Effects of a self-affirmation intervention on responses to bowel cancer screening information.

OBJECTIVE: To investigate the effect of two brief self-affirmation interventions, immediately prior to reading standard information about bowel cancer screening, on state anxiety, message acceptance and behavioural intention to screen for bowel cancer. METHODS: 242 adults aged 49 were randomised to one of two self-affirmation interventions (health or values) or one of two control conditions, before reading an NHS England bowel cancer screening leaflet. Participant friend and family history of bowel cancer, state anxiety, message acceptance, behavioural intention to screen, trait self-esteem and spontaneous self-affirmation were measured. Data were analysed using between-participants analysis of variance, planned contrasts and moderated regression. RESULTS: No main effects of experimental condition on levels of state anxiety, message acceptance and behavioural intention were found. However, planned contrasts showed participants who self-affirmed about their health or values (conditions-collapsed) were significantly less anxious and reported significantly higher behavioural intentions compared to participants in the controls (conditions-collapsed). Irrespective of condition, higher levels of spontaneous self-affirmation and trait self-esteem were correlated with lower anxiety, higher intentions, and message acceptance. CONCLUSION: There was some evidence of the effect of health-based self-affirmation on lowering anxiety; however, further research is needed to explore the effectiveness of different self-affirmation interventions in larger samples.

Effects of a modified invitation letter to follow-up colonoscopy for bowel cancer detection.

OBJECTIVE: To investigate whether modifications made to the current National Health Service (NHS) invitation letter for follow-up colonoscopy examination affect participant state anxiety and behavioural intentions to attend. METHODS: Five hundred and thirty-eight adults of bowel cancer-eligible screening age (56-74) were randomized to receive the current NHS invitation letter or the modified version of the letter as a hypothetical scenario. Modifications to the letter included fewer uses of the term cancer and awareness of alternative screening options. The history of the colonoscopy invitation, anticipated state anxiety, behavioural intention to attend the nurse appointment, and colonoscopy concerns upon reading the letter were measured. RESULTS: Behavioural intentions were high in both conditions; however, participants reading the current letter reported significantly higher behavioural intentions compared to the modified letter. There was no main effect of previous invite status or interaction between previous invite status and letter condition on behavioural intentions. However, the effect of the letter on levels of anxiety depended on the participant's invitation history. Those never invited for a colonoscopy were more anxious when reading the modified letter compared to the current letter. Conversely, previous colonoscopy invitees were less anxious following reading the modified letter than those reading the current letter. Those never invited for a colonoscopy were more concerned about embarrassment and test invasiveness. All findings remained the same when controlling for age and education. CONCLUSION: Modifications to the invitation letter were not beneficial to levels of screening intention or anxiety.

The role of native cysteine residues in the oligomerization of KCNQ1 channels.

KCNQ1, the major component of the slow-delayed rectifier potassium channel, is responsible for repolarization of cardiac action potential. Mutations in this channel can lead to a variety of diseases, most notably long QT syndrome. It is currently unknown how many of these mutations change channel function and structure on a molecular level. Since tetramerization is key to proper function and structure of the channel, it is likely that mutations modify the stability of KCNQ1 oligomers. Presently, the C-terminal domain of KCNQ1 has been noted as the driving force for oligomer formation. However, truncated versions of this protein lacking the C-terminal domain still tetramerize. Therefore, we explored the role of native cysteine residues in a truncated construct of human KCNQ1, amino acids 100-370, by blocking potential interactions of cysteines with a nitroxide based spin label. Mobility of the spin labels was investigated with continuous wave electron paramagnetic resonance (CW-EPR) spectroscopy. The oligomerization state was examined by gel electrophoresis. The data provide information on tetramerization of human KCNQ1 without the C-terminal domain. Specifically, how blocking the side chains of native cysteines residues reduces oligomerization. A better understanding of tetramer formation could provide improved understanding of the molecular etiology of long QT syndrome and other diseases related to KCNQ1.

Increased Breast and Colorectal Cancer Risk in Type 2 Diabetes: Awareness Among Adults With and Without Diabetes and Information Provision on Diabetes Websites.

