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Sleep-disordered breathing and excessive sleepiness may be more common in commercial vehicle drivers than in the general population. The relative importance of factors causing excessive sleepiness and accidents in this population remains unclear. We measured the prevalence of excessive sleepiness and sleep-disordered breathing and assessed accident risk factors in 2,342 respondents to a questionnaire distributed to a random sample of 3,268 Australian commercial vehicle drivers and another 161 drivers among 244 invited to undergo polysomnography. More than half (59.6%) of drivers had sleep-disordered breathing and 15.8% had obstructive sleep apnea syndrome. Twenty-four percent of drivers had excessive sleepiness. Increasing sleepiness was related to an increased accident risk. The sleepiest 5% of drivers on the Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire had an increased risk of an accident (odds ratio [OR] 1.91, p = 0.02 and OR 2.23, p < 0.01, respectively) and multiple accidents (OR 2.67, p < 0.01 and OR 2.39, p = 0.01), adjusted for established risk factors. There was an increased accident risk with narcotic analgesic use (OR 2.40, p < 0.01) and antihistamine use (OR 3.44, p = 0.04). Chronic excessive sleepiness and sleep-disordered breathing are common in Australian commercial vehicle drivers. Accident risk was related to increasing chronic sleepiness and antihistamine and narcotic analgesic use. [ABSTRACT FROM AUTHOR]

Purpose: We sought to evaluate the prognostic impact of prostate-specific antigen (PSA) at 6 months after completion of radiotherapy (RT) in patients treated with RT alone, RT plus short-term (st; 3-6 months), and RT plus long-term (lt; 24-36 months) androgen-deprivation therapy (ADT)., Patients and Methods: Individual patient data were obtained from 16 randomized trials evaluating RT ± ADT for localized prostate cancer (PCa) between 1987 and 2011. The lowest PSA recorded within 6 months after RT completion was identified and categorized as < or ≥0.1 ng/mL. The primary outcomes were metastasis-free survival (MFS), PCa-specific mortality (PCSM), and overall survival (OS), from 12 months after random assignment., Results: Ninety-eight percent (n = 2,339/2,376) of patients allocated to RT alone, 84% (n = 4,756/5,658) allocated to RT + stADT, and 77% (n = 1,258/1,626) allocated to RT + ltADT had PSA ≥0.1 ng/mL within 6 months after completing RT. PSA ≥0.1 ng/mL was associated with lower MFS and OS and higher PCSM among patients allocated to RT ± ADT (RT - MFS: hazard ratio [HR], 2.24 [95% CI, 1.21 to 4.16]; PCSM: subdistribution hazard ratio [sHR], 1.82 [0.51 to 6.49]; OS: HR, 1.72 [0.97 to 3.05]; RT + stADT - MFS: HR, 1.27 [1.12 to 1.44]; PCSM: sHR, 2.10 [1.52 to 2.92]; OS: HR, 1.26 [1.11 to 1.44]; RT + ltADT - MFS: HR, 1.58 [1.27 to 1.96]; PCSM: sHR, 1.97 [1.11 to 3.49]; OS: HR, 1.59 [1.27 to 1.99]). Five-year MFS rates among patients allocated to RT, RT + stADT, and RT + ltADT were 91% versus 79%, 83% versus 76%, and 87% versus 74%, respectively, based on PSA < or ≥0.1 ng/mL., Conclusion: PSA ≥0.1 ng/mL within 6 months after RT completion was prognostic for lt outcomes in patients treated with RT ± ADT for localized PCa. This can be used to counsel patients treated with RT ± ADT and in guiding clinical trial design evaluating novel systemic therapies with RT + ADT as well as (de)intensification strategies.

Background: The efficacy and safety of primary re-irradiation for MSCC are not known. Our aim was to establish the efficacy and safety of biologically effective dose-based re-irradiation., Methods: Patients presenting with MSCC at a previously irradiated spine segment, and not proceeding with surgical decompression, were eligible. A 3 Gray per fraction experimental schedule (minimum 18 Gy/6 fractions, maximum 30 Gy/10 fractions) was used, delivering a maximum cumulative spinal dose of 100 Gy 2 if the interval since the last radiotherapy was within 6 months, or 130 Gy 2 if longer. The primary outcome was a change in mobility from week 1 to week 5 post-treatment, as assessed by the Tomita score. The RTOG SOMA score was used to screen for spinal toxicity, and an MRI performed to assess for radiation-induced myelopathy (RIM)., Results: Twenty-two patients were enroled, of whom eleven were evaluable for the primary outcome. Nine of eleven (81.8%) had stable or improved Tomita scores at 5 weeks. One of eight (12.5%) evaluable for late toxicity developed RIM., Conclusions: Re-irradiation is an efficacious treatment for MSCC. There is a risk of RIM with a cumulative dose of 120 Gy 2 ., Clinical Trial Registration: Cancer Trials Ireland (ICORG 07-11); NCT00974168., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: The purpose of this study was to evaluate the interobserver variability in the contouring of the gross tumor volume (GTV) on magnetic resonance (MR) imaging and computed tomography (CT) for colorectal liver metastases in the setting of SABR., Methods and Materials: Three expert radiation oncologists contoured 10 GTV volumes on 3 MR imaging sequences and on the CT image data set. Three metrics were chosen to evaluate the interobserver variability: the conformity index, the DICE coefficient, and the maximum Hausdorff distance (HDmax). Statistical analysis of the results was performed using a 1-sided permutation test., Results: For all 3 metrics, the MR liver acquisition volume acquisition (MR LAVA) showed the lowest interobserver variability. Analysis showed a significant difference ( P < .01) in the mean DICE, an overlap metric, for MR LAVA (0.82) and CT (0.74). The HDmax that highlights boundary errors also showed a significant difference ( P  = .04) with MR LAVA having a lower mean HDmax (7.2 mm) compared with CT (5.7 mm). The mean HDmax for both MR single shot fast spin echo (SSFSE) (19.3 mm) and diffusion weighted image (9.5 mm) showed large interobserver variability with MR SSFSE having a mean HDmax of 19.3 mm. A volume comparison between MR LAVA and CT showed a significantly higher volume for small GTVs (<5 cm 3 ) when using MR LAVA for contouring in comparison to CT., Conclusions: This study reported the lowest interobserver variability for the MR LAVA, thus indicating the benefit of using MR to complement CT when contouring GTV for colorectal liver metastases., (© 2022 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)

