients had the mean SDS for each test significantly lower (P<0.001) than controls, varying from −0.6 to −2.0 SDS. Specifically, tests measuring trunk muscles gave impaired results. In the group with paired tests, the results improved in four of six tests. In late tests, age at SCT, extensive chronic GVHD and being a sports club member correlated with the results. The potential beneficial effect of an exercise intervention program on impaired physical performance after pediatric SCT merits prospective studies. [ABSTRACT FROM AUTHOR]

This study estimated the risk of second primary malignancies after Hodgkin's lymphoma (HL) in relation to family history of cancer, age at diagnosis and latency, among 6946 patients treated for HL in Sweden in 1965-1995 identified through the Swedish Cancer Register (SCR). First-degree relatives (FDRs) to the HL patients and their malignancies were then ascertained together with their malignancies through the Multi-Generation Registry and SCR. The HL patient cohort was stratified on the number of FDRs with cancer, and standardised incidence ratios (SIRs) of developing SM were analysed. In the HL cohort, 781 SM were observed 1 year or longer after HL diagnosis. The risk for developing SM increased with the number of FDRs with cancer, SIRs being 2.26, 3.01, and 3.45 with 0, 1, or >or=2 FDRs with cancer, respectively. Hodgkin's lymphoma long-term survivors treated at a young age with a family history of cancer carry an increased risk for developing SM and may represent a subgroup where standardised screening for the most common cancer sites could be offered in a stringent surveillance programme. [ABSTRACT FROM AUTHOR]

We compared late side effects and quality of life (QoL) in 430 survivors of childhood acute leukaemia based on whether they had undergone haematopoietic cell transplantation (n=142) or not (n=288). Mean age was 18.2 years and mean follow-up duration was 11.9 years. Multivariate logistic regression analyses were performed to compare the risk of each type of late effect in the two groups. Based on age, VSP-A or SF36 questionnaires were used to assess QoL. For each QoL dimension, multiple linear regression was done to construct models of association with the treatment group. Transplanted patients experienced more side effects, including height growth failure, gonadal dysfunction, hypothyroidism and cataract. Children and adolescents in the two treatment groups reported similar QoL levels for almost all dimensions except a better perception of school work by young transplanted children and more difficulties in relating to the medical staff for transplanted adolescents. In adults, two differences in physical domain of QoL were detected but the calculated effect sizes were less than 0.2 in each case, suggesting an uncertain clinical significance. In spite of a higher risk of physical adverse events in the transplanted group, very few clinically significant differences in QoL are detectable.Bone Marrow Transplantation (2007) 40, 897–904; doi:10.1038/sj.bmt.1705821; published online 20 August 2007 [ABSTRACT FROM AUTHOR]

Summary:Between September 1986 and June 1997, 24 children with high-risk ALL in CR1 were allografted after TAM (fractionated TBI, high-dose Ara-C, and melphalan; n=10) or BAM protocol (busulfan, high-dose Ara-C, and melphalan; n=14). The EFS for transplants from sibling donors was 33%with TAM and 62%with BAM (P=0.148). The probability of acute GvHD was 70%with TAM and 15%with BAM (P=0.003). Four of 17 evaluable patients relapsed: one after TAM and three after BAM. In all, 46 other children transplanted in CR beyond CR1 were studied for sequelae. Long-term side effects were more frequent in TAM vs BAM. In children with ALL, busulfan may be a good alternative to TBI to improve the quality of life.Bone Marrow Transplantation (2004) 34, 667-673. doi:10.1038/sj.bmt.1704605 Published online 6 September 2004 [ABSTRACT FROM AUTHOR]

A serial urodynamic study was performed in 491 patients with uterine cancer following radical hysterectomy (RH) involving postoperative pelvic radiation (RH+RT) and extended hysterectomy (EH) for 10 years after these respective treatments. The following evidence is presented: (1) increased volume of residual urine and sensory impairment occurred 1-2 months after radical hysterectomy with or without radiation, but was rarely seen in the EH group: (2) increased residual urine volume in the RH group gradually subsided 1-3 years after the treatment, while the RH+RT treatment resulted in a slight reduction: (3) late maximum cytometric capacity in the EH and RH groups remained stable throughout the study, but the RH+RT group showed a lower capacity ( P<0.05) than the EH group, except in one set of determinations. (4) a high incidence of low bladder compliance in the RH group at 1-2 months decreased thereafter, whereas in the RH+RT group bladder compliance remained poor (23%) up to 7-10 years after treatment. In the EH group low bladder compliance was rarely seen: (5) sensory impairment, urinary incontinence and difficulty on urination remained unimproved in many patients in the RH+RT group, while the incidence of subsequent urological operations in the EH group was lower ( P<0.05) than in the RH+RT group. Based on these findings, EH appears to be more beneficial for the retention of normal bladder function and radical hysterectomy with postoperative radiation results in deterioration of bladder activity. [ABSTRACT FROM AUTHOR]

The whole brains of mice were irradiated with 250 kVp X-rays at 120 rads min (1.6 mm Cu HVL, TSD 50 cm), and a histological study was carried out. The dose range of X-irradiation was from 1,300 to 2,500 rads, i.e., 1,300, 1,500, 1,750, 2,000, and 2,500 rads. Eighty-six mice were used for histological examination. For microscopic examination, the mice were killed at regular postirradiation intervals between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. The brains were removed immediately thereafter, fixed in Bouin's solution, and embedded in paraffin. A histological examination was performed by a morphometric estimation of vascular lesions, in which the degree of the damage to the arterial system was scored in whole serial brain sections. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectatic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large arteries, were observed. Dose-dependent incidence of the fibrinoid necrosis increased between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 to 87 weeks, and can be used to quantify the vessel injury, and that fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis. [ABSTRACT FROM AUTHOR]

We studied the prevalence of chronic liver diseases, including hepatitis C virus (HCV) and hepatitis B virus (HBV) infection, as late effects of therapeutic regimens against childhood malignancies in Japan. Patients were long-time survivors of acute lymphoblastic leukemia (ALL), acute non-lymphoblastic leukemia (ANLL), non-Hodgkin's lymphoma (NHL), neuroblastoma, and osteosarcoma, who had been treated and completed the Children's Cancer and Leukemia Study Group (CCLSG) protocols for more than 6 months at CCLSG participating institutions. The study was initially done in 1993, and as a follow-up study using a retrospective questionnaire in 1997. The overall prevalence of HCV infection in the 1993 study was 8.1% of 443 children. Among those long-term survivors in the 1993 study, 36 (8.1%) children (24 with ALL, 6 with ANLL, 2 with NHL, and 4 others) showed liver dysfunction. The details of the HCV-positive long-term survivors were 26 (13.3%) with ALL, 4 (12.9%) with ANLL, 1 (2%) with NHL, and 5 (3%) with others. The overall prevalence of HCV infection in the 1997 study at the same institutions was 0.6%. Only a slight reduction (5.6%) of HCV antibody positivity was noted in the 1997 follow-up study, while marked reduction (77.2%) of chronic liver disorders was noted during the same follow-up period in 623 children. The high frequency of HCV hepatitis among ALL children is thought to be related to frequent blood transfusions. The 1997 study is the lowest reported prevalence of HCV hepatitis among children with leukemia and malignant diseases. [ABSTRACT FROM AUTHOR]