342 research outputs found
Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer
<p>Abstract</p> <p>Background</p> <p>The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory.</p> <p>Findings</p> <p>Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011) was 60 months, with median survival from RT 42 months.</p> <p>Conclusion</p> <p>Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.</p
Interpolated wave functions for nonadiabatic simulations with the fixed-node quantum Monte Carlo method
Simulating nonadiabatic effects with many-body wave function approaches is an
open field with many challenges. Recent interest has been driven by new
algorithmic developments and improved theoretical understanding of properties
unique to electron-ion wave functions. Fixed-node diffusion Monte Caro is one
technique that has shown promising results for simulating electron-ion systems.
In particular, we focus on the CH molecule for which previous results suggested
a relatively significant contribution to the energy from nonadiabatic effects.
We propose a new wave function ansatz for diatomic systems which involves
interpolating the determinant coefficients calculated from configuration
interaction methods. We find this to be an improvement beyond previous wave
function forms that have been considered. The calculated nonadiabatic
contribution to the energy in the CH molecule is reduced compared to our
previous results, but still remains the largest among the molecules under
consideration.Comment: 7 pages, 3 figure
Can prophylactic breast irradiation contribute to cardiac toxicity in patients with prostate cancer receiving androgen suppressing drugs?
<p>Abstract</p> <p>Background</p> <p>Androgen suppression treatment (AST) might increase the risk of cardiac morbidity in prostate cancer patients. Possible explanations were provided, however, they disregard the potential contribution of prophylactic radiotherapy to the mamillary regions (PMRT, prescribed to avoid gynecomastia).</p> <p>Methods</p> <p>We studied the exposure of the heart in a typical electron beam PMRT setting by evaluating computed tomography (CT) scans in 40 non-cancer patients (age 65 and 75 years in 50% each) and 17 prostate cancer patients. Five of the younger, 7 of the older and 4 of the cancer patients had significant cardiac disease.</p> <p>Results</p> <p>The median distance between skin and outer heart contour decreased with age. In all three groups, patients with cardiac morbidity had smaller distances. When using the CT-determined PMRT beam energy, 10% of the younger, 15% of the older and none of the prostate cancer patients would receive approximately 50% of the prescription dose to a part of the heart (2 had no history of cardiac disease). When using the clinically rather than CT-determined beam energy, as often done in daily practice, an additional 12.5% of the non-cancer and 12% of the prostate cancer patients would be exposed to comparably high doses.</p> <p>Conclusion</p> <p>The present data provide preliminary evidence that PMRT might be a factor that contributes to cardiac side effects. Previous studies that established a relationship between AST and cardiac morbidity did not include information on delivery of PMRT.</p
Expression of Androgen Receptor Splice Variants in Prostate Cancer Bone Metastases is Associated with Castration-Resistance and Short Survival
Background: Constitutively active androgen receptor variants (AR-V) lacking the ligand binding domain (LBD) may promote the development of castration-resistant prostate cancer (CRPC). The expression of AR-Vs in the clinically most important metastatic site, the bone, has, however, not been well documented. Our aim was therefore to compare levels of AR-Vs in hormone-naive (HN) and CRPC bone metastases in comparison to primary PC and non-malignant prostate tissue, as well as in relation to AR protein expression, whole-genome transcription profiles and patient survival. Methodology/Principal Findings: Hormone-naı¨ve (n = 10) and CRPC bone metastases samples (n = 30) were obtained from 40 patients at metastasis surgery. Non-malignant and malignant prostate samples were acquired from 13 prostatectomized men. Levels of full length AR (ARfl) and AR-Vs termed AR-V1, AR-V7, and AR-V567es mRNA were measured with RT-PCR and whole-genome transcription profiles with an Illumina Beadchip array. Protein levels were examined by Western blotting and immunohistochemistry. Transcripts for ARfl, AR-V1, and AR-V7 were detected in most primary tumors and metastases, and levels were significantly increased in CRPC bone metastases. The AR-V567es transcript was detected in 23% of the CRPC bone metastases only. A sub-group of CRPC bone metastases expressed LBD-truncated AR proteins at levels comparable to the ARfl. Detectable AR-V567es and/or AR-V7 mRNA in the upper quartile, seen in 1/3 of all CRPC bone metastases, was associated with a high nuclear AR immunostaining score, disturbed cell cycle regulation and short survival. Conclusions/Significance: Expression of AR-Vs is increased in CRPC compared to HN bone metastases and associated with a particularly poor prognosis. Further studies are needed to test if patients expressing such AR-Vs in their bone metastases benefit more from drugs acting on or down-stream of these AR-Vs than from therapies inhibiting androgen synthesis
Assessing Perceived Risk and STI Prevention Behavior: A National Population-Based Study with Special Reference to HPV
Aim: This thesis aims to provide a multidimensional assessment of infection risks and
to evaluate strategies for HPV prevention including vaccination with quadrivalent HPVvaccines,
dose-level vaccine effectiveness and condom use in high STI risk situations.