Background: Randomised trials have investigated various androgen deprivation therapy (ADT) intensification strategies in men receiving radiotherapy for the treatment of prostate cancer. This individual patient data meta-analysis of relevant randomised trials aimed to quantify the benefit of these interventions in aggregate and in clinically relevant subgroups., Methods: For this meta-analysis, we performed a systematic literature search in MEDLINE, Embase, trial registries, the Web of Science, Scopus, and conference proceedings to identify trials with results published in English between Jan 1, 1962, and Dec 30, 2020. Multicentre randomised trials were eligible if they evaluated the use or prolongation of ADT (or both) in men with localised prostate cancer receiving definitive radiotherapy, reported or collected distant metastasis and survival data, and used ADT for a protocol-defined finite duration. The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium was accessed to obtain individual patient data from randomised trials. The primary outcome was metastasis-free survival. Hazard ratios (HRs) were obtained through stratified Cox models for ADT use (radiotherapy alone vs radiotherapy plus ADT), neoadjuvant ADT extension (ie, extension of total ADT duration in the neoadjuvant setting from 3-4 months to 6-9 months), and adjuvant ADT prolongation (ie, prolongation of total ADT duration in the adjuvant setting from 4-6 months to 18-36 months). Formal interaction tests between interventions and metastasis-free survival were done for prespecified subgroups defined by age, National Comprehensive Cancer Network (NCCN) risk group, and radiotherapy dose. This meta-analysis is registered with PROSPERO, CRD42021236855., Findings: Our search returned 12 eligible trials that provided individual patient data (10 853 patients) with a median follow-up of 11·4 years (IQR 9·0-15·0). The addition of ADT to radiotherapy significantly improved metastasis-free survival (HR 0·83 [95% CI 0·77-0·89], p<0·0001), as did adjuvant ADT prolongation (0·84 [0·78-0·91], p<0·0001), but neoadjuvant ADT extension did not (0·95 [0·83-1·09], p=0·50). Treatment effects were similar irrespective of radiotherapy dose, patient age, or NCCN risk group., Interpretation: Our findings provide the strongest level of evidence so far to the magnitude of the benefit of ADT treatment intensification with radiotherapy for men with localised prostate cancer. Adding ADT and prolonging the portion of ADT that follows radiotherapy is associated with improved metastasis-free survival in men, regardless of risk group, age, and radiotherapy dose delivered; however, the magnitude of the benefit could vary and shared decision making with patients is recommended., Funding: University Hospitals Seidman Cancer Center, Prostate Cancer Foundation, and the American Society for Radiation Oncology., Competing Interests: Declaration of interests AUK reports personal fees from Varian Medical Systems, ViewRay, and Intelligent Automation; and research support from ViewRay, the American Society for Radiation Oncology, the Prostate Cancer Foundation, and the Jonsson Comprehensive Cancer Center, all outside the submitted work. FYF reports a consulting or advisory role for Astellas, Bayer, BlueEarth Diagnostics, Celgene, EMD Serono, Genentech, Janssen, Myovant, Ryovant, Bristol Myers Squibb, Exact Sciences, Varian, Bluestar Genomics, and Serimmun; and research funding from Zenth Epigenetics. AN reports personal fees from AstraZeneca, outside the submitted work. LS reports personal fees from Sanofi Canada and Varian Medical Systems, outside the submitted work. JAE reports personal fees from Blue Earth, Boston Scientific, AstraZeneca, Taris Biomedical, Merck, Roviant Pharma, and Myovant Sciences. HMS is a member of a clinical trial steering committee for Janssen and reports stock from Radiogel for an inactive role on medical advisory board, all outside of the submitted work. MBR reports personal fees from Amgen, Clovis, Janssen, Bayer, and Abrx; and research support from Janssen and Merck, outside the submitted work. NGN reports research funding from Janssen, Lantheus, and Bayer; and consulting fees from Oncolinea. DES declares personal fees from Janssen, AstraZeneca, and BlueEarth, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aims: To report late toxicity and long-term outcomes of intensity-modulated radiotherapy (IMRT)-based stereotactic ablative body radiotherapy (SABR) in patients with ultra-central lung tumours., Materials and Methods: This is a single-institution retrospective analysis of patients treated with SABR for ultra-central tumours between May 2008 and April 2016. Ultra-central location was defined as tumour (GTV) abutting or involving trachea, main or lobar bronchi. Respiratory motion management and static-field dynamic-IMRT were used, with dose prescribed homogeneously (maximum <120%). Descriptive analysis, Kaplan-Meier method, log-rank test and Cox regression were used to assess outcomes., Results: Sixty-five per cent of patients had inoperable primary non-small cell lung cancer and 35% had lung oligometastases. The median age was 72 (range 34-85) years. The median gross tumour volume and planning target volume (PTV) were 19.6 (range 1.7-203.3) cm 3 and 57.4 (range 7.7-426.6) cm 3 , respectively. The most commonly used dose fractionation was 60 Gy in eight fractions (n = 51, 87.8%). Median BED 10 for D98%PTV and D2%PTV were 102.6 Gy and 115.06 Gy, respectively. With a median follow-up of 26.5 (range 3.2-100.5) months, fatal haemoptysis occurred in five patients (8.7%), of which two were directly attributable to SABR. A statistically significant difference was identified between median BED 3 for 4 cm 3 of airway, for patients who developed haemoptysis versus those who did not (147.4 versus 47.2 Gy, P = 0.005). At the last known follow-up, 50 patients (87.7%) were without local recurrence. Freedom from local progression at 2 and 4 years was 92 and 79.8%, respectively. The median overall survival was 34.3 (95% confidence interval 6.1-61.6) months. Overall survival at 2 and 4 years was 55.1 and 41.2%, respectively., Conclusion: In patients with high-risk ultra-central lung tumours, IMRT-based SABR with homogenous dose prescription achieves high local control, similar to that reported for peripheral tumours. Although fatal haemoptysis occurred in 8.7% of patients, a direct causality with SABR was evident in only 3%. Larger studies are warranted to ascertain factors associated with outcomes, especially toxicity, and identify patients who would probably benefit from this treatment., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: Stereotactic ablative radiation therapy (SABR) is a standard of care for medically inoperable early stage non-small cell lung carcinoma. Tumours greater than 5 cm have been excluded from randomised trials using SABR and, hence, it is not used as a standard for larger lung tumours. However, improvements in radiation therapy techniques and the success of SABR in treatment of early stage disease may allow safe delivery of ablative doses to larger tumours. We analysed our experience with tumours ≥5 cm to determine the efficacy and toxicity profile of SABR in this setting., Materials and Methods: We evaluated survival, control rates, patterns of failure and toxicity in patients with a tumour diameter larger than 5 cm that had no nodal or distant metastases treated with SABR technology. Patients had been treated in two centres since 2009 and were retrospectively analysed. All patients had positron emission tomography staging, were discussed at a tumour board and were documented to have no nodal or distant metastatic disease. Treatment outcomes were analysed using Kaplan-Meier estimates and compared using the Log-rank test. Cox regression was used to investigate the association between the survival outcomes and predictor variables., Results: In total, 86 patients were identified. Six patients had no follow-up imaging. Therefore, 80 patients were available for analysis. All patients were reclassified according to the updated AJCC eighth edition. The median follow-up was 19.6 months. No patients received neoadjuvant or concurrent systemic therapy. One patient received adjuvant systemic therapy. The median age at treatment was 77 years (range 58-91). Eighty-four per cent were stage T3N0M0 and 16% were staged T4N0M0. The median tumour diameter was 5.8 cm (range 5.0-9.3 cm). The median gross tumour volume, measured on a single phase of the respiratory cycle, was 45.7 cm 3 (range 12.1-203.3 cm 3 ). The median overall survival was 20.9 months (95% confidence interval 12.6-29.1 months). One-, 2- and 3-year overall survival was 71%, 48% and 32%, respectively. The median local failure-free survival was 19.5 months (95% confidence interval 14.4-24.6). The median disease-free survival was 15.1 months (95% confidence interval 9.9-20.4 months). Local control at 1, 2 and 3 years was 85% (95% confidence interval 76-94%), 71% (95% confidence interval 58-84%) and 57% (95% confidence interval 40-74%), respectively. Forty-four patients (55%) had any treatment failure (local, mediastinal, intrapulmonary or distant metastases). Out-of-field intrapulmonary disease progression was the most common mode of failure, occurring in 21 patients (26%). Local failure occurred in 19 patients (24%) - alone or in combination with other progression. Distant metastases occurred in 20 patients (25%). Neither histological subtype, tumour size nor gross tumour volume had a statistically significant effect on local failure-free survival. Two patients experienced grade 3 late dyspnoea. There were no other reported grade 3 or higher acute or late toxicities., Conclusion: SABR for larger lung tumours ≥5 cm results in high local control and acceptable survival in patients with medically inoperable large non-small cell lung carcinoma treated with radiation alone. Such patients should be considered for SABR owing to fewer treatment fractions and acceptable toxicity. Local control analysis reveals a sustained pattern of local failure emphasising the need for long-term follow-up. Improvements in technical strategies are required to further improve local control., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Microbial reduction of soluble selenium (Se) or tellurium (Te) species results in immobilization as elemental forms and this process has been employed in soil bioremediation. However, little is known of direct and indirect fungal interactions with Se-/Te-bearing ores. In this research, the ability of Phoma glomerata to effect transformation of selenite and tellurite was investigated including interaction with Se and Te present in sulfide ores from the Kisgruva Proterozoic volcanogenic deposit. Phoma glomerata could precipitate elemental Se and Te as nanoparticles, intracellularly and extracellularly, when grown with selenite or tellurite. The nanoparticles possessed various surface capping molecules, with formation being influenced by extracellular polymeric substances. The presence of sulfide ore also affected the production of exopolysaccharide and protein. Although differences were undetectable in gross Se and Te ore levels before and after fungal interaction using X-ray fluorescence, laser ablation inductively coupled plasma mass spectrometry of polished flat ore surfaces revealed that P. glomerata could effect changes in Se/Te distribution and concentration indicating Se/Te enrichment in the biomass. These findings provide further understanding of fungal roles in metalloid transformations and are relevant to the geomicrobiology of environmental metalloid cycling as well as informing applied approaches for Se and Te immobilization, biorecovery or bioremediation., (© 2020 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