BACKGROUND: People with type 2 diabetes mellitus (T2DM) have a higher risk of developing breast and bowel cancers but are less likely to participate in cancer screening. PURPOSE: Two interlinked studies examined public awareness of the fact that T2DM increases breast and bowel cancer risk, and provision of this information on diabetes websites. METHODS: Study-1: phase-1 surveyed awareness of T2DM-increased cancer risk in a nationally-representative British sample aged 50-74 (N = 1,458) and compared respondents with and without T2DM (n = 125 vs. n = 1,305); phase-2 surveyed an additional exclusively T2DM sample (N = 319). Study-2: High-ranking diabetes websites (N = 25) were reviewed to determine the rate of inclusion of cancer risk and cancer screening information in evident sections about diabetes-related health conditions. RESULTS: A low proportion of respondents were aware that T2DM increases risk of breast (13.7%) and bowel (27.6%) cancers, compared to much higher awareness of other diabetes-related conditions such as sight loss (82.2%) and foot problems (81.8%). Respondents with T2DM were significantly more likely than those without T2DM to be aware of all the surveyed diabetes-related health conditions (e.g., sight loss, OR: 3.14, 95%CI: 1.61-6.15; foot problems, OR: 2.58, 95%CI: 1.38-4.81), except breast (OR: 0.82, 95%CI: 0.46-1.45) and bowel (OR: 0.95, 95%CI: 0.63-1.45) cancer, for which awareness was equally low among people with and without T2DM. Few diabetes websites with a section on diabetes-related health conditions included cancer in this section (n = 4/19), and fewer still included cancer screening among any noted cancer-protective behaviors (n = 2/4). CONCLUSIONS: There is low public awareness that T2DM increases the risk of developing breast and bowel cancers, even among people with T2DM, which may be partly due to limited information provision regarding T2DM-increased cancer risk from diabetes care providers and organizations.

People with type 2 diabetes (T2D) have a higher risk of developing breast and bowel cancers. Despite this, they are less likely to participate in cancer screening, which can improve survival from cancer. We addressed two questions. Are people aware that T2D increases the risk of breast and bowel cancer? Are people being told about this by diabetes care providers and organizations? We surveyed a large representative sample of the British public (aged 50­74). We also reviewed key information about diabetes-related health problems provided on 25 top-ranking diabetes websites. There were three main findings. (1) Relatively few people knew that T2D increases the risk of breast and bowel cancer. In contrast, many people knew that T2D increases the risk of other conditions like sight loss, foot problems, and heart disease. (2) Awareness of higher cancer risk was equally low among people with T2D and those without. In contrast, knowledge of other diabetes-related conditions (e.g., sight loss, foot problems) was higher among people with T2D than those without. (3) Few websites included cancer in their key information about diabetes-related health problems. In contrast, nearly all the diabetes websites listed the more well-known risks of sight loss, foot problems, and heart disease.

Barriers to colonoscopy in UK colorectal cancer screening programmes: Qualitative interviews with ethnic minority groups.

OBJECTIVE: People from ethnic minority backgrounds are less likely to attend colonoscopy, following faecal immunochemical test screening, and are more likely to be diagnosed with colorectal cancer at an advanced stage as a result. The aim of this research was to explore the barriers and facilitators to attending colonoscopy, perceived by ethnic minority groups living in the United Kingdom. METHODS: Semi-structured online and telephone interviews were conducted with thirty men and women of Black-African (n = 5), Black-Caribbean (n = 5), South Asian (n = 10) and White British (n = 10) descent. Participants were eligible for screening, but had not necessarily been invited for colonoscopy. All interviews were conducted in the participant's first language and were assessed using Framework-analysis, in line with a conceptual framework developed from previous interviews with healthcare professionals. RESULTS: Five thematic groups of barriers and facilitators were developed: 'Locus of control', 'Cultural attitudes and beliefs', 'Individual beliefs, knowledge and personal experiences with colonoscopy and cancer', 'Reliance on family and friends' and 'Health concerns'. Differences were observed, between ethnic groups, for: 'Locus of control', 'Cultural attitudes and beliefs' and 'Reliance on family and friends'. Black and South Asian participants frequently described the decision to attend colonoscopy as lying with 'God' (Muslims, specifically), 'the doctor', or 'family' (Locus of control). Black and South Asian participants also reported relying on friends and family for 'language, transport and emotional support' (Reliance on family and friends). Black-African participants, specifically, described cancer as 'socially taboo' (Cultural attitudes and beliefs). CONCLUSIONS: The results highlight several targets for culturally-tailored interventions to make colonoscopy more equitable.

