Chlormethine gel is effective for the treatment of skin lesions in patients with early- and late-stage mycosis fungoides in clinical practice.

BACKGROUND: Chlormethine gel is a skin-directed therapy used for patients with mycosis fungoides (MF) that showed a favourable risk/benefit profile in a randomized clinical trial. Currently, data on chlormethine gel use in real-world settings are limited. OBJECTIVES: The aim of this study was to assess safety and efficacy of chlormethine gel treatment in patients treated during daily clinical practice and investigate associations between response and disease stage, lesion type, mono- or combination therapy, and occurrence of dermatitis. METHODS: Clinical data from patients using chlormethine gel from three sites in Greece were analysed. Efficacy was assessed through modified Severity-Weighted Assessment Tool (mSWAT) scores. Safety assessments included analysis of the occurrence and severity of dermatitis. The Skindex-29 questionnaire was used for quality-of-life assessments. RESULTS: Fifty-eight patients were included. The overall response rate (ORR) increased from 37.9% at month 1 to 80.8% at month 9. For 64.2% of patients, response was maintained for at least 4 months (ORR4). At month 3, a higher ORR was seen for patients with patches (69.7%) than patients with plaques/tumours (both 15.2%). A higher ORR4 was observed for patients with early- vs late-stage disease (71.4% vs. 36.4%) and patients on mono- vs combination therapy (75% vs. 47.6%). Dermatitis was observed in the majority of patients (72.4%), but the presence or severity of dermatitis was not directly correlated with treatment response. Both mSWAT and Skindex-29 scores decreased significantly during treatment, and changes in these scores from baseline to month 6 showed a positive correlation (r = 0.55, P = 0.026). CONCLUSIONS: Chlormethine gel was effective for the treatment of skin lesions in patients with early- and late-stage MF in clinical practice. Response rates increased over time, indicating that continued treatment with the gel is important. Dermatitis may be managed by reducing the treatment frequency; the occurrence of dermatitis did not affect the response to treatment.

Treatment of early-stage mycosis fungoides: results from the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study.

BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). OBJECTIVES: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. METHODS: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. RESULTS: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease. CONCLUSIONS: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues.

Monotherapy and combination therapy with acitretin for mycosis fungoides: results of a retrospective, multicentre study.

BACKGROUND: Retinoids have long been used in the treatment of cutaneous T-cell lymphomas. However, data on acitretin use for mycosis fungoides (MF) are very limited. OBJECTIVES: To evaluate treatment outcomes of acitretin in patients with MF attending three academic referral centres in different regions of Greece. METHODS: Data on effectiveness, safety and drug survival of acitretin as monotherapy or as adjuvant regimen were collected in a multicentre, register-based, retrospective study. RESULTS: Overall, 128 patients (64.8% male; mean age at MF diagnosis 59.7 years) were included. Folliculotropic MF was present in 24 (18.8%) cases. Most patients (n = 118; 92.2%) had early-stage disease (≤IIA) at acitretin initiation. In all, 28 (21.9%) patients received acitretin monotherapy, while 100 (78.1%) subjects on acitretin concomitantly received phototherapy (n = 65; 50.8%) or topical steroids (n = 27; 21.1%). Acitretin was given as a first-line agent in 73 (57%) cases. A 77.3% overall response rate was noted: 44.5% and 32.8% for complete and partial responses, respectively. Acitretin was more effective as first-line than as a subsequent agent (P = 0.008). A trend towards better response was observed in the combination arm compared to patients receiving acitretin alone (P = 0.056). Median time to best response was 6.9 months (IQR 4.4-9.4); median duration of response was 23.7 months (IQR 11.9-35.4). Overall, the mean length of all treatment patterns was 569 days (SD 718.8). Therapy was discontinued in 5 (3.9%) cases due to drug intolerance. Adverse effects were recorded in 62 (48.4%) cases with dyslipidaemia (n = 31; 24.2%), xerosis (n = 24; 18.6%) and hair loss (n = 10; 7.8%) being the most commonly recorded. CONCLUSIONS: Acitretin, either alone or as adjuvant, showed a stable long-term effectiveness in this cohort, especially when used in the first-line setting. This RAR-selective agonist may serve as an attractive option for treatment of MF and should be further evaluated.

External cephalic version at term: a cohort study of 18 years' experience.