Methods: Multiple population-based registers and questionnaire responses provided data
for this thesis. Various multivariable and univariate regression models were fit.
Findings: Overall, quadrivalent HPV-vaccination was highly effective against genital
warts (GW) also referred to as condyloma, which is the first HPV disease endpoint
possible to measure. However, effectiveness was contingent upon young age-at-first
vaccination, with effectiveness declining steadily the older the age-at-first vaccination.
Among women above 20 years of age there was low to immeasurable effectiveness and
suggestive evidence vaccinations in this age group tended to reach women at high GW
risk. There were marked socioeconomic disparities in the opportunistic (on-demand with
co-pay) vaccination strategy evaluated, with women and girls who have parents with
the highest education level compared to the lowest having a 15 times greater likelihood
to be vaccinated (Study III). Once vaccination was initiated, however, high parental
education level was unrelated to vaccination completion. Maximum protection against
GW was found among girls vaccinated under the age of 17 who had received three doses
of the vaccine. No differences in effectiveness were found for girls who received twodoses
between ages 10-16 with that of those who received three-doses between ages 17-
19 (Study IV). GW affects more men than women in Sweden as of 2010 with 453 per
100 000 men and 365 per 100 000 women treated. A decline between 25-30% was seen
between 2006 and 2010 among women in the age groups with the highest vaccination
coverage. No decline was found amongst men and their GW incidence has steadily
increased between 2006 and 2010 (Study II). Reported condom use in high risk situations
was low among both men and women, with 41% of men and 34% of women reporting
always/almost always condom use with temporary partners. STI risk perception was also
low, with approximately 10% of sexually active respondents considering themselves at
large risk of contracting an STI. There was no association between men’s condom use and
their STI risk perception but there was an association for women (Study I).
Conclusions: Results suggest that males bear a substantial burden of HPV-related
condyloma where incidence has dropped among women. When planning HPVvaccination
among females, efforts should target girls under age 14 for maximum
effectiveness. Quadrivalent HPV-vaccination offers most protection against condyloma at
three doses. Gross social inequity was found with opportunistic HPV-vaccination. There
were large gender differences in factors associated with condom use in high risk situations
and STI risk perceptions
Theoretical investigation of the electronic structure of Fe(II) complexes at spin-state transitions
The electronic structure relevant to low spin (LS)high spin (HS) transitions in Fe(II) coordination compounds with a FeN6 core are studied. The selected [Fe(tz)6]2+(1) (tz=1H-tetrazole), [Fe(bipy)3]2+(2) (bipy=2,2’-bipyridine) and [Fe(terpy)2]2+ (3) (terpy=2,2’:6’,2’’-terpyridine) complexes have been actively studied experimentally, and with their respective mono-, bi-, and tridentate ligands, they constitute a comprehensive set for theoretical case studies. The methods in this work include density functional theory (DFT), time-dependent DFT (TD-DFT) and multiconfigurational second order perturbation theory (CASPT2). We determine the structural parameters as well as the energy splitting of the LS-HS states (ΔEHL) applying the above methods, and comparing their performance. We also determine the potential energy curves representing the ground and low-energy excited singlet, triplet, and quintet d6 states along the mode(s) that connect the LS and HS states. The results indicate that while DFT is well suited for the prediction of structural parameters, an accurate multiconfigurational approach is essential for the quantitative determination of ΔEHL. In addition, a good qualitative agreement is found between the TD-DFT and CASPT2 potential energy curves. Although the TD-DFT results might differ in some respect (in our case, we found a discrepancy at the triplet states), our results suggest that this approach, with due care, is very promising as an alternative for the very expensive CASPT2 method. Finally, the two dimensional (2D) potential energy surfaces above the plane spanned by the two relevant configuration coordinates in [Fe(terpy)2]2+ were computed both at the DFT and CASPT2 levels. These 2D surfaces indicate that the singlet-triplet and triplet-quintet states are separated along different coordinates, i.e. different vibration modes. Our results confirm that in contrast to the case of complexes with mono- and bidentate ligands, the singlet-quintet transitions in [Fe(terpy)2]2+ cannot be described using a single configuration coordinate
Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.
BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700
Single blind randomized Phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial): study protocol for a randomized controlled trial
Background: The treatment results of external beam radiotherapy for intermediate and high risk prostate cancer patients are insufficient with five-year biochemical relapse rates of approximately 35%. Several randomized trials have shown that dose escalation to the entire prostate improves biochemical disease free survival. However, further dose escalation to the whole gland is limited due to an unacceptable high risk of acute and late toxicity. Moreover, local recurrences often originate at the location of the macroscopic tumor, so boosting the radiation dose at the macroscopic tumor within the prostate might increase local control. A reduction of distant metastases and improved survival can be expected by reducing local failure. The aim of this study is to investigate the benefit of an ablative microboost to the macroscopic tumor within the prostate in patients treated with external beam radiotherapy for prostate cancer.Methods/Design: The FLAME-trial (Focal Lesion Ablative Microboost in prostatE cancer) is a single blind randomized controlled phase III trial. We aim to include 566 patients (283 per treatment arm) with intermediate or high risk adenocarcinoma of the prostate who are scheduled for external beam radiotherapy using fiducial markers for position verification. With this number of patients, the expected increase in five-year freedom from biochemical failure rate of 10% can be detected with a power of 80%. Patients allocated to the standard arm receive a dose of 77 Gy in 35 fractions to the entire prostate and patients in the experimental arm receive 77 Gy to the entire prostate and an additional integrated microboost to the macroscopic tumor of 95 Gy in 35 fractions. The secondary outcome measures include treatment-related toxicity, quality of life and disease-specific survival. Furthermore, by localizing the recurrent tumors within the prostate during follow-up and correlating this with the delivered dose, we can obtain accurate dose-effect information for both the macroscopic tumor and subclinical disease in prostate cancer. The rationale, study design and the first 50 patients included are described.Biological, physical and clinical aspects of cancer treatment with ionising radiatio
Bladder Sparing Approaches for Muscle-Invasive Bladder Cancers.
OPINION STATEMENT: Organ preservation has been increasingly utilised in the management of muscle-invasive bladder cancer. Multiple bladder preservation options exist, although the approach of maximal TURBT performed along with chemoradiation is the most favoured. Phase III trials have shown superiority of chemoradiotherapy compared to radiotherapy alone. Concurrent chemoradiotherapy gives local control outcomes comparable to those of radical surgery, but seemingly more superior when considering quality of life. Bladder-preserving techniques represent an alternative for patients who are unfit for cystectomy or decline major surgical intervention; however, these patients will need lifelong rigorous surveillance. It is important to emphasise to the patients opting for organ preservation the need for lifelong bladder surveillance as risk of recurrence remains even years after radical chemoradiotherapy treatment. No randomised control trials have yet directly compared radical cystectomy with bladder-preserving chemoradiation, leaving the age-old question of superiority of one modality over another unanswered. Radical cystectomy and chemoradiation, however, must be seen as complimentary treatments rather than competing treatments. Meticulous patient selection is vital in treatment modality selection with the success of recent trials within the field of bladder preservation only being possible through this application of meticulous selection criteria compared to previous decades. A multidisciplinary approach with radiation oncologists, medical oncologists, and urologists is needed to closely monitor patients who undergo bladder preservation in order to optimise outcomes
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