Barriers and facilitators to colonoscopy for cancer detection: patient and practitioner perspectives.

OBJECTIVE: To further understand the barriers and facilitators to attending colonoscopy examination following a positive routinely offered stool test result, from the perspective of patients and Specialist Screening Practitioners (SSPs). METHODS: Qualitative semi-structured interviews were conducted. Participants (N = 32) were patients (n = 20) who, as part of the Bowel Cancer Screening Programme (BCSP) in England, were invited to attend a colonoscopy examination, and SSPs (n = 12), who worked for the BCSP in England. Framework analysis included inductive and deductive coding. RESULTS: Anxiety was as a key barrier cited by patients and SSPs, arising from the moment the patient received the invitation letter. Notably, procedural-related anxieties centred upon the fear of pain and discomfort and test invasiveness. The role of family, friends and the SSP were recognised by patients and SSPs to facilitate participation. Many patients, yet not SSPs, emphasised an obligation to attend all medical test invitations. CONCLUSION: Practically orientated strategies suggested by patients and SSPs address the patient barriers identified. These include earlier information to patients on the option of sedation for pain relief, earlier notification of potential financial support for patients unable to fund their own travel costs, and fewer uses of the term cancer within written materials.

Barriers and facilitators to colonoscopy following fecal immunochemical test screening for colorectal cancer: A key informant interview study.

OBJECTIVES: People who are referred for colonoscopy, following an abnormal colorectal cancer (CRC) screening result, are at increased risk of CRC. Despite this, many individuals decline the procedure. The aim of this study was to investigate why. METHODS: As little is currently known about non-attendance at follow-up colonoscopy, and follow-up of abnormal screening results is a nurse-led process, we decided to conduct key informant interviews with Specialist Screening Practitioners ([SSPs] nurses working in the English Bowel Cancer Screening Program). Interviews were conducted online. Transcripts were assessed using inductive and deductive coding techniques. RESULTS: 21 SSPs participated in an interview. Five main types of barriers and facilitators to colonoscopy were described, namely: Sociocultural, Practical, Psychological, Health-related and COVID-related. Key psychological and sociocultural factors included: 'Fear of pain and discomfort associated with the procedure' and 'Lack of support from family and friends'. Key practical, health-related and COVID-related factors included: 'Family and work commitments', 'Existing health conditions as competing priorities' and 'Fear of getting COVID-19 at the hospital'. CONCLUSIONS: A range of barriers and facilitators to follow-up colonoscopy exist. Future studies conducted with patients are needed to further explore barriers to colonoscopy. PRACTICE IMPLICATIONS: Strategies to reduce non-attendance should adopt a multifaceted approach.

Barriers to flexible sigmoidoscopy colorectal cancer screening in low uptake socio-demographic groups: A systematic review.