OBJECTIVE: To analyse the outcome of referrals for external cephalic version (ECV). DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Major university hospital, UK. SAMPLE: Women with non-cephalic presentation at term and no prior caesarean, referred to a specialist clinic. METHODS: Details of referrals, ECV attempts, and perinatal outcomes were prospectively collected and analysed. Multivariate binary logistic regression models were created to determine independent predictors of ECV success, reversion, and spontaneous version. MAIN OUTCOME MEASURES: External cephalic version success rates, predictors of success and cephalic presentation at birth, and perinatal outcomes. RESULTS: Three thousand eight had confirmed breech presentation; 2614 women underwent ECV. Ineligibility for ECV occurred in 117 breech presentations (3.9%), and 297 eligible women (10.2%) declined it. ECV was successful in 1280 (49.0%, 95% CI 47.0-50.9%) (40% in nulliparous women; 64% in others); 1234 (97.3%) were cephalic at birth. Spontaneous version after failure occurred in 4.3% and was more common in multiparas (aOR 2.47, 95% CI 1.43-4.26) and those with a posterior fetal back (aOR 6.09, 95% CI 1.90-19.53). Reversion after successful ECV occurred in 2.2%. In women with a successful ECV whose fetus remained cephalic at birth, 85.7% delivered vaginally. The corrected perinatal mortality of the ECV cohort was 0.12%. CONCLUSION: External cephalic version has a low complication rate and is effective for most breech presentations, enabling vaginal birth and avoiding caesarean section. TWEETABLE ABSTRACT: External cephalic version can safely be performed with most breech presentations.

Prognostic indicators for mycosis fungoides in a Greek population.

BACKGROUND: Mycosis fungoides (MF) is an indolent cutaneous lymphoma with excellent prognosis at early stages and much poorer outcome during disease progression. Old age, male sex and folliculotropism have been proposed as relevant prognostic factors; however, their exact effect remains debatable. OBJECTIVES: To evaluate MF prognostic indicators and survival rates in a Greek population. METHODS: Prognostic variables affecting survival rates were studied in 473 patients with MF diagnosed and treated by two academic referral centres in Greece. Kaplan-Meier estimates were used to determine survival rates and progression. The Cox proportional hazards regression model was used to assess prognostic factors. RESULTS: The mean age of diagnosis was 61·7 years (SD 16·33). Five-year disease-specific survival was 96% in patients with stage IA disease and 52% in patients with stage IIB disease. Univariate analysis certified that large-cell transformation, clonal rearrangements of the TCR gene, severe pruritus and presence of plaques were the most important prognostic factors. Folliculotropism altered disease progression only in patients with early-stage disease. The application of the Cutaneous Lymphoma International Prognostic Index (CLIPI) on our late-stage group failed to provide reliable evidence. The current Cutaneous Lymphoma International Consortium (CLIC) prognostic index can efficiently distinguish a low-risk from a high-risk group of patients. Tumour-Node-Metastasis-Blood (TNMB) staging was the most important prognostic factor for survival rates in multivariate analysis. CONCLUSIONS: In our study we validated the current prognostic indicators for MF in a Greek population and identified new potential prognostic factors for survival outcome. Our findings contribute to the ongoing investigation of prognostic indicators of MF, further validation of which is highly needed through prospective studies and among different populations.

C-reactive protein as a predictor of severity of appendicitis.

BACKGROUND: Complex (perforated or gangrenous) appendicitis has a high rate of morbidity in South Africa. METHOD: The study retrospectively reviewed results from January 2013 to December 2015 at Paarl Hospital in the Western Cape province. All patients who had their appendices surgically removed due to suspected appendicitis and who had preoperative results for CRP and WCC were included. Using the area under the Receiver Operated Characteristics curve we compared the inflammatory markers of 2 groups with histologically proven appendicitis: those with complex (perforated or gangrenous appendix) and those with uncomplicated appendicitis (inflamed appendix). Youden's J statistic was used to determine the optimal cut-off value above which complex appendicitis would be the most likely diagnosis. RESULTS: A total of 591 patients were identified, 385 had results for both WCC and CRP. CRP (AUC 72%) proved to be a fair and WCC (AUC 58%) a poor predictor of complex appendicitis. Cut-off values for CRP and WCC were found to be 215 mg/l and 16.80 109 cells/l respectively. At these threshold values CRP (sensitivity 51.4%, specificity 85.7%, p-value < 0.001, positive predictive value 80.2%, negative predictive value 61%, positive likelihood ratio 3.6 and diagnostic odds ratio 6.35) proved to be much better than WCC (sensitivity 43%, specificity 73.8%, p-value = 0.022, positive predictive value 64.9%, negative predictive value 53.4%, positive likelihood ratio 1.64 and diagnostic odds ratio 2.11) in predicting complex appendicitis. CONCLUSION: CRP is superior to WCC in the differentiation between uncomplicated and complex appendicitis. Using a cut-off value of CRP 215 mg/l is statistically significant in diagnosing complex appendicitis. This value should be used cautiously as many more studies are needed to confirm these findings.