Objective: It has been established that survival and toxicity outcomes in some cancer types could be influenced by haemoglobin (Hb) levels. This study aims to determine if pre-treatment Hb is associated with late toxicity or survival outcomes in prostate cancer., Methods: Data from one Phase III randomised controlled trial and one single arm translational trial were analysed. Patients had localized prostate cancer and received ≥70 Gy radiotherapy and neo-adjuvant androgen deprivation between 1997 and 2013., Results: 302 males were included. Median follow-up was 6.8 years for toxicity and 10.3 years for survival outcomes. Patients with Hb below the reference range were more likely to experience Grade 2-3 late gastrointestinal toxicity than patients with Hb within the range ( p = 0.050). Neither late genitourinary toxicity, erectile function toxicity, prostate-specific antigen relapse free survival nor overall survival of patients were statistically significantly different between groups., Conclusion: Anaemia in prostate cancer is found in the minority of patients and is usually mild. Prostate cancer patients undergoing radiotherapy with low Hb were more likely to experience Grade 2-3 late gastrointestinal toxicity., Advances in Knowledge: This study is one of the first in the published literature to investigate the role of Hb in prostate cancer toxicity and survival. We have found an association between Hb below the reference range and late GI toxicity. Consideration should be given to further investigating patients with iron deficiency anaemia to guide management options and outrule underlying GI pathology before proceeding with radiotherapy treatment.

Background: The optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome., Methods: Patients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx. A change in mobility from baseline to 5 weeks for each patient, was evaluated by a Modified Tomita score: 1 = 'Walk unaided', 2 = 'With walking aid' and 3 = 'Bed-bound'. The margin used to establish non-inferiority was a detrimental change of -0.4 in the mean difference between arms., Results: One-hundred and twelve eligible patients were enrolled. Seventy-three patients aged 30-87 were evaluated for the primary analysis. The 95% CI for the difference in the mean change in mobility scores between arms was -0.12 to 0.6. Since -0.4 is not included in the interval, there is evidence that 10 Gy/SF is non-inferior to 20 Gy/5Fx. One grade 3 AE was reported in the 5Fx arm. Twelve (26%) patients in the 5Fx arm had a Grade 2-3 AE compared with six (11%) patients in the SF arm (p = 0.093)., Conclusion: For mobility preservation, one 10-Gy fraction is non-inferior to 20 Gy in five fractions, in patients with MSCC not proceeding with surgical decompression., Clinical Trial Registration: Cancer Trials Ireland ICORG 05-03; NCT00968643; EU-20952.

Purpose: Body mass index (BMI) is often used to predict surgical difficulty in patients receiving total knee arthroplasty (TKA); however, BMI neglects variation in the central versus peripheral distribution of adipose tissue. We sought to examine whether anthropometric factors, rather than BMI alone, may serve as a more effective indication of surgical difficulty in TKA., Materials and Methods: We prospectively enrolled 67 patients undergoing primary TKA. Correlation coefficients were used to evaluate the associations of tourniquet time, a surrogate of surgical difficulty, with BMI, pre- and intraoperative anthropometric measurements, and radiographic knee alignment. Similarly, Knee Injury and Osteoarthritis Outcome Score (KOOS) was compared to BMI., Results: Tourniquet time was significantly associated with preoperative inferior knee circumference (p=0.025) and ankle circumference (p=0.003) as well as the intraoperative depth of incision at the quadriceps (p=0.014). BMI was not significantly associated with tourniquet time or any of the radiographic parameters or KOOS scores., Conclusions: Inferior knee circumference, ankle circumference, and depth of incision at the quadriceps (measures of peripheral obesity) are likely better predictors of surgical difficulty than BMI. Further study of alternative surgical indicators should investigate patients that may be deterred from TKA for high BMI, despite relatively low peripheral obesity.

