ABSTRACT
OBJECTIVES: To compare survival of patients who received LDR prostate brachytherapy relative to that of peers in the general population of England, UK. PATIENTS AND METHODS: Net survival was estimated for 2472 cases treated between 2002 and 2016 using population-based analysis guidelines. Life tables adjusted for social deprivation in England from the Office for National Statistics were used to match patients by affluence based on their postcode. RESULTS: The median (range) age at time of brachytherapy was 66 (55-84) years, 84% resided in Southeast England, 51% under an index of deprivation quintile 5 (most affluent), 55% were clinical stage T1 and the remainder T2. Death from any cause occurred in 270 patients at a median (range) of 7 (1-17) years postimplant. Five and 10-year estimates (95% CI) of overall survival were 96% (95-97) and 90% (89-92), and net survival 103% (102-104) and 109% (107-110) respectively. The net survival remained above 100% in all age-at-treatment and clinical stage groups. CONCLUSION: Net survival above 100% indicates patients survive longer than the matched general population. The study shows for the first time the net survival of patients treated with a radical therapy for localized prostate cancer in England. The impact of treatment choice on the long-term net survival advantage requires further investigation.
Subject(s)
Brachytherapy , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/mortality , Aged , Middle Aged , Aged, 80 and over , England/epidemiology , Survival Rate , Neoplasm Staging , Radiotherapy DosageABSTRACT
PURPOSE: Isolated recurrence in remnants of the seminal vesicles (SV) after treatment of primary prostate cancer (PCa) has become a more frequent entity with the widespread use of more sensitive next-generation imaging modalities. Salvage vesiculectomy is hypothesized to be a worthwhile management option in these patients. The primary goal of this study is to describe the surgical technique of this new treatment option. Secondary outcomes are peri- and post-operative complications and early oncological outcomes. METHODS: Retrospective multicenter study, including 108 patients with solitary recurrence in the SV treated between January 2009 and June 2022, was performed. Patients with local recurrences outside the SVs or with metastatic disease were excluded. Both SVs were resected using a robot-assisted or an open approach. In selected cases, a concomitant lymphadenectomy was performed. RESULTS: Overall, 31 patients (29%) reported complications, all but one grade 1 to 3 on the Clavien-Dindo Scale. A median PSA decrease of 2.07 ng/ml (IQR: 0.80-4.33, p < 0.001), translating into a median PSA reduction of 92% (IQR: 59-98%) was observed. At a median follow-up of 14 months, freedom from secondary treatment was 54%. Lymphadenectomy had a significant influence on PSA reduction (p = 0.018). CONCLUSION: Salvage vesiculectomy for PCa recurrence limited to the SV is a safe procedure with excellent PSA response and is a potential curative treatment in a subset of patients. A concomitant lymphadenectomy can best be performed in all patients that did not underwent one at primary treatment.
Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/surgery , Prostate , Pelvis , Seminal VesiclesABSTRACT
PURPOSE: The Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluated hemi-gland (HG) low-dose-rate prostate brachytherapy (LDR-PB) as a focal approach to control unilateral localized prostate cancer and reduce treatment-related toxicity at 2-years postimplant. Herewith we present further outcomes with a minimum of 5 years post-implant follow-up. METHODS AND MATERIALS: Outcomes of 30 HG implants and 362 whole-gland (WG) brachytherapy controls were monitored with IPSS, urinary Quality-of-Life (QoLU), GI component of EORTC-PR25 (QoLB), and IIEF-5 instruments, and PSA values. The median (range) follow-up for HG and WG cases was 72 (60-96) months and 84 (24-144) months respectively. RESULTS: The IPSS was significantly reduced in HG relative to WG patients and trends indicating improved bowel QoL and erectile function were observed. The mean of change in PSA from baseline to last follow-up was -5.6 and -6.5 in HG and WG respectively (pâ¯=â¯0.1). The mean time to nadir was 4.2 and 4.8 years in HG and WG respectively (pâ¯=â¯0.06). Over time PSA in HG patients mirrored the sustained decline observed in WG cases but levels were higher by an average 0.5 ng/ml over WG controls (p < 0.001). Treatment failure occurred in 2 (6.7%) HG patients and in 20 (5.5%) WG cases. Five-year relapse-free survival was 97% in both groups (pâ¯=â¯0.7). CONCLUSIONS: At 5 years postimplant HG LDR-PB was as effective as WG treatment for control of unilateral localized prostate cancer with moderate improvement in treatment-related symptoms. Importantly, PSA is a valuable marker to assess disease control in this form of focal therapy.