The study of progesterone action in human myometrial explants.

STUDY HYPOTHESIS: Myometrial explants represent a superior model compared with cell culture models for the study of human myometrial progesterone (P4) signalling in parturition. STUDY FINDING: Gene expression analysis showed myometrial explants closely resemble the in vivo condition and the anti-inflammatory action of P4 is not lost with labour onset. WHAT IS KNOWN ALREADY: Circulating P4 levels decline before the onset of parturition in most animals, but not in humans. This has led to the suggestion that there is a functional withdrawal of P4 action at the myometrial level prior to labour onset. However, to date, no evidence of a loss of P4 function has been provided, with studies hampered by a lack of a physiologically relevant model. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Myometrial biopsies obtained at Caesarean section were dissected into explants after a portion was immediately snap frozen (t = 0). Microarray analysis was used to compare gene expression of t = 0 with paired (i) explants, (ii) passage 4 myometrial cell cultures or (iii) the hTERT myometrial cell line. Western blotting and chemokine/cytokine assays were used to study P4 signalling in myometrial explants. MAIN RESULTS AND THE ROLE OF CHANCE: Gene expression comparison of t = 0 to the three models demonstrated that explants more closely resemble the in vivo status. At the protein level, explants maintain both P4 receptor (PR) and glucocorticoid receptor (GR) levels versus t = 0 whereas cells only maintain GR levels. Additionally, treatment with 1 µM P4 led to a reduction in interleukin-1 (IL-1) ß-driven cyclooxygenase-2 in explants but not in cells. P4 signalling in explants was PR-mediated and associated with a repression of p65 and c-Jun phosphorylation. Furthermore, the anti-inflammatory action of P4 was maintained after labour onset. LIMITATIONS/REASONS FOR CAUTION: There is evidence of basal inflammation in the myometrial explant model. WIDER IMPLICATIONS OF THE FINDINGS: Myometrial explants constitute a novel model to study P4 signalling in the myometrium and can be used to further elucidate the mechanisms of P4 action in human labour. LARGE SCALE DATA: Data deposited at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=gvmpggkurbgxfqf&acc=GSE77830. STUDY FUNDING AND COMPETING INTEREST: This work was supported by grants from the Joint Research Committee of the Westminster Medical School Research Trust, Borne (No. 1067412-7; a sub-charity of the Chelsea and Westminster Health Charity) and the Imperial NIHR Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS or the Department of Health. The authors have no conflict of interest.

Epidemiology of respiratory syncytial virus in children in Cyprus during three consecutive winter seasons (2010-2013): age distribution, seasonality and association between prevalent genotypes and disease severity.

This study reports the epidemiology of respiratory syncytial virus (RSV) in hospitalized children in Cyprus over three successive seasons (2010-2013) and the association between prevalent genotypes and disease severity. RSV infections had a circulation pattern from December to March. Most RSV-positive children (83%) were aged <2 years. Genotyping of RSV isolates showed that during the first winter season of the study (2010-2011), the only RSV genotype circulating was GA2 (RSV-A), followed by genotype BA (RSV-B) in the next winter season with only few sporadic cases of GA2. During the last winter season of the study (2012-2013) the newly emerged RSV genotype ON1 (RSV-A) was virtually the only circulating genotype. Children infected with genotype ON1 suffered a significantly milder illness compared to infections with genotypes GA2 and BA with a higher percentage of BA-infected children requiring oxygen. Our findings are in contrast to the majority of published reports that suggest RSV-A causes more severe illness than RSV-B. Therefore, further investigation of the association between RSV genotypes and disease severity is required, as it might affect treatment strategies in the future.