Objective:: The aim of this study is to investigate if a handheld ultrasound device (BladderScan® BVI 6100) can accurately measure bladder volumes in prostate radiotherapy (RT) patients., Methods:: A comparison was made of contoured bladder volumes based on treatment planning CT (TPCT) and BladderScan® BVI 6100 ultrasound device in a large prostate RT population. Three bladder volume (BV) measurements were taken using the bladder volume instrument (BVI) device on prostate RT patients immediately prior to TPCT (n = 190). The CT delineation bladder volumes were also recorded. The mean of the three BVI readings (BVI mean ) and the maximum (BVI max ) of the readings were considered for a comparative analysis., Results:: There was a strong positive correlation between the BVI and CT delineated bladder volumes (BVI mean r = 0.825; BVI max r = 0.830). The mean difference [± standard deviation (SD)] was an underestimation of BV for both BVI mean and BVI max (44.8 ± 88.2 ml and 32.9 ± 87.5 ml, respectively)., Conclusion:: This is the largest study to date (n = 190), assessing the accuracy of the BladderScan® BVI 6100 in the prostate RT population. The BVI 6100 provides an acceptable indication of BV for use in prostate RT patients for the purposes of monitoring BV., Advances in Knowledge:: The BladderScan® BVI 6100 provides a convenient and non-irradiating method of indicating BV for use in prostate RT patients.

Title: Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer. NCT01176487., Background & Purpose: Trials of radiation therapy for the palliation of intra-thoracic symptoms from locally advanced non-small cell lung cancer (NSCLC) have concentrated on optimising fractionation and dose schedules. In these trials, the rates of oesophagitis induced by this "palliative" therapy have been unacceptably high. In contrast, this non-randomised, single-arm trial was designed to assess if more technically advanced treatment techniques would result in equivalent symptom relief and reduce the side-effect of symptomatic oesophagitis., Materials & Methods: Thirty-five evaluable patients with symptomatic locally advanced or metastatic NSCLC were treated using a three-dimensional conformal technique (3-DCRT) and standardised dose regimens of 39 Gy in 13 fractions, 20 Gy in 5 fractions or 17 Gy in 2 fractions. Treatment plans sought to minimise oesophageal dose. Oesophagitis was recorded during treatment, at two weeks, one month and three months following radiation therapy and 3-6 monthly thereafter. Mean dose to the irradiated oesophagus was calculated for all treatment plans., Results: Five patients (14%) had experienced grade 2 oesophagitis or dysphagia or both during treatment and 2 other patients had these side effects at the 2-week follow-up. At follow-up of one month after therapy, there was no grade two or higher oesophagitis or dysphagia reported. 22 patients were eligible for assessment of late toxicity. Five of these patients reported oesophagitis or dysphagia (one had grade 3 dysphagia, two had grade 2 oesophagitis, one of whom also had grade 2 dysphagia). Quality of Life (QoL) data at baseline and at 1-month follow up were available for 20 patients. At 1-month post radiation therapy, these patients had slightly less trouble taking a short walk, less shortness of breath, did not feel as weak, had better appetite and generally had a better overall quality of life than they did at baseline. They did report being slightly more tired., Conclusions: This trial is the first of its kind showing that 3-DCRT provides patients with lower rates of oesophageal toxicity whilst yielding acceptable rates of symptom control. (Sponsored by Cancer Trials Ireland (ICORG) Study number 06-34, the Friends of St. Luke's and the St. Luke's Institute of Cancer Research.)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Treatment outcomes in locally advanced non-small cell lung cancer (NSCLC) to date have been poor, with normal tissue toxicity often limiting the dose that can be delivered to the tumor. Treatment intensification in NSCLC via targeted dose escalation with modern delivery techniques may offer the potential for a significant increase in tumor control probability (TCP) without a clinically significant increase in organ-at-risk (OAR) toxicity. In this planning study, 20 patients were re-planned with a volumetric modulated arc therapy (VMAT) and an inhomogeneous dose distribution with iteratively escalated doses to the gross tumor volume (iGTV) (composite GTV across multiple 4-dimensional computed tomography [4DCT] phases) in a series of 20 fraction regimes. For each plan OAR doses, target coverage and predicted TCPs were collected and compared with homogenous 3-dimensional (3D) and VMAT plans, as well as with each other. In 70% of patients, it was possible to escalate to 75 Gy in 20 fractions within OAR tolerances, opening the possibility of treating these patients to a biological effective dose (BED) of 103.1 Gy 10 . This planning study forms the basis of a clinical trial INTENSE (Inhomogeneous Targeted Dose Escalation in Non-Small CEll Lung Cancer), CTRIAL 15-47., (Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Aims: The objective of this phase II clinical trial was to prospectively evaluate the safety and efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy (3DCRT) in localised non-resectable/non-operable non-small cell lung cancer (NSCLC)., Materials and Methods: Sixty patients with stage I-III NSCLC were enrolled in a prospective single-arm All Ireland Co-operative Oncology Research Group (ICORG 99-09) toxicity end point phase II trial. The protocol allocated patients between three radiation schedule dose levels (60, 66 or 72 Gy, in 20, 22 and 24 fractions, respectively, 3 Gy daily, five fractions per week) according to combined lung V 25Gy (V 25Gy  ≤ 30%) with built-in early stopping toxicity rules. The primary end point was toxicity with evaluation of dose-limiting toxicity. The secondary objectives included radiological tumour response rate at 3 months after the completion of radiation therapy and the thoracic progression-free survival time., Results: Sixty patients were recruited from August 1999 to June 2009. Forty-nine patients were included in the primary per-protocol analysis. Eleven patients were not evaluable. In the first 30 evaluable patient cohort, severe oesophageal toxicity was reported in two patients (2/49; 4% experiencing grade 5 oesophageal late toxicity, related to the 97% oesophageal length). The trial was temporarily closed and was then reopened to validate an oesophageal dose volume constraint (DVC) of limiting the length of oesophagus fully encompassed by the 97% isodose to less than 1 cm (applied to 21 patients). The trial prospectively showed the safety of the oesophageal DVC, with no oesophageal toxicity above grade 3 thereafter. Thirty-nine per cent of patients had disease progression at 3-4 months after radiotherapy, 22% had stable disease, 20% had a complete response and 14% had a partial response. The median overall survival was 13.6 months (95% confidence interval 10.5-16.7) and overall survival at 1 and 3 years was 57% and 29%, respectively., Conclusion: A strategy using accelerated hypofractionated 3DCRT is feasible and reasonably safe for patients with inoperable NSCLC. It is safe to deliver for centrally located tumours if DVCs are applied to the oesophagus, which is the primary dose-limiting toxicity. Further studies are required to assess the efficacy of hypofractionated regimens for centrally located tumours using an oesophageal DVC and monitoring for oesophageal toxicity., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Despite increasing use of robotic surgery for rectal cancer, few series have been published from the practice of generalizable US surgeons., Methods: A retrospective chart review was performed for 71 consecutive patients who underwent robotic low anterior resection (LAR) or abdominoperineal resection (APR) for rectal adenocarcinoma between 2010 and 2014., Results: 46 LARs (65%) and 25 APRs (35%) were identified. Median procedure time was 219 minutes (IQR 184-275) and mean blood loss 164.9 cc (SD 155.9 cc). Radial margin was negative in 70/71 (99%) patients. Total mesorectal excision integrity was complete/near complete in 38/39 (97%) of graded specimens. A mean of 16.8 (SD+/- 8.9) lymph nodes were retrieved. At median follow-up of 21.9 months, there were no local recurrences., Conclusions: Robotic proctectomy for rectal cancer was introduced into typical colorectal surgery practice by a single surgeon, with a low conversion rate, low complication rate, and satisfactory oncologic outcomes., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: We aim to assess the patient factors and concomitant infectious outcomes associated with urinary tract infection (UTI) occurrence and the impact of UTI on length of stay (LOS), re-admission, and death in a colorectal surgical population., Patients and Methods: National Surgical Quality Improvement Program User Data for right colectomy and abdominal perineal resection (APR) procedures for cancer between 2006 and 2012 were analyzed. Concomitant infectious complications and timing of UTI diagnosis, inpatient versus outpatient, were considered., Results: We identified 7,615 right colectomies with 107 (1.4%) UTIs and 2,493 APRs with 88 (3.5%) UTIs (p < 0.001). On multivariable analysis and correction for other post-operative complications, UTI remained statistically correlated with prolonged LOS for right colectomy and APR (LOS increases of 59.0% and 37.4%, respectively, p < 0.001) but not death. Patients with a diagnosis of UTI after discharge showed significantly increased re-admission rates compared with UTI diagnosis before discharge (37.7% vs. 9.7%, p < 0.001)., Conclusions: After excluding deaths, outpatient UTI occurrences, and correcting for other infectious complications, UTI is associated with increased LOS but is not correlated with re-admission or death. Outpatient occurrence of UTI after hospital discharge is associated with a dramatic re-admission rate of 37.7%.