OBJECTIVE: To synthesise qualitative evidence related to barriers and facilitators of flexible sigmoidoscopy screening (FSS) intention and uptake, particularly within low socio-demographic uptake groups. FSS uptake is lower amongst women, lower socio-economic status (SES), and Asian ethnic groups within the United Kingdom (UK) and United States of America. METHODS: A total of 12 168 articles were identified from searches of four databases: EMBASE, MEDLINE, PsycINFO and Web of Science. Eligibility criteria included: individuals eligible to attend FSS and empirical peer-reviewed studies that analysed qualitative data. The Critical Appraisal Skills Program tool evaluated the methodological quality of included studies, and thematic synthesis was used to analyse the data. RESULTS: Ten qualitative studies met the inclusion criteria. Key barriers to FSS intention and uptake centred upon procedural anxieties. Women, including UK Asian women, reported shame and embarrassment, anticipated pain, perforation risk, and test preparation difficulties to elevate anxiety levels. Religious and cultural-influenced health beliefs amongst UK Asian groups were reported to inhibit FSS intention and uptake. Competing priorities, such as caring commitments, particularly impeded women's ability to attend certain FSS appointments. The review identified a knowledge gap concerning factors especially associated with FSS participation amongst lower SES groups. CONCLUSIONS: Studies mostly focussed on barriers and facilitators of intention to participate in FSS, particularly within UK Asian groups. To determine the barriers associated with FSS uptake, and further understand how screening intention translates to behaviour, it is important that future qualitative research is equally directed towards factors associated with screening behaviour.

Rationale and Models for Career Advancement Sponsorship in Academic Medicine: The Time Is Here; the Time Is Now.

The business community has honed the concept of sponsorship and promulgated its utility for harnessing the talent of high-performing women and minorities whose contributions often go unrecognized within organizations. In recent years, academic medicine has begun to do the same. Whereas mentorship often centers on personal and professional development (e.g., skill building and goal setting), sponsorship focuses on enhancing the visibility, credibility, and professional networks of talented individuals. For upward career mobility, mentorship is limited in scope. Sponsorship, on the other hand, directly targets career advancement and is anchored in the sponsor's awareness of organizational structures and critical professional opportunities for junior faculty. Men are more likely to garner sponsors informally, and these sponsors tend to be male. Existing disparities between male and female medical faculty in achievement of academic rank and leadership roles, compensation, and research support suggest that high-performing women have a visibility gap. Such systemic inequity reflects a suboptimal business model that limits organizational potential. Formal sponsorship programs that match women with senior leaders facilitate access to beneficial relationships and institutionalize the value of equal opportunity. In this Perspective, the authors describe two successful sponsorship models that exist within academic medicine, the Society of General Internal Medicine's Career Advising Program and MD Anderson Cancer Center's Leaders' Sponsorship Program. They issue a call to action for much broader implementation of sponsorship programming to cultivate the advancement of all talented medical faculty and provide recommendations for such endeavors.

Provider and Patient Gender Influence on Timing of Do-Not-Resuscitate Orders in Hospitalized Patients with Cancer.

BACKGROUND: End-of-life decisions and advance directives require timely physician-patient discussions but barriers exist to these discussions. OBJECTIVE: To evaluate the influence of physician and patient gender on the timing of inpatient do-not-resuscitate (DNR) orders. DESIGN: Retrospective cohort study. SETTING/SUBJECTS: All adult patients (≥18 years) with cancer who received inpatient DNR orders at The University of Texas MD Anderson Cancer Center between January 2011 and December 2013. MEASUREMENTS: Gender interaction between physicians and patients towards timing of the DNR order. RESULTS: We identified 4,157 unique patients with a cancer diagnosis. These patients were treated by 353 physicians, of whom 123 (34.8%) were females and 230 (65.2%) were males. Multivariate analysis showed female patients were 1.3 times more likely to have early DNR orders written during hospital admission than were male patients (odds ratio [OR] 1.27; 95% confidence interval [CI] 1.07-1.50). When comparing gender interaction between physicians and patients, our results showed that female physicians were 1.5 times more likely to write early DNR orders with their female patients than for their male patients (OR, 1.48; 95% CI, 1.13-1.94). Same gender physician-patient dyads were not found between male physician and their patients (OR, 1.09; 95% CI, 0.91-1.31). Higher age, more comorbid conditions, and progression of diseases were also associated with early DNR orders (all p < 0.01). CONCLUSION: Female patients are more likely to receive early DNR orders from their female physicians. Gender and gender interaction between physician and patients may potentially influence the timing of receiving DNR order.

Lymph node grafting in the treatment of upper limb lymphoedema: a clinical trial.