On the output factor measurements of the CyberKnife iris collimator small fields: Experimental determination of the k(Q(clin),Q(msr) ) (f(clin),f(msr) ) correction factors for microchamber and diode detectors.

PURPOSE: To measure the output factors (OFs) of the small fields formed by the variable aperture collimator system (iris) of a CyberKnife (CK) robotic radiosurgery system, and determine the k(Q(clin),Q(msr) ) (f(clin),f(msr) ) correction factors for a microchamber and four diode detectors. METHODS: OF measurements were performed using a PTW PinPoint 31014 microchamber, four diode detectors (PTW-60017, -60012, -60008, and the SunNuclear EDGE detector), TLD-100 microcubes, alanine dosimeters, EBT films, and polymer gels for the 5 mm, 7.5 mm, 10 mm, 12.5 mm, and 15 mm iris collimators at 650 mm, 800 mm, and 1000 mm source to detector distance (SDD). The alanine OF measurements were corrected for volume averaging effects using the 3D dose distributions registered in polymer gel dosimeters. k(Q(clin),Q(msr) ) (f(clin),f(msr) ) correction factors for the PinPoint microchamber and the diode dosimeters were calculated through comparison against corresponding polymer gel, EBT, alanine, and TLD results. RESULTS: Experimental OF results are presented for the array of dosimetric systems used. The PinPoint microchamber was found to underestimate small field OFs, and a k(Q(clin),Q(msr) ) (f(clin),f(msr) ) correction factor ranging from 1.127 ± 0.022 (for the 5 mm iris collimator) to 1.004 ± 0.010 (for the 15 mm iris collimator) was determined at the reference SDD of 800 mm. The PinPoint k(Q(clin),Q(msr) ) (f(clin),f(msr) ) correction factor was also found to increase with decreasing SDD; k(Q(clin),Q(msr) ) (f(clin),f(msr) ) values equal to 1.220 ± 0.028 and 1.077 ± 0.016 were obtained for the 5 mm iris collimator at 650 mm and 1000 mm SDD, respectively. On the contrary, diode detectors were found to overestimate small field OFs and a correction factor equal to 0.973 ± 0.006, 0.954 ± 0.006, 0.937 ± 0.007, and 0.964 ± 0.006 was measured for the PTW-60017, -60012, -60008 and the EDGE diode detectors, respectively, for the 5 mm iris collimator at 800 mm SDD. The corresponding correction factors for the 15 mm iris collimator were found equal to 0.997 ± 0.010, 0.994 ± 0.009, 0.988 ± 0.010, and 0.986 ± 0.010, respectively. No correlation of the diode k(Q(clin),Q(msr) ) (f(clin),f(msr) ) correction factors with SDD was observed. CONCLUSIONS: This work demonstrates an experimental procedure for the determination of the k(Q(clin),Q(msr) ) (f(clin),f(msr) ) correction factors required to obtain small field OF results of increased accuracy.

Quantifying the bystander-effect of 2.5G mobile telephones on the speech perception of digital hearing aid users.

OBJECTIVE: To quantify the bystander-effect of 2.5G mobile telephones (2.5G-MTs) on the speech perception of digital hearing-aid (dHA) users. Differences in the susceptibility of behind-the-ear (BTE) compared to in-to-the-ear (ITE) dHAs were also assessed. MATERIALS/METHODS: Prospective-comparative study conducted at a tertiary referral centre (ENT Department) and a HA-fitting laboratory. Key-word recognition scores from open-sentence lists were calculated. Power-analysis determined that a minimum of 60 subjects with SNHL (30 in each group), using either BTE or ITE dHAs, were required for reliable study outcomes. Sixty-four adults were tested with a functioning 2.5G-MT at almost physical contact with their ear; thirty subjects used BTE and 34 ITE dHAs. MAIN OUTCOME MEASURES: Aided word recognition score differences between studied groups and within each group, while a 2.5G-MT was activated. Cut-off inclusion criterion regarding baseline aided word recognition score was 75%. RESULTS: Baseline aided word recognition scores for ITE dHAs were better compared to BTE ones (p < 0.01). Following the 2.5G-MT activation, this difference disappeared. No statistically significant difference in word recognition was observed between the examined groups, or within the BTE group, from the bystander-effect of the 2.5G-MT. ITE dHAs proved more susceptible to electromagnetic interference (p < 0.05). CONCLUSION: The bystander-effect of 2.5G-MTs on the speech perception of dHA users is either minimal, or not significant. The observed compatibility has a positive impact on the lives of millions of people worldwide. The long-standing theory of more interference in BTE compared to ITE HAs is not confirmed by the results of the present study. EBM level of evidence: 2c.