Cancer incidence across Europe is projected to rise rapidly over the next decade. This rising cancer incidence is mirrored by increasing use of and indications for stereotactic radiation. This paper seeks to summarize the exponential increase in indications for stereotactic radiotherapy as well as the evolving economic advantages of stereotactic radiosurgery and stereotactic body radiotherapy.

Background: Patient demographics and outcomes may influence patient satisfaction. We aim to investigate the relationship between postoperative complications and survey-based satisfaction in the context of payer status., Methods: Institutional data were used to identify major complication occurrence and linked to patient satisfaction surveys. The impact of complication occurrence on satisfaction was investigated and stratified by payer status., Results: In all, 1,597 encounters were identified with an 18% major complication rate. Satisfaction scores in specific domains were significantly more likely to be above the median for patients without complications (P < .01) and for payer status Medicaid/low income (P < .05). In sensitivity analyses, we found no significant interactions among payer status, complications, and satisfaction scores., Conclusions: Significant differences exist for individual satisfaction survey domains between patients with and without major postoperative complications and by payer status. Payer status was not found to have an impact on the intersection of major complications and patient satisfaction., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The feasibility, safety, and costs of single-incision robotic colectomy (SIRC) are not known., Methods: A retrospective review was conducted, comparing the initial 29 consecutive SIRC procedures performed to 36 multiport laparoscopic colectomies (MLC)., Results: The groups did not differ significantly on age, body mass index, gender, ASA classification, smoking status, steroid usage or rate of diabetes. Procedure time, conversion rate, infectious complications and length of stay did not differ significantly. The ratio of observed:expected direct hospital costs statistically favoured MLC, although there was no statistical difference between groups for contribution margin, or for observed and expected direct hospital costs., Conclusions: These results demonstrate safety and technical feasibility for SIRC in selected patients with short-term outcomes and hospital costs comparable to MLC. Contribution margin remained positive and expected costs exceeded observed for SIRC. Increased costs for SIRC are a concern. The comparable but relatively high mortality in both groups may represent an institutional approach to colectomy where significant comorbidity is not a contraindication to minimally invasive surgery. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Hypofractionated radiation therapy (RT) regimes in non-small cell lung cancer (NSCLC) have become increasingly popular with a number of international trials currently underway. The majority of the dose-volume-constraints (DVCs) published in the literature refer to conventional 2Gy per fraction deliveries. Here relevant organs-at-risk (OARs) are identified and available dose-volume constraint data discussed and summarised for moderately hypofractionated NSCLC regimes. The OARs examined include lung, brachial plexus, heart, oesophagus, airway and spinal cord. Where available the toxicity rates are also reported with all data summarised tabulated to aid its use in the clinic., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Neoadjuvant "long-course" chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent., Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed., Results: Pelvic external beam radiotherapy (RT) 45-50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2-6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal., Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45-50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort., Advances in Knowledge: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients.

Background: To assess the temporal patterns of late gastrointestinal (GI) and genitourinary (GU) radiotherapy toxicity and resolution rates in a randomised controlled trial (All-Ireland Cooperative Oncology Research Group 97-01) assessing duration of neo-adjuvant (NA) hormone therapy for localised prostate cancer., Material and Methods: Node negative patients with > 1 of: PSA > 20 ng/mL, Gleason score ≥ 7, and stage T3 or more, were included. Follow-up, including toxicity assessment, was three-monthly in the early stages and yearly thereafter., Results: Median follow-up from the end of RT was 6.8 years. In the interval between 90 days following the end of RT and the last toxicity assessment, GI and GU toxicity (any grade) was found in 50% and 51% of 240 and 241 patients, respectively. For those who did develop toxicity, the median time from end of RT until the first development of any grade GI or GU toxicity was 1.2 years and 1.6 years, respectively, whilst median time to final resolution was 1.6 years and 2.2 years, respectively. Grade 2 (G2) or greater GI and GU toxicity occurred in 29 (12.1%) and 40 (16.6%) patients, respectively. The proportion with unresolved G2 + GI and GU toxicity was 89% and 79%, respectively, in year 1, 69% and 65% in year 2, 59% and 52% in year 3 and 27% and 32% in year 5., Conclusion: Long-term toxicities continue to occur many years after NA hormone therapy and RT. The rate of occurrence does not appear to reduce within the time frame during which our patients were followed. The percentage of patients suffering from G2 + toxicity at any time is however low. Resolution of these toxicities continues for the duration of the follow-up.

