Bacteriology and clinical outcomes of patients with culture-positive pleural infection in Western Australia: A 6-year analysis.

BACKGROUND AND OBJECTIVE: Pleural infection is a clinical challenge; its microbiology can be complex. Epidemiological and outcome data of pleural infection in adult Australians are lacking. We describe the bacteriology and clinical outcomes of Australian adults with culture-positive pleural infection (CPPI) over a 6-year period. METHODS: Cases with CPPI were identified through Western Australian public hospitals electronic record. Culture isolates, admission dates, vital status, co-morbidities, radiology, blood and pleural fluid tests were extracted. RESULTS: In total, 601 cases (71.4% males; median age: 63 years (IQR: 50-74); median hospital stay 13 days) involving 894 bacterial isolates were identified. Hospital-acquired (HA)-CPPI was defined in 398 (66.2%) cases, community-acquired (CA)-CPPI in 164 (27.3%) cases and the remaining classified as oesophageal rupture/leak. Co-morbidities, most frequently cancer, were common (65.2%). Radiological evidence of pneumonia was present in only 43.8% of CA-CPPI and 27.3% of HA-CPPI. Of the 153 different bacterial strains cultured, Streptococcus species (32.9%) especially viridans streptococci group were most common in CA-CPPI, whereas HA-CPPI was most often associated with Staphylococcus aureus (11.6%) and Gram-negative (31.9%) infections. Mortality was high during hospitalization (CA-CPPI 13.4% vs HA-CPPI 16.6%; P = 0.417) and at 1 year (CA-CPPI 32.4% vs HA-CPPI 45.5%; P = 0.006). CONCLUSION: This is the first large multicentre epidemiological study of pleural infection in Australian adults and includes the largest cohort of HA-CPPI published to date. CPPI is caused by a diverse range of organisms which vary between CA and HA sources. CPPI is a poor prognostic indicator both in the short term and in the subsequent 12 months.

Streptococcus pneumoniae potently induces cell death in mesothelial cells.

Pleural infection/empyema is common and its incidence continues to rise. Streptococcus pneumoniae is the commonest bacterial cause of empyema in children and among the commonest in adults. The mesothelium represents the first line of defense against invading microorganisms, but mesothelial cell responses to common empyema pathogens, including S. pneumoniae, have seldom been studied. We assessed mesothelial cell viability in vitro following exposure to common empyema pathogens. Clinical isolates of S. pneumoniae from 25 patients with invasive pneumococcal disease and three reference strains were tested. All potently induced death of cultured mesothelial cells (MeT-5A) in a dose- and time-dependent manner (>90% at 107 CFU/mL after 24 hours). No significant mesothelial cell killing was observed when cells were co-cultured with Staphylococcus aureus, Streptococcus sanguinis and Streptococcus milleri group bacteria. S. pneumoniae induced mesothelial cell death via secretory product(s) as cytotoxicity could be: i) reproduced using conditioned media derived from S. pneumoniae and ii) in transwell studies when the bacteria and mesothelial cells were separated. No excess cell death was seen when heat-killed S. pneumoniae were used. Pneumolysin, a cytolytic S. pneumoniae toxin, induced cell death in a time- and dose-dependent manner. S. pneumoniae lacking the pneumolysin gene (D39 ΔPLY strain) failed to kill mesothelial cells compared to wild type (D39) controls, confirming the necessity of pneumolysin in D39-induced mesothelial cell death. However, pneumolysin gene mutation in other S. pneumoniae strains (TIGR4, ST3 and ST23F) only partly abolished their cytotoxic effects, suggesting different strains may induce cell death via different mechanisms.

Human pleural fluid is a potent growth medium for Streptococcus pneumoniae.