Gall bladder torsion masquerading as appendicitis in a teenage boy.

SUMMARY: This report describes acute gallbladder torsion in a previously healthy 16-year-old male. The patient presented with acute right-sided abdominal pain in keeping with acute appendicitis and was taken for a diagnostic laparoscopy where an intraoperative diagnosis of gallbladder torsion was made. This case highlights a very rare surgical presentation in an uncommon patient profile. It highlights the benefit of diagnostic laparoscopy in a resource-constrained facility.

Dosimetric accuracy of a deterministic radiation transport based 192Ir brachytherapy treatment planning system. Part II: Monte Carlo and experimental verification of a multiple source dwell position plan employing a shielded applicator.

PURPOSE: The aim of this work is the dosimetric validation of a deterministic radiation transport based treatment planning system (BRACHYVISION v. 8.8, referred to as TPS in the following) for multiple 192Ir source dwell position brachytherapy applications employing a shielded applicator in homogeneous water geometries. METHODS: TPS calculations for an irradiation plan employing seven VS2000 192Ir high dose rate (HDR) source dwell positions and a partially shielded applicator (GM11004380) were compared to corresponding Monte Carlo (MC) simulation results, as well as experimental results obtained using the VIP polymer gel-magnetic resonance imaging three-dimensional dosimetry method with a custom made phantom. RESULTS: TPS and MC dose distributions were found in agreement which is mainly within +/- 2%. Considerable differences between TPS and MC results (greater than 2%) were observed at points in the penumbra of the shields (i.e., close to the edges of the "shielded" segment of the geometries). These differences were experimentally verified and therefore attributed to the TPS. Apart from these regions, experimental and TPS dose distributions were found in agreement within 2 mm distance to agreement and 5% dose difference criteria. As shown in this work, these results mark a significant improvement relative to dosimetry algorithms that disregard the presence of the shielded applicator since the use of the latter leads to dosimetry errors on the order of 20%-30% at the edge of the "unshielded" segment of the geometry and even 2%-6% at points corresponding to the potential location of the target volume in clinical applications using the applicator (points in the unshielded segment at short distances from the applicator). CONCLUSIONS: Results of this work attest the capability of the TPS to accurately account for the scatter conditions and the increased attenuation involved in HDR brachytherapy applications employing multiple source dwell positions and partially shielded applicators.

Inhibition of lipoxygenase (LOX) and anticancer activity caused by gold(I) mixed ligands complexes of triphenylphosphine and thioamides.

Four mixed ligand gold(I) complexes with the thioamides 2-mercapto-thiazolidine (mtzdH), 2-mercapto-benzothiazole (mbztH) and 5-chloro-2-mercapto-benzothiazole (ClmbztH) and triphenylphosphine (tpp) of formulae [Au(tpp)Cl] (1) [Au(tpp)(mtzd)] (2), [Au(tpp)(mbzt)] (3) and [Au(tpp)(Clmbzt)] (4), already known, were used to study their mechanism of inhibition activity towards the catalytic oxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX), kinetically and theoretically. The results are compared to those of cisplatin. In addition, the anticancer cell screening results against leimyosarcoma (LMS) cells have shown that 2-4 complexes were more active than cisplatin. The uptake of complexes in LMS cells were also studied with electrospray ionisation mass spectrometry spectroscopy.

Streamlining outpatient urogynaecology: a novel approach.

With population ageing, service expansion in urogynaecology is a necessity. The aim of this study was to determine the feasibility of a nurse specialist-led triage clinic as a novel way of outpatient care provision. Review of the patient pathway through the service over a 15-month period demonstrated effective patient management with timely order of investigations and treatment initiation, improved continuity of care, a reduction in the volume of medical consultations and high patient satisfaction. In conclusion, specialist nurse clinics provide a sustainable method of service expansion, while simultaneously facilitating service transfer to the community in line with current healthcare policy.

On the implementation of a recently proposed dosimetric formalism to a robotic radiosurgery system.