Purpose: Organ motion is a contributory factor to the variation in location of the prostate and organs at risk during a course of fractionated prostate radiation therapy (RT). A prospective randomized controlled trial was designed with the primary endpoint to provide evidence-based bladder-filling instructions to achieve a consistent bladder volume (BV) and thus reduce the bladder-related organ motion. The secondary endpoints were to assess the incidence of acute and late genitourinary (GU) and gastrointestinal (GI) toxicity for patients and patients' satisfaction with the bladder-filling instructions., Methods and Materials: One hundred ten patients were randomly assigned to 1 of 2 bladder-filling protocols; 540 mL (3 cups) of water or 1080 mL (6 cups) of water, in a single institution trial. A portable ultrasound device, BladderScan BVI 6400 (Verathon Inc, Bothell, WA), measured BVs at treatment planning computed tomography (TPCT) scan and 3 times per week during RT. Maximum bladder dose and BV receiving ≥ 50, 60, and 70 Gy were recorded. Acute and late GU and GI toxicity were evaluated, as were patients' comfort, perception of urinary symptoms, and quality of life (QoL)., Results: There was significantly less BV variation in the 540 mL arm when compared with 1080 mL (median: 76 mL vs 105 mL, P = .003). Larger BVs on initial TPCT correlated with larger BV variations during RT (P < .0005). There were no statistically significant associations between arm and GU/GI toxicity, dose median comfort scores, or median QoL scores., Conclusions: The 540 mL bladder-filling arm resulted in reproducible BVs throughout a course of RT, without any deterioration in QoL or increase in toxicities for prostate patients., (Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Stereotactic radiosurgery is frequently used for the treatment of brain metastases. This study provides a retrospective evaluation of patients with secondary lesions of the brain treated with stereotactic radiosurgery (SRS) at our institution., Aims: To provide outcome data from a single institutional experience with SRS and identify any significant prognostic factors in the cohort., Methods: Sixty-seven patients received first time SRS to 86 intracranial metastases between 2007 and 2010. Sixteen patients were excluded from this study due to the absence of post-treatment neuroimaging, resulting in 51 patients with 64 treated lesions. Of these patients, 37 (72.5%) received SRS electively, while 14 (27.5%) received salvage SRS after brain metastasis progression following whole brain radiotherapy., Results: Median survival for the entire group was 15 months from the date of radiosurgery. Patients without active extracranial disease had statistically significant survival time than those with active extracranial disease (P=0.03). 45 (70.3%) lesions achieved local tumour control in 34 patients (66.7%) with a mean follow-up period of 10.7 months (range 1.7-33.6 months, 95 % confidence interval 6.6-9.8 months)., Conclusions: The results reported in this study equate to those reported in other series consolidating SRS as an effective treatment option with few serious complications. Developments in systemic disease control will see further improvements in overall survival.

Purpose: Although well described, there is limited published data related to management on the coexistence of prostate and rectal cancer. The aim of this study was to describe a single institution's experience with this and propose a treatment algorithm based on the best available evidence., Methods: From 2000 to 2011, a retrospective review of institutional databases was performed to identify patients with synchronous prostate and rectal cancers where the rectal cancer lay in the lower two thirds of the rectum. Operative and non-operative outcomes were analysed and a management algorithm is proposed., Results: Twelve patients with prostate and rectal cancer were identified. Three were metachronous diagnoses (>3-month time interval) and nine were synchronous diagnoses. In the synchronous group, four had metastatic disease at presentation and were treated symptomatically, while five were treated with curative intent. Treatment included pelvic radiotherapy (74 Gy) followed by pelvic exenteration (three) and watchful waiting for rectal cancer (one). The remaining patient had a prostatectomy, long-course chemoradiotherapy and anterior resection. There were no operative mortalities and acceptable morbidity. Three remain alive with two patients disease-free., Conclusions: Synchronous detection of prostate cancer and cancer of the lower two thirds of the rectum is uncommon, but likely to increase with rigorous preoperative staging of rectal cancer and increased awareness of the potential for synchronous disease. Treatment must be individualized based on the stage of the individual cancers taking into account the options for both cancers including EBRT (both), surgery (both), hormonal therapy (prostate), surgery (both) and watchful waiting (both).

Background and Purpose: Erectile dysfunction is a common consequence of external beam radiotherapy (EBRT) for prostate cancer. The addition of neo-adjuvant androgen deprivation (NAD) has an indeterminate additive effect. We examined the long-term effect on erectile function (EF) of two durations (4 months: arm 1 and 8 months: arm 2) of NAD prior to radiation (RT) for patients with localised prostate cancer from the Irish Clinical Oncology Research Group (ICORG 97-01) 4- versus 8-month trial. In this study we aimed to (1) analyse the overall effect on EF of NAD in an EBRT population, (2) compare the probability of retained EF over time in an EBRT population treated with either 4 or 8 months of NAD and (3) identify any variables such as risk group and age which may have an additive detrimental effect. This analysis provides unique long term follow up data., Materials and Methods: From 1997 to 2001, 276 patients with adenocarcinoma of the prostate were randomised to 4 or 8 months of NAD before RT. EF data were recorded at baseline and at each follow-up visit by physician directed questions, using a 4-point grading system., Results: Two hundred and thirty patients were included in the analysis of EF and were followed for a median of 80 months. One hundred and forty-one patients had EF at baseline. Neo-adjuvant androgen deprivation in addition to radiation therapy caused a significant reduction in EF. The most significant reduction in EF happens within the first year. The median time to grade 3-4 EF toxicity was 14.6 months, 17.6 months in arm 1 and 13.7 in arm 2. Freedom from late EF toxicity did not differ significantly between arms, overall or at 5 years (n=141). The cumulative probability of EF preservation at 5 years was 28% (22-34) in arm 1 and 24% (19-30) in arm 2. Age was a significant predictor of post-treatment EF., Conclusions: The first year post ADT and EBRT poses the greatest risk to sexual function and a continued decline may be expected. However, 26% of men can expect to retain sexual function at 5 years., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer-specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories., Patients and Methods: Between February 2, 1996, and December 27, 2001, 761 men with unfavorable-risk PC were treated in Australia, New Zealand, Ireland, or the United States in a randomized trial with radiotherapy and 3, 4, or 6 months of AST (the study cohort). Competing risks regression was used to evaluate whether the duration of AST interacted with GS and was significantly associated with the risk of PCSM, adjusting for age, trial site, and PC prognostic factors., Results: After a median follow-up of 10.9 years, 263 men died, 111 (42%) from PC. For all men, 6 versus 3 or 4 months of AST was associated with a reduced risk of PCSM (adjusted hazard ratio [AHR], 0.55; 95% CI, 0.36 to 0.82; P = .004). AHRs evaluating the impact of the duration of AST on the risk of PCSM were 0.67 (95% CI, 0.29 to 1.56; P = .35), 0.47 (95% CI, 0.25 to 0.85; P = .01), and 0.59 (95% CI, 0.30 to 1.19; P = .14) for men with GS ≤ 6, 7, and 8 to 10 PC, respectively. Therefore, the strongest evidence for this benefit was in men with GS 7 PC., Conclusion: AST durations of no less than 6 months should be considered when treating GS 7 PC with conventional dose RT.