Empyema is defined by the presence of bacteria and/or pus in pleural effusions. However, the biology of bacteria within human pleural fluid has not been studied. Streptococcus pneumoniae is the most common cause of pediatric and frequent cause of adult empyema. We investigated whether S. pneumoniae can proliferate within human pleural fluid and if growth is affected by the cellular content of the fluid and/or characteristics of pneumococcal surface proteins. Invasive S. pneumoniae isolates (n = 24) and reference strain recovered from human blood or empyema were inoculated (1.5×106CFU/mL) into sterile human malignant pleural fluid samples (n = 11). All S. pneumoniae (n = 25) strains proliferated rapidly, increasing by a median of 3009 (IQR 1063-9846) from baseline at 24hrs in all pleural effusions tested. Proliferation was greater than in commercial pneumococcal culture media and concentrations were maintained for 48hrs without autolysis. A similar magnitude of proliferation was observed in pleural fluid before and after removal of its cellular content, p = 0.728. S. pneumoniae (D39 strain) wild-type, and derivatives (n = 12), each with mutation(s) in a different gene required for full virulence were inoculated into human pleural fluid (n = 8). S. pneumoniae with pneumococcal surface antigen A (ΔpsaA) mutation failed to grow (2207-fold lower than wild-type), p<0.001, however growth was restored with manganese supplementation. Growth of other common respiratory pathogens (n = 14) across pleural fluid samples (n = 7) was variable and inconsistent, with some strains failing to grow. We establish for the first time that pleural fluid is a potent growth medium for S. pneumoniae and proliferation is dependent on the PsaA surface protein and manganese.

Implanted brachytherapy seed movement reflecting transrectal ultrasound probe-induced prostate deformation.

PURPOSE: Compression of the prostate during transrectal ultrasound-guided permanent prostate brachytherapy is not accounted for during treatment planning. Dosimetry effects are expected to be small but have not been reported. The study aims to characterize the seed movement and prostate deformation due to probe pressure and to estimate the effects on dosimetry. METHODS AND MATERIALS: C-arm fluoroscopy imaging was performed to reconstruct the implanted seed distributions (compressed and relaxed prostate) for 10 patients immediately after implantation. The compressed prostate was delineated on ultrasound and registered to the fluoroscopy-derived seed distribution via manual seed localization. Thin-plate spline mapping, generated with implanted seeds as control points, was used to characterize the deformation field and to infer the prostate contour in the absence of probe compression. Differences in TG-43 dosimetry for the compressed prostate and that on probe removal were calculated. RESULTS: Systematic seed movement patterns were observed on probe removal. Elastic decompression was characterized by expansion in the anterior-posterior direction and contraction in the superior-inferior and lateral directions up to 4 mm. Bilateral shearing in the anterior direction was up to 6 mm, resulting in contraction of the 145 Gy prescription isodose line by 2 mm with potential consequences for the posterior-lateral margin. The average whole prostate D90 increased by 2% of prescription dose (6% max; p < 0.01). CONCLUSIONS: The current investigation presents a novel study on ultrasound probe-induced deformation. Seed movements were characterized, and the associated dosimetry effects were nonnegligible, contrary to common expectation.

Pleural empyema caused by Klebsiella oxytoca: a case series.

We report on 19 patients from Western Australia of pleural empyema with Klebsiella oxytoca, an organism never before reported in association with this condition. Median age was 65 years, 14/17 (83%) had been in hospital within 30 days prior to diagnosis, 12/18 (67%) had active cancer, 9/17 (53%) had been in intensive care and 7/17 (41%) had prior surgery. Nine patients died at the time of censure, five within 90 days of infection.

A comparison of phase, amplitude, and velocity binning for cone-beam computed tomographic projection-based motion reconstruction.

PURPOSE: We previously developed a motion estimation technique based on direct cone-beam projection analysis. It is able to reconstruct the complete motion trajectory of a radio-opaque marker, including cycle-to-cycle variability, using respiratory binning of the projection images. This paper investigates the use of phase, amplitude, and amplitude-velocity binning in the context of projection-based cone-beam motion estimation (CBME). METHODS AND MATERIALS: We simulated cone-beam computed tomographic scans of 160 tumor trajectories estimated by a CyberKnife Synchrony System (Accuray, Sunnyvale, CA), and reconstructed the complete trajectory with CBME using phase, amplitude, and amplitude-velocity binning of the projection data. Various numbers of respiratory bins, from 1 (no binning) to 100, were used for phase and amplitude binning, while 1 to 100 amplitude bins with 4 velocity bins were used for amplitude-velocity binning. From this large pool of data, we correlated the reconstruction accuracy with bin type, total number of bins, number of breathing cycles per bin, and the position of the bin within the breathing cycle. RESULTS: CBME predicted the true motion of the marker with a 3-dimensional (3D) mean root mean square (RMS) error of 0.24 mm for amplitude-velocity binning, 0.31 mm for amplitude binning, and 0.52 mm for phase binning. Reconstruction 3D RMS error increased to over 1 mm when less than 3 breathing cycles contributed to a bin. We found that reconstruction accuracy was optimized when about 20 bins were used. Accuracy also decreased in bins located around the inhale portion of the breath cycle, compared with the mid- and end-exhale positions. CONCLUSIONS: This study provides a quantitative assessment of phase, amplitude, and amplitude-velocity binning for CBME. A joint binning approach should be used to give both the accuracy of amplitude binning, as well as the robustness of phase binning, in areas of limited motion sampling.