PURPOSE: The aim of this work is to implement a recently proposed dosimetric formalism for nonstandard fields to the calibration and small field output factor measurement of a robotic stereotactic radiosurgery system. METHODS: Reference dosimetry measurements were performed in the nonstandard, 60 mm diameter machine specific reference (msr) field using a Farmer ion chamber, five other cylindrical chambers with cavity lengths ranging from 16.25 down to 2.7 mm, and alanine dosimeters. Output factor measurements were performed for the 5, 7.5, 10, and 15 mm field sizes using microchambers, diode detectors, alanine dosimeters, TLD microcubes, and EBT Gafchromic films. Measurement correction factors as described in the proposed formalism were calculated for the ion chamber and diode detector output factor measurements based on published Monte Carlo data. Corresponding volume averaging correction factors were calculated for the alanine output factor measurements using 3D dose distributions, measured with polymer gel dosimeters. RESULTS: Farmer chamber and alanine reference dosimetry results were found in close agreement, yielding a correction factor of k(Q(msr),Q)(f(msr),f(ref)) = 0.999 +/- 0.016 for the chamber readings. These results were also found to be in agreement within experimental uncertainties with corresponding results obtained using the shorter cavity length ionization chambers. The mean measured dose values of the latter, however, were found to be consistently greater than that of the Farmer chamber. This finding, combined with an observed inverse relationship between the mean measured dose and chamber cavity length that follows the trend predicted by theoretical volume averaging calculations in the msr field, implies that the Farmer k(Q(msr),Q)(f(msr),f(ref)) correction is greater than unity. Regarding the output factor results, deviations as large as 33% were observed between the different dosimeters used. These deviations were substantially decreased when appropriate correction factors were applied to the measured microchamber, diode, and alanine values. After correction, all diode and microchamber measured output factors agreed within 1.6% with the corresponding alanine measurements, and within 3.1% with the TLD measurements. The weighted mean output factors were 0.681 +/- 0.001, 0.824 +/- 0.001, 0.875 +/- 0.001, and 0.954 +/- 0.001 for the 5, 7.5, 10, and 15 mm beams, respectively. CONCLUSIONS: The comparison of Farmer chamber measurements versus alanine reference dosimetry validates the use of the former for dosimetry in the msr field of this treatment delivery system. The corresponding results of this work obtained using chambers with different cavity lengths, combined with previous literature findings, suggest that a k(Q(msr),Q)(f(msr),f(ref)) Farmer chamber dose response correction factor of 1.01 may improve calibration measurement accuracy when using the proposed dosimetric formalism. The k(Q(msr),Q)(f(msr),f(ref)) correction factor is within 0.5% from unity for ion chambers with cavity lengths less than 10 mm. Substantial improvements in small field output factor measurement accuracy can be obtained when using microchambers and diodes by applying appropriately calculated correction factors to the detector measurements according to the proposed dosimetric formalism, and their routine use is therefore recommended.

Dosimetric accuracy of a deterministic radiation transport based 192Ir brachytherapy treatment planning system. Part I: single sources and bounded homogeneous geometries.

PURPOSE: The aim of this work is to validate a deterministic radiation transport based treatment planning system (TPS) for single 192Ir brachytherapy source dosimetry in homogeneous water geometries. METHODS: TPS results were obtained using the deterministic radiation transport option of a BRACHYVISION v. 8.8 system for three characteristic source designs (VS2000, GMPlus HDR, and GMPlus PDR) with each source either centered in a 15 cm radius spherical water phantom, or positioned at varying distance away from the phantom center. Corresponding MC simulations were performed using the MCNPX code v.2.5.0 and source geometry models prepared using information provided by the manufacturers. RESULTS: Comparison in terms of the AAPM TG-43 dosimetric formalism quantities, as well as dose rate distributions per unit air kerma strength with a spatial resolution of 0.1 cm, yielded close agreement between TPS and MC results for the sources centered in the phantom. Besides some regions close to the source longitudinal axes where discrepancies could be characterized as systematic, overall agreement for all three sources studied is comparable to the statistical (type A) uncertainty of MC simulations (1% at the majority of points in the geometry increasing to 2%-3% at points lying both away from the source center and close to the source longitudinal axis). A corresponding good agreement was also found between TPS and MC results for the sources positioned away from the phantom center. CONCLUSIONS: Results of this work attest the capability of the TPS to accurately account for the scatter conditions regardless of the size or shape of a given geometry of dosimetric interest, and the position of a source within it. This is important since, as shown in the literature and summarized also in this work, these factors could introduce a significant dosimetric effect that is currently ignored in clinical treatment planning. It is concluded that the implementation of the deterministic radiation transport option of the BRACHYVISION v. 8.8 system for 192Ir brachytherapy dosimetry in homogeneous water geometries yields results of comparable accuracy to the golden standard of Monte Carlo simulation, in clinically viable calculation times.