BACKGROUND: Microvascular lymph node transfer has been shown to improve the severity of lymphoedema. However, microvascular surgery is not suitable for all patients. Simple lymph node grafting does not require general anaesthetic or significant surgical resources and is a technique that has been tested in animal models only until this point. Our hypothesis is that the transplanted lymph nodes integrate into the lymphovascular system and function as a 'pump', directly pumping interstitial fluid back into the venous system. METHODS: We hypothesized that lymph node grafting would improve lymphoedema with a low risk of complications. The procedure was performed in a day surgery setting under local anaesthetic with sedation. Two lymph nodes were harvested from the groin and grafted into subcutaneous tissue on the volar aspect of the affected limb at supratrochlear and wrist levels. RESULTS: We found that nine of 10 patients reported a subjective and/or functional improvement in their lymphoedema, including an improvement in hand function and tissue feel. Truncal cone calculation volumes showed an overall decrease in affected limb volume of 89.7 mL (standard deviation = 136.5). Furthermore, follow-up lymphoscintigram imaging on one patient demonstrated viability and function of the implanted node. CONCLUSIONS: We conclude that this is a safe procedure and should be further investigated as an alternative to a microsurgical procedure as a treatment for upper limb lymphoedema. Further research with a larger sample size is needed to confirm the findings of this pilot study.

Operating theatre time, where does it all go? A prospective observational study.

OBJECTIVE: To assess the accuracy of surgeons and anaesthetists in predicting the time it will take them to complete an operation or procedure and therefore explain some of the difficulties encountered in operating theatre scheduling. DESIGN: Single centre, prospective observational study. SETTING: Plastic, orthopaedic, and general surgical operating theatres at a level 1 trauma centre serving a population of about 370,000. PARTICIPANTS: 92 operating theatre staff including surgical consultants, surgical registrars, anaesthetic consultants, and anaesthetic registrars. INTERVENTION: Participants were asked how long they thought their procedure would take. These data were compared with actual time data recorded at the end of the case. PRIMARY OUTCOME MEASURE: Absolute difference between predicted and actual time. RESULTS: General surgeons underestimated the time required for the procedure by 31 minutes (95% confidence interval 7.6 to 54.4), meaning that procedures took, on average, 28.7% longer than predicted. Plastic surgeons underestimated by 5 minutes (-12.4 to 22.4), with procedures taking an average of 4.5% longer than predicted. Orthopaedic surgeons overestimated by 1 minute (-16.4 to 14.0), with procedures taking an average of 1.1% less time than predicted. Anaesthetists underestimated by 35 minutes (21.7 to 48.7), meaning that, on average, procedures took 167.5% longer than they predicted. The four specialty mean time overestimations or underestimations are significantly different from each other (P=0.01). The observed time differences between anaesthetists and both orthopaedic and plastic surgeons are significantly different (P<0.05), but the time difference between anaesthetists and general surgeons is not significantly different. CONCLUSION: The inability of clinicians to predict the necessary time for a procedure is a significant cause of delay in the operating theatre. This study suggests that anaesthetists are the most inaccurate and highlights the potential differences between specialties in what is considered part of the "anaesthesia time."

NRF2 deficiency reduces life span of mice administered thoracic irradiation.

Subsets of cancer survivors who have been subjected to thoracic irradiation face the prospect of developing pulmonary injury. Radiation-induced pulmonary fibrosis is an insidious injury that presents 6 to 24 months after irradiation and continues to progress over a period of years. TGF-ß and reactive oxygen species contribute significantly to the pathogenesis of this injury. The transcription factor NRF2 controls antioxidant gene expression and therefore regulates the cellular oxidant burden. This work demonstrates an additional paradigm for NRF2: suppression of TGF-ß-mediated signaling, assessed by measuring expression of a surrogate TGF-ß1 target gene (PAI-1) in lung fibroblasts. Thoracic irradiation of Nfe2l2(-/-) mice resulted in rapid expression of PAI-1 and FSP-1 compared to irradiated wild-type mice. Examination of lung tissue 16 weeks after thoracic irradiation of Nfe2l2(-/-) mice revealed the presence of distended alveoli and decreased numbers of alveoli compared to wild-type mice. Suppression of NRF2 expression shortened life span in mice administered 16 Gy to the thorax. Nfe2l2(+/-) and Nfe2l2(-/-) mice exhibited a mean life span of 176 days compared to wild-type mice, which lived an average of 212 days. These novel results identify NRF2 as a susceptibility factor for the development of late tissue injury.