Brachytherapy for carcinoma of the cervix: a Canadian survey of practice patterns in a changing era.

BACKGROUND AND PURPOSE: This survey aimed to document practices of Canadian radiation oncologists performing gynecologic brachytherapy for carcinoma of the cervix and to determine what the effect of the phasing-out of LDR after-loading systems from the commercial market is having on practice. MATERIALS AND METHODS: A 26-item questionnaire was developed to survey various aspects of brachytherapy practice to include: number of patients treated, prescription points/volume, dose and fractionation, timing, critical structure delineation, expected changes due to the phasing-out of support for low dose rate systems, and support for the development of national guidelines. A link to a web-based survey collection instrument was emailed to each radiation oncologist in Canada practicing gynecologic brachytherapy. RESULTS: A 67% response rate was achieved in this web-based survey. Radiation oncologists currently using HDR brachytherapy are most commonly delivering 5 fractions of 6 Gy in addition to an EBRT dose of 45 Gy in 25 fractions. The median total dose equivalents to Point A was 82.9 Gy for both early and advanced disease. In response to the announcement by a major vendor that they would be phasing-out service for a popular LDR after-loader, 49% of Canadian radiation oncologists who practice brachytherapy for cervix cancer are changing to an HDR technique with a further 9% changing to a PDR technique. Eighty-six percent of respondents would support the development of national guidelines for cervix brachytherapy in Canada. CONCLUSIONS: Variation in practice exists in Canada in brachytherapy for cervix cancer. Many centers are in the process of phasing-out LDR techniques in response to the withdrawal of commercial support for these systems. Support for the development of Canadian national guidelines is high.

Evaluation of linear accelerator performance standards using an outcome oriented approach.

Radiation therapy, along with other branches of medicine, is moving towards a firmer basis in evidence to optimally utilize resources. As new treatment technology and strategies place greater demands on quality assurance resources, the need to objectively evaluate equipment and process performance standards from the perspective of predicted clinical impact becomes more urgent. This study evaluates the appropriateness of recommended quality control tolerance and action levels for linear accelerators based on the calculated dosimetric impact of suboptimal equipment performance. A method is described to quantify the dosimetric changes, as reflected by the changes in the outcome surrogate, equivalent uniform dose (EUD), of machine performance deviations from the optimal, specifically in the range of tolerance and action levels promulgated by the Canadian Association of Provincial Cancer Agencies (CAPCA). Linear accelerator performance deviations were simulated for the treatment of prostate, breast, lung, and brain using 3D conformal techniques, and the impact evaluated in terms of the changes in the EUD of the target volumes and two principal organs at risk (OARs) per site. The eight key performance characteristics examined are: Output constancy, beam flatness, gantry angle, collimator angle, field size indicator, laser alignment (three directions) and, by inference, the optical distance indicator. Currently accepted CAPCA tolerance levels for these eight performance characteristics are shown to maintain average EUD deviations to within 2% for the targets and 2 Gy for the OARs. However, within the 2% or 2 Gy range, the recommended tolerance levels are found to have markedly different effects on the EUDs of the structures of interest.

Verifying monitor unit calculations for tangential whole breast fields in 3-dimensional planning.

An essential component of quality assurance in radiation therapy is verifying the accuracy of monitor unit calculations. For tangential breast fields, monitor unit differences between primary calculations and second checks are usually larger than considered acceptable at other anatomical sites. A simple model to reconcile the differences between sophisticated and simple algorithms is presented, based on estimating the the volume irradiated by the field, replacing the breast contour with a rectangular block having an equal volume but a new field width which provides almost equivalent scatter to the prescription point. This analysis can also assist the treatment planning physicist in selecting a tolerance window for verifying monitor unit calculations for tangential breast fields.

Variability in patterns of BK viral load after renal transplantation.