Contribution of (99m)Tc-depreotide (Neospect) scintigraphy in lung cancer staging.

PURPOSE: The aim of this study was to evaluate the usefulness of scintigraphy with (99m)Tc-depreotide in the staging of lung cancer, especially in cases where CT findings are doubtful. METHODS: 53 patients with suspected lung cancer were investigated with whole body planar acquisition and single photon emission computed tomography (SPECT) of the thorax after i.v. injection of 740 MBq (99m)Tc-depreotide (Neospect). The results were compared with CT and correlated with histological findings. RESULTS: In 50 of 53 patients the biopsy was positive for bronchogenic carcinoma (31 patients with non small cell lung cancer [NSCLC], 18 with small cell lung cancer (SCLC), and 1 patient with neuroendocrine cancer). In the remaining 3, biopsy revealed no bronchogenic carcinoma (3 patients with inflammation). In 2/31 patients with NSCLC and doubtful CT findings, uptake of (99m)Tc-depreotide was the only non invasive reliable staging method. CONCLUSION: It seems that scintigraphy with (99m)Tc-depreotide in patients with SCLC does not change the tumor stage, whereas in NSCLC the contribution of Neospect in lung cancer staging may be a helpful tool, especially in cases where CT alone is unable to distinguish between IIIA and IIIB stages (operable from non operable status).

Gamma knife output factor measurements using VIP polymer gel dosimetry.

PURPOSE: Water equivalent polymer gel dosimeters and magnetic resonance imaging were employed to measure the output factors of the two smallest treatment fields available in a Gamma Knife model C radiosurgery unit, those formed employing the 4 and 8 mm final collimator helmets. METHODS: Three samples of the VIP normoxic gel formulation were prepared and irradiated so that a single shot of the field whose output factor is to be measured and a single shot of the reference 18 mm field were delivered in each one. Emphasis is given to the development and benchmarking of a refined data processing methodology of reduced uncertainty that fully exploits the 3D dose distributions registered in the dosimeters. RESULTS: Polymer gel results for the output factor of the 8 mm collimator helmet are found to be in close agreement with the corresponding value recommended by the vendor (0.955 +/- 0.007 versus 0.956, respectively). For the 4 mm collimator helmet, however, polymer gel results suggest an output factor 3% lower than the value recommended by the vendor (0.841 +/- 0.009 versus 0.870, respectively). CONCLUSIONS: A comparison with corresponding measurements published in the literature indicates that output factor results of this work are in agreement with those obtained using dosimetric systems which, besides fine spatial resolution and lack of angular and dose rate dependence of the dosimeter's response, share with polymer gels the favorable characteristic of minimal radiation field perturbation.

Intracerebroventricular endothelin receptor-A blockade in rats decreases phase-II ventricular tachyarrhythmias during acute myocardial infarction.

Endothelin alters central sympathetic responses, but the resultant effects on arrhythmogenesis are unknown. We examined ventricular tachyarrhythmias after endothelin receptor-A blockade in the brain of Wistar rats with acute myocardial infarction. For this aim, BQ-123 (n=6) or phosphate-buffered saline (n=6) were injected intracerebroventricularly. After 10 min, the left coronary artery was ligated, followed by implantation of telemetry transmitters. Electrocardiography and voluntary activity (as a surrogate of acute left ventricular failure) were continuously monitored for 24 h. Infarct-size was similar in the two groups. There were fewer episodes of ventricular tachyarrhythmias of shorter average duration in treated rats, leading to markedly shorter total duration (12.3+/-8.9 s), when compared to controls (546.2+/-130.3 s). Voluntary activity increased in treated rats during the last hours of recording, but bradyarrhythmic episodes were comparable between the two groups. Endothelin receptor-A blockade in the brain of rats decreases the incidence of ventricular tachyarrhythmias post-ligation, without affecting bradyarrhythmic episodes. These findings call for further research on the pathophysiologic role of endothelin during acute myocardial infarction.