Haemophilus influenzae lysate induces aspects of the chronic obstructive pulmonary disease phenotype.

Nontypeable Haemophilus influenzae (NTHi) commonly colonizes the lower airways of patients with chronic obstructive pulmonary disease (COPD). Whether it contributes to COPD progression is unknown. Here, we determined which aspects of the COPD phenotype can be induced by repetitive exposure to NTHi products. Mice were exposed weekly to an aerosolized NTHi lysate, and inflammation was evaluated by measurement of cells and cytokines in bronchoalveolar lavage fluid (BALF) and immunohistochemical staining; structural changes were evaluated histochemically by periodic acid fluorescent Schiff's reagent, Masson's trichrome, and Picrosirius red staining; mucin gene expression was measured by quantitative RT-PCR; and the role of TNF-alpha was examined by transgenic airway overexpression and use of an inhibitory antibody. NTHi lysate induced rapid activation of NF-kappaB in airway cells and increases of inflammatory cytokines and neutrophils in BALF. Repetitive exposure induced infiltration of macrophages, CD8+ T cells, and B cells around airways and blood vessels, and collagen deposition in airway and alveolar walls, but airway mucin staining and gel-forming mucin transcripts were not increased. Transgenic overexpression of TNF-alpha caused BALF neutrophilia and inflammatory cell infiltration around airways, but not fibrosis, and TNF-alpha neutralization did not reduce BALF neutrophilia in response to NTHi lysate. In conclusion, NTHi products elicit airway inflammation in mice with a cellular and cytokine profile similar to that in COPD, and cause airway wall fibrosis but not mucous metaplasia. TNF-alpha is neither required for inflammatory cell recruitment nor sufficient for airway fibrosis. Colonization by NTHi may contribute to the pathogenesis of small airways disease in patients with COPD.

Genetic susceptibility to late normal tissue injury.

The outcome of all cancer therapies, including radiation, has greatly improved in the last 25 years, resulting in a doubling of the number of long-term cancer survivors. However, a subset of these survivors incurs adverse chronic side effects in unavoidably irradiated normal tissues, persisting long after treatment and compromising the quality of life of these patients. Interpatient variability in normal tissue radiation response is well documented and suggested to be under genetic control. Fibrosis, a clinically significant late effect in many irradiated tissues that results in tissue remodeling and loss of function, is a complex genetic trait making identification of the underlying genes difficult. Current clinical and animal studies are providing information on the genetics and molecular basis of late normal tissue injury in the radiation therapy setting, bringing us closer to our dual goal of individualizing treatment by genetic profiling and improving the quality of life of long-term survivors.

Reduction of pulmonary compliance found with high-resolution computed tomography in irradiated mice.

PURPOSE: To demonstrate that high-resolution computed tomography (CT) can be used to quantify loss of pulmonary compliance in irradiated mice. METHODS AND MATERIALS: Computed tomography images of three nonirradiated (controls) and three irradiated mice were obtained 200 days after a single dose of 16-Gy Co (60) thoracic irradiation. While intubated, each animal was imaged at static breath-hold pressures of 2, 10, and 18 cm H2O. A deformable image registration algorithm was used to calculate changes in air volume between adjacent-pressure CT image pairs (e.g., 2 and 10 cm H2O), and functional images of pulmonary compliance were generated. The mass-specific compliance was calculated as the change in volume divided by the pressure difference between the 2 image sets and the mass of lung tissue. RESULTS: For the irradiated mice, the lung parenchyma mean CT values ranged from -314 (+/- 11) Hounsfield units (HU) to -378 (+/- 11) HU. For the control mice, the mean CT values ranged from -549 (+/- 11) HU to -633 (+/- 11) HU. Irradiated mice had a 60% (45, 74%; 95% confidence interval) lower mass-specific compliance than did the controls (0.039 [+/- 0.0038] vs. 0.106 [+/- 0.0038] mL air per cm H2O per g lung) from the 2-cm to 10-cm H2O CT image pair. The difference in compliance between groups was less pronounced at the higher distending pressures. CONCLUSION: High-resolution CT was used to quantify a reduction in mass-specific compliance following whole lung irradiation in mice. This small animal radiation injury model and assay may be useful in the study of lung injury.