Purpose: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer., Methods and Materials: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng/mL, Gleason score≥7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival., Results: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2., Conclusion: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To determine the rate of prescription of and government expenditure for domiciliary oxygen therapy (DOT) in Australia, and to identify interstate differences in rates, costs and service provision., Design: Retrospective observational study., Participants and Setting: Government departments and health services (state and federal) that funded DOT in Australia in the 2004-05 financial year (including the Department of Veterans' Affairs [DVA] and the Department of Health and Ageing [DoHA])., Main Outcome Measures: Prescription rates, cost of DOT in 2004-05, and services provided in each jurisdiction., Results: In 2005, 20,127 patients were using DOT, giving a national prevalence of 100 prescriptions per 100,000 population. The total cost was about $31 million. State governments, the DVA and the DoHA funded 13,899 (69%), 4084 (20%) and 2144 (11%) patients, respectively. Prescription rates varied threefold between the states, ranging from 44 (Northern Territory) to 133 (Tasmania) per 100,000 population. Cost per patient per year varied fourfold between the DVA and the DoHA. All jurisdictions funded oxygen according to the clinical criteria of the Thoracic Society of Australia and New Zealand, but considerable variability in service provision was identified., Conclusion: DOT prescription rates and costs vary considerably between jurisdictions. An urgently needed national DOT register would enable the current variability to be understood and allow service planning and benchmarking of clinical outcomes.

We report the case of a 41-year-old mentally retarded male with recurrent pilomatrix carcinoma of the occipital region which invaded the occipital bone, left cerebellum and left temporal lobe. At his initial presentation the patient had a craniotomy and subtotal excision of the lesion with positive margins. He received no adjuvant therapy. After an early intracranial recurrence he had subtotal debulking and was referred for external beam radiotherapy. At 27 months follow-up after adjuvant external beam radiotherapy the intracranial component has not progressed and the patient remains clinically well.

Pilomatrix carcinoma is the rare malignant counterpart of pilomatrixoma, a skin adnexal tumour originating from hair matrix cells. Pilomatrix carcinoma can arise as a solitary lesion de novo, or through transformation of a pilomatrixoma. Pilomatrixoma was first described erroneously as being of sebaceous gland origin but was later discovered to be derived from hair matrix cells. They are rare, slow growing tumours of the skin found in the lower dermis and subcutaneous fat and are predominantly found in the neck and the scalp. While known to be locally aggressive, no malignant form was thought to exist until it was described relatively recently. Since then, approximately ninety cases of pilomatrix carcinoma have been reported.We report the case of a 41 year old mentally retarded male who had a longstanding lesion in the left neck for approximately fifteen years previously diagnosed as a pilomatrixoma. He presented with severe headache, falls and visual disturbance and a biopsy showed pilomatrix carcinoma of the occipital region which, on computed tomography ( CT ) invaded the occipital bone, the cerebellum and the left temporal lobe. At his initial presentation he had a craniotomy and subtotal excision of the lesion but received no adjuvant therapy. After an early intracranial recurrence he had further debulking and adjuvant external beam radiotherapy. He has had no further intracranial recurrence after three and a half years of follow-up. Here we present the pathological features of this uncommon tumour.

Background: Existing severity assessment tools, such as the pneumonia severity index (PSI) and CURB-65 (tool based on confusion, urea level, respiratory rate, blood pressure, and age >or=65 years), predict 30-day mortality in community-acquired pneumonia (CAP) and have limited ability to predict which patients will require intensive respiratory or vasopressor support (IRVS)., Methods: The Australian CAP Study (ACAPS) was a prospective study of 882 episodes in which each patient had a detailed assessment of severity features, etiology, and treatment outcomes. Multivariate logistic regression was performed to identify features at initial assessment that were associated with receipt of IRVS. These results were converted into a simple points-based severity tool that was validated in 5 external databases, totaling 7464 patients., Results: In ACAPS, 10.3% of patients received IRVS, and the 30-day mortality rate was 5.7%. The features statistically significantly associated with receipt of IRVS were low systolic blood pressure (2 points), multilobar chest radiography involvement (1 point), low albumin level (1 point), high respiratory rate (1 point), tachycardia (1 point), confusion (1 point), poor oxygenation (2 points), and low arterial pH (2 points): SMART-COP. A SMART-COP score of >or=3 points identified 92% of patients who received IRVS, including 84% of patients who did not need immediate admission to the intensive care unit. Accuracy was also high in the 5 validation databases. Sensitivities of PSI and CURB-65 for identifying the need for IRVS were 74% and 39%, respectively., Conclusions: SMART-COP is a simple, practical clinical tool for accurately predicting the need for IRVS that is likely to assist clinicians in determining CAP severity.

Background: We report the case of a patient with treated Stage Ia seminoma who was found to have an elevated beta human chorionic gonadotrophin (hCG) on routine follow - up. This instigated restaging and could have lead to commencement of chemotherapy., Case Presentation: The patient was a bodybuilder, and following a negative metastatic work - up, admitted to injecting exogenous beta hCG. This was done to reduce withdrawal symptoms from androgen abuse. The patient remains well eight years post diagnosis., Conclusion: This case highlights the need for surgical oncologists to conduct vigilant screening of young male patients with a history of testicular germ cell tumours and who may indulge in steroid abuse.