BK virus (BKV) may cause nephropathy in renal transplant patients, resulting in graft dysfunction and possible graft loss. We used a sensitive quantitative BKV assay to monitor plasma BK viral loads in 11 renal transplant patients for periods ranging from 37 to 189 weeks posttransplant. Five patients remained negative for BKV, and 6 developed viremia, including 1 patient with a transient viremia. Of the viremic patients, 2 were diagnosed with BKV nephropathy after increasing serial BK viral loads, prompting a renal biopsy that established the diagnosis. A 3rd patient had high initial BK viral load and biopsy-proven disease that resolved with reduced immunosuppression. Two patients did not develop nephropathy despite persistent viral loads of 10(4) copies/mL. Five of 6 patients experienced viral clearance from the plasma (BK viral load <500 copies/mL), which was associated with their renal function becoming stabilized, and the remaining patient experienced a downward trend in viral load and stable renal function. Thus, the BKV quantitative assay was useful in aiding the diagnosis of BKV nephropathy, monitoring the response to reductions in immunosuppression and identified that some patients can have persistent viremia and still develop stable renal function without specific antiviral therapy.

Enhanced efficiency and ergonomics of an intraoperative automated prostate brachytherapy delivery technique.

INTRODUCTION: In 2003, the Tom Baker Cancer Centre started a prostate brachytherapy program using Iodine-125 seeds, intraoperative treatment planning, and an automated remote afterloader, the seedSelectron. Over a 3-month period in 2004-2005, technologic changes were implemented with the intent of reducing the time spent in the operating room and improving ergonomics for the radiation oncologist/surgeon. New commercial software including inverse planning was installed, concurrent needle insertion and seed train building was implemented, and additional hardware (a slave monitor) was connected to the system. PURPOSE: To demonstrate that, with these enhancements, dosimetry is not compromised, whereas efficiency is significantly improved. METHODS: Interactive inverse planning was used to create the treatment plans in the operating room. Seed-spacer trains were built concurrently with each needle's insertion guided by rotating the ultrasound probe to the correct sagittal plane using the Needle Navigator feature. Needles were built, inserted, and delivered one needle at a time. Needle coordinate and insert positions were verified on the live ultrasound image displayed on both the slave monitor positioned above the patient's pelvis and the operator console. Dosimetry parameters (D(90) and V(100)), numbers of seeds, and OR times were compared for 20 patients before and 11 patients after the implementation of the concurrent insertion and build protocol combined with inverse planning and the slave monitor. RESULTS: Operating room (OR) times (probe in to probe out) were reduced by 33 min and the number of seeds per unit volume by 3% on an average. The majority of the decrease in time is due to the concurrent building and insertion of needles. Before and after the new technique, average postplan D(90) and V(100) values at 4 weeks after the implant were the same to within 4 Gy and 0.1%, respectively. The range (max-min) of D(90) decreased by 20% of the mean dose and the V(100) range decreased by 6% with the new technique. Adding the slave monitor improved quality assurance of the delivery process and ergonomics for physicians. CONCLUSIONS: The concurrent insertion and build protocol, together with inverse planning and the slave monitor, have decreased OR times with greater consistency in the delivered dose distribution.

Bypassing the learning curve in permanent seed implants using state-of-the-art technology.

PURPOSE: The aim of this study was to demonstrate, based on clinical postplan dose distributions, that technology can be used efficiently to eliminate the learning curve associated with permanent seed implant planning and delivery. METHODS AND MATERIALS: Dose distributions evaluated 30 days after the implant of the initial 22 consecutive patients treated with permanent seed implants at two institutions were studied. Institution 1 (I1) consisted of a new team, whereas institution 2 (I2) had performed more than 740 preplanned implantations over a 9-year period before the study. Both teams had adopted similar integrated systems based on three-dimensional (3D) transrectal ultrasonography, intraoperative dosimetry, and an automated seed delivery and needle retraction system (FIRST, Nucletron). Procedure time and dose volume histogram parameters such as D90, V100, V150, V200, and others were collected in the operating room and at 30 days postplan. RESULTS: The average target coverage from the intraoperative plan (V100) was 99.4% for I1 and 99.9% for I2. D90, V150, and V200 were 191.4 Gy (196.3 Gy), 75.3% (73.0%), and 37.5% (34.1%) for I1 (I2) respectively. None of these parameters shows a significant difference between institutions. The postplan D90 was 151.2 Gy for I1 and 167.3 Gy for I2, well above the 140 Gy from the Stock et al. analysis, taking into account differences at planning, results in a p value of 0.0676. The procedure time required on average 174.4 min for I1 and 89 min for I2. The time was found to decrease with the increasing number of patients. CONCLUSION: State-of-the-art technology enables a new brachytherapy team to obtain excellent postplan dose distributions, similar to those achieved by an experienced team with proven long-term clinical results. The cost for bypassing the usual dosimetry learning curve is time, with increasing team experience resulting in shorter treatment times.