Quantification of bleomycin-induced murine lung damage in vivo with micro-computed tomography.

RATIONALE AND OBJECTIVES: We explored noninvasive, in vivo cone-beam microcomputed tomography (micro-CT) to visualize and quantify fibrotic and inflammatory damage over the entire lung volume of mice. MATERIALS AND METHODS: We used bleomycin to induce pulmonary damage in vivo and compared the results from micro-CT with histologic measurements. Ten C57BL/6 mice were given 5 U/kg bleomycin intratracheally. Seven surviving mice were scanned with micro-CT before administration of bleomycin, and again before sacrifice. The resulting images were analyzed for lung volume measurements. After the final scan, all lungs were examined histologically and pulmonary damage was quantified. Damaged lung tissue regions were matched between micro-CT images and histologic sections for each mouse. RESULTS: The percent lung damage calculated from micro-CT and histology were correlated (r(2) = 0.49, r = 0.64 with P = 0.12), and the means of their respective distributions were not different (P > 0.05). CONCLUSION: This study shows that micro-CT is a promising alternative to predicting lung damage caused by bleomycin. CT image volumes of the thorax allow for global tissue sampling, which may be useful when following nonuniform lung damage that can occur from intratracheal administration of bleomycin.

Mutagen sensitivity may predict lung protection by amifostine for patients with locally advanced non-small cell lung cancer treated by chemoradiotherapy.

Amifostine (AMF) has been shown to protect some normal tissues from acute effects of radiation therapy +/- chemotherapy. We enrolled 62 patients in a randomized study investigating the efficacy of AMF: 31 had concurrent chemoradiation for non-small cell lung cancer and 31 had the same treatment + AMF. AMF reduced the frequency and severity of esophagitis, pneumonitis, and neutropenic fever. We have tried to identify patients who get more benefit from AMF by checking their DNA repair capability of normal cells. It was hypothesized that DNA repair capacity from patients' lymphocytes damaged by bleomycin could predict their normal tissue sensitivity to chemoradiation and could be protected by AMF. Forty-six of the 62 patients provided pretreatment blood for assessment of mutagen sensitivity (MS) using a peripheral lymphocyte assay that infers DNA repair capacity from cellular damage remaining after in vitro mutagenic exposure and recovery. Bleomycin-induced chromosome breaks in 50 metaphases were counted and expressed as the mean number of breaks per cell. Patients with an average of more than one break/cell were deemed to exhibit the MS phenotype. Data analysis used Pearson's chi-square and Kaplan-Meier survival function estimates with Strata 8.2 statistical software. The Log-rank test was used to assess the equality of survival function using a P value of .05. Twelve patients (10 AMF, 2 control) exhibited the MS phenotype. The remaining 34 patients (13 AMF, 21 control) were considered to have normal DNA repair. There were no significant differences in overall survival, disease specific survival, or local control by MS. Those with high MS had shorter distant metastasis-free survival compared with low MS patients ( P = .029). There were no differences in severe esophagitis or neutropenic fever by MS. Both high and low MS patients from the control group developed severe lung fibrosis compared with five of 21 who had AMF ( P = .025). The incidence of grade 3/4 lung fibrosis was two of 10 with AMF compared with two of two in the control group ( P = .025) with higher MS. Higher MS was associated with shorter distant metastasis-free survival and more frequent grade 3/4 lung fibrosis. AMF reduced the incidence of grade 3/4 lung fibrosis among higher MS. These data suggest that MS might help identify subgroups of patients who could receive more benefit from AMF with respect to lung damage.