Background: Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide., Methods: The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded., Results: The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified., Conclusions: The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

Enkephalins are opioid peptides that are found at high levels in the brain and endocrine tissues. Studies have shown that enkephalins play an important role in behavior, pain, cardiac function, cellular growth, immunity, and ischemic tolerance. Our global hypothesis is that enkephalins are released from non-neuronal tissues in response to brief ischemia or exercise, and that this release contributes to cardioprotection. To identify tissues that could serve as potential sources of enkephalins, we used real-time PCR, Western blot analysis, ELISA, immunofluorescence microscopy, and ex vivo models of enkephalin release. We found widespread expression of preproenkephalin (pPENK) mRNA and production of the enkephalin precursor protein proenkephalin (PENK) in rat and mouse tissues, as well as in tissues and cells from humans and pigs. Immunofluorescence microscopy with anti-enkephalin antisera demonstrated immunoreactivity in rat tissues, including heart and skeletal muscle myocytes, intestinal and kidney epithelium, and intestinal smooth muscle cells. Finally, isolated tissue studies showed that heart, skeletal muscle, and intestine released enkephalins ex vivo. Together our studies indicate that multiple non-neuronal tissues produce PENK and release enkephalins. These data support the hypothesis that non-neuronal tissues could play a role in both local and systemic enkephalin-mediated effects.

Background: Weekly symptoms of gastroesophageal reflux disease (GERD) occur in 20% of the population, and GERD has been implicated in the pathophysiology of many respiratory diseases. Microaspiration of contaminated water is a potential portal of entry for Mycobacterium avium complex (MAC) organisms into the respiratory tract, and acid-suppression therapy may enhance the survival of mycobacteria in the stomach. This study aimed to assess the prevalence of GERD, swallowing disorders, reflux symptoms, and acid-suppression therapy in patients with MAC lung disease (MAC positive [MAC+]), and to compare these patients to control subjects without MAC lung disease (MAC negative [MAC-])., Methods: Clinical information was collected on 58 MAC+ patients and 58 age- and sex-matched MAC- patients who were asked to complete a DeMeester questionnaire of reflux symptoms and to identify any acid-suppressive medication consumed., Results: A clinical diagnosis of GERD was documented in 23 of 52 MAC+ patients (44.2%), compared to 16 MAC- patients (27.6%) [p = 0.019]. MAC+ patients consumed significantly more histamine type 2 receptor antagonists and prokinetic agents, and MAC- patients consumed more antacids. The mean DeMeester questionnaire score (+/- SD) for MAC+ patients was 1.39 +/- 1.8, and for MAC- patients was 0.88 +/- 1.4. (p = 0.098). Aspiration was suspected in nine MAC+ patients (15.5%), compared to three MAC- patients (5.2%) [p = 0.032]. There was no association between GERD and radiologic presentation of MAC disease. Consolidation and nodules > 5 mm were more common in those receiving acid suppression than those who were not., Conclusions: GERD, acid suppression, and clinically suspected aspiration are more common in patients with MAC lung disease than in similar patients without MAC disease.

Anti-glomerular basement membrane (anti-GBM) disease represents the spectrum of disease attributable to circulating anti-GBM antibodies. While active anti-GBM disease in the absence of circulating anti-GBM antibodies has been described, it is considered rare with the use of current routinely available assays. We report four subjects with features consistent with active anti-GBM antibody disease without detectable antibodies by routinely available enzyme linked immunosorbent assay (ELISA) and immunoblot techniques. All were smokers who presented with diffuse alveolar haemorrhage, minimal renal involvement, and undetectable anti-GBM antibodies. Seronegative anti-GBM disease with predominant pulmonary involvement may be more common than previously appreciated and should be part of the differential diagnosis for otherwise unexplained diffuse alveolar haemorrhage. Renal biopsy with immunofluorescent studies should be considered in the diagnostic evaluation of such subjects, including those with idiopathic pulmonary haemosiderosis.

We report on a strain of Mycobacterium tuberculosis with a deletion in the protein antigen B gene overlapping the probe binding sites for the Abbott Diagnostics LCx M. tuberculosis (LCx-MTB) probe assay. A false-negative result with the LCx-MTB assay delayed a laboratory diagnosis of tuberculosis.

Aim: The feasibility and improved efficacy of six conventional fractions per week has previously been proven in a Danish randomized trial. We tested the tolerance and efficacy of seven conventional fractions per week using a concomitant boost technique., Methods: From September 1996 to May 1998, 20 patients with squamous cancer of the head and neck were treated with radiation alone. The site of disease was oropharynx in 35%, larynx in 30%, oral cavity 20%, and hypopharynx in 15%. All patients had stage III (10%)/IV (90%) disease. The planned total dose to gross disease was 66 Gy delivered in 33 fractions of 2 Gy each in 31 days. Large volumes were treated to 46 Gy, 2 Gy per fraction, once each morning, Monday-Friday. Boosts to gross disease consisted of 20 Gy in 10 fractions > or = 6 h after the morning dose on Tuesday and Thursday., Results: Acute toxicity > or = grade 3 was mucous membrane 75%, pharynx 60%, skin 65%, and larynx 35%. One acute toxicity was fatal. Chronic toxicity > or = grade 3 (three patients) was mucous membrane 5%, pharynx 10%, skin 5%, salivary 15%, and larynx 5%. All patients with grade III or greater late toxicity had grade III acute toxicity in each toxicity category. At 30 months Kaplan-Meier survival is 55%, and local control is 39%., Conclusions: Without increasing resource utilization this scheme accelerates treatment by 30%. As expected acute toxicity is high but manageable. Chronic toxicity appears comparable to other altered fractionation strategies however the median follow up is only 30 months more toxicity may emerge as the data matures. We plan further trials using 1.8 Gy fractions to reduce toxicity.

We performed this analysis to document the rate and severity of complications both during and after local field irradiation for localized prostate cancer and to assess the influence of three-dimensional conformal radiation therapy (3DCRT) on these complications. Bowel, urinary and cutaneous toxicities were noted in all patients treated with primary radiotherapy (RT) for prostate cancer using Radiation Therapy Oncology Group/European Organization for Research on Treatment of Cancer scores. Evaluations were performed weekly during RT, 6 weeks after RT and 3 monthly thereafter. Data on 111 were analysed. We also compared the complications of conventional and 3DCRT. The serious complication rates identified in this study compare favourably with those reported in the literature. Only 3.6%, 0.8% and 0% had acute grade 3 or 4 urinary, bowel or skin reactions respectively. Only two patients had chronic grade 3 or 4 urinary complications. Thus far no patients have developed chronic bowel or skin complications greater than grade 2. Despite dose escalation from 66 Gy to 70 Gy (with 3DCRT), there was a trend towards reduced toxicity when 3DCRT was compared with conventional radiation. RT is a well-tolerated treatment for early stage carcinoma of the prostate and our complication rates are compatible with international experiences. Further follow-up is required to determine the efficacy of treatment, the incidence of impotence and the final number of late complications.