A comparison of techniques for simulating set-up error and uncertainty in head and neck IMRT.

We have compared four computational methods for quantifying the effect of set-up error and uncertainty on delivered doses to targets and organs at risk in the intensity modulated radiation therapy treatment of head and neck cancer. These four methods were direct simulation, simple convolution, plus two modified convolution approaches. Discrepancies of up to 20% in the equivalent uniform dose (EUD) between direct simulation and simple convolution were estimated for the relatively superficial parotid gland at a systematic set-up error of 6 mm standard deviation and a random uncertainty of 2 mm standard deviation. Truncated convolution agreed with direct simulation to within 6% for all situations studied. However, of the four methods, only direct simulation can quantify the range of outcomes (EUD) associated with a finite number of courses and fractions. Our results are particularly relevant to the design of dose escalation studies in head and neck cancer.

Verifying monitor unit calculations for tangential breast fields.

An essential component of quality assurance in radiation therapy is verifying the accuracy of monitor unit calculations. Differences between between sophisticated algorithms using 2.5D or 3D calculations and simpler Monitor unit check algorithms assuming a flat water phantom must be expected. For many anatomical sites such differences are small and of little or no consequence in the context of monitor unit verification. However, for tangential breast fields the discrepancies are considerably larger than those that would generally be considered acceptable. A simple model to reconcile the differences between sophisticated and simple algorithms is presented based on replacing the breast contour with a triangular or elliptical contour and using this to estimate an equivalent rectangle providing equivalent scatter to the prescription point. The elliptical approximation reconciles the observed differences in calculated monitor units. The analysis we present can assist the treatment planning physicist in selecting a method and tolerance window for verifying monitor unit calculations for tangential breast fields.

A technical evaluation of the Nucletron FIRST system: conformance of a remote afterloading brachytherapy seed implantation system to manufacturer specifications and AAPM Task Group report recommendations.

The Fully Integrated Real-time Seed Treatment (FIRST) system by Nucletron has been available in Europe since November 2001 and is being used more and more in Canada and the United States. Like the conventional transrectal ultrasound implant procedure, the FIRST system utilizes an ultrasound probe, needles, and brachytherapy seeds. However, this system is unique in that it (1) utilizes a low-dose-rate brachytherapy seed remote afterloader (the seedSelectron), (2) utilizes 3D image reconstruction acquired from electromechanically controlled, nonstepping rotation of the ultrasound probe, (3) integrates the control of a remote afterloader with electromechanical control of the ultrasound probe for integrating the clinical procedure into a single system, and (4) automates the transfer of planning information and seed delivery to improve quality assurance and radiation safety. This automated delivery system is specifically intended to address reproducibility and accuracy of seed positioning during implantation. The FIRST computer system includes two software environments: SPOT PRO and seedSelectron; both are used to facilitate treatment planning and brachytherapy seed implantation from beginning to completion of the entire procedure. In addition to these features, the system is reported to meet certain product specifications for seed delivery positioning accuracy and reproducibility, seed calibration accuracy and reliability, and brachytherapy dosimetry calculations. Consequently, a technical evaluation of the FIRST system was performed to determine adherence to manufacturer specifications and to the American Association of Physicists in Medicine (AAPM) Task Group Reports 43, 53, 56, 59, and 64 and recommendations of the American Brachytherapy Society (ABS). The United States Nuclear Regulatory Commission (NRC) has recently added Licensing Guidance for the seedSelectron system under 10 CFR 35.1000. Adherence to licensing guidance is made by referencing applicable AAPM Task Group recommendations. In general, results of this evaluation indicated that the system met its claimed specifications as well as the applicable recommendations outlined in the AAPM and ABS reports.