Subject(s)
Brachytherapy , Prostatic Neoplasms , Male , Humans , Brachytherapy/methods , Quality of Life , Neoplasm Recurrence, Local/radiotherapy , Prostatic Neoplasms/radiotherapy , Prostate , Prostate-Specific AntigenABSTRACT
OBJECTIVES: To report clinical and functional outcomes for patients who have undergone salvage robot-assisted seminal vesicle excision (RA-SVE) for the focal treatment of isolated seminal vesical (SV) recurrence after treatment for prostate cancer by low-dose-rate brachytherapy. PATIENTS AND METHODS: Patients with rising prostate-specific antigen (PSA) after low-dose-rate prostate brachytherapy (LDR-PB) underwent multi-parametric magnetic resonance imaging (mp-MRI) of the prostate and 11 C-Choline or 68 Ga-prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) scan, followed by targeted transperineal biopsy of the prostate and SVs. Isolated SV recurrence were identified in 17 (0.38%) LDR-PB patients. These 17 patients were offered RA-SVE. RESULTS: The median total operative time was 90 min and blood loss 50 mL with no postoperative transfusions required. The median hospital stay was 1 day. No intra- or postoperative complications were documented. Continence status was unaffected, no patient required urinary pads. Postoperative pathology confirmed SV invasion in all specimens. Surgical margins were positive in seven (41%) patients. All patients had at least one positive imaging study, although three (18%) mp-MRI and five (29%) PET/CT assessments were negative. One (6%) pre-SVE biopsy was also negative but with positive imaging. Salvage SVE failure, defined as three consecutive PSA rises or the need for further treatment, occurred in six patients of whom three had a positive margin. Overall failure-free survival rates were 86%, 67%, and 53% at 1, 2, and 3 years after SVE, respectively. CONCLUSIONS: Salvage RA-SVE appears to be a safe focal treatment, with very low morbidity, for patients with localised SV recurrence after LDR-PB. It permits deferral of androgen deprivation therapy in selected patients. Bilateral SVE is mandatory. This surgical option should be considered in patients with isolated prostate cancer recurrence to the SV.
Subject(s)
Brachytherapy , Prostatic Neoplasms , Robotic Surgical Procedures , Seminal Vesicles , Androgen Antagonists , Biopsy , Humans , Male , Neoplasm Recurrence, Local/pathology , Positron Emission Tomography Computed Tomography , Prostate/pathology , Prostate-Specific Antigen , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Salvage Therapy/methods , Seminal Vesicles/pathology , Seminal Vesicles/surgeryABSTRACT
OBJECTIVES: To assess the long-term treatment efficacy of low-dose-rate (LDR) brachytherapy for the treatment of localized prostate cancer. PATIENTS AND METHODS: Cause-of-death annotation in our prospective database was supplemented with death certificate information obtained via an internal audit of patients treated from 1999 to 2017 with LDR prostate brachytherapy as monotherapy or as combination with androgen deprivation therapy and/or external beam radiotherapy. Overall and disease-specific survival were the primary outcomes, estimated with Kaplan-Meier and competing risks multi-state models. Clinical variables influencing mortality were assessed with Cox proportional hazards regression in a sub-analysis of men to assess the predictive value of prostate-specific antigen (PSA) level at 48 months post implant. RESULTS: The audit process began in October 2017 and culminated in June 2020 with a curated series of 2936 patients. All-cause and prostate cancer-specific death prevalence were 11% and 2.9%, respectively. The median (range) follow-up time was 10 (3-21) years and the median (range) time to death from any cause was 9 (3-21) years. At 15 years post implant the overall and prostate cancer-specific survival probability were 81% and 95%, respectively. The 15-year cumulative incidence rates of death not due and due to prostate cancer were 14% and 5%, respectively. A greater risk of death due to prostate cancer was conferred by increasing age at therapy (hazard ratio [HR] 1.1, P < 0.001), advanced clinical stages relative to T1a-T2a (HR 1.9, P = 0.048 for T2b; HR 2.7, P = 0.023 for T2c-T3b) and a 48-month PSA level >1.0 ng/mL (HR 6.8, P < 0.001). CONCLUSION: This study constitutes the largest retrospective analyses of long-term mortality outcomes from prospectively collected prostate brachytherapy data and confirms the excellent treatment efficacy of LDR prostate brachytherapy for localized prostate cancer. T2 clinical stage subdivisions and 48-month PSA level >1.0 ng/mL appear to be strong indicators of prostate cancer-related survival.
Subject(s)
Brachytherapy , Prostatic Neoplasms , Androgen Antagonists/therapeutic use , Follow-Up Studies , Humans , Male , Prostate-Specific Antigen , Prostatic Neoplasms/therapy , Radiotherapy Dosage , Retrospective StudiesABSTRACT
AIM: To characterize purinergic signaling in overactive bladder (OAB). METHODS: Mucosal biopsies were taken by flexible cystoscopy from patients with storage symptoms referred to Urology Departments of collaborating hospitals. Immunohistochemistry (n = 12) and Western blot analysis (n = 28) were used to establish the qualitative and quantitative expression profile of P2Y6 in human mucosa. Participants from the general population provided a mid-stream urine sample. Bioluminescent assays were used to quantify adenosine triphosphate (ATP; n = 66) and adenosine diphosphate (ADP; n = 60) concentrations, which were normalized to creatinine (Cr) concentration. All participants completed a questionnaire (International Consultation on Incontinence Questionnaire - Overactive Bladder) to score urinary symptoms of OAB. RESULTS: P2Y6 immunoreactivity, more prominent in the urothelium (colocalized with the uroepithelial marker pan-cytokeratin), was more greatly expressed in OAB compared to age- and sex-matched controls (benign prostatic hyperplasia) without OAB symptoms. Mucosal P2Y6 was positively correlated only with incontinence (P = .009). Both urinary ATP and its hydrolysis product, ADP, an agonist to P2Y6, were positively correlated with total OAB symptom score (P = .010 and P = .042, respectively). CONCLUSIONS: The positive correlation of P2Y6 only with incontinence may indicate a different phenotype in OAB wet and warrants further investigation. Positive correlations of ATP and ADP with total OAB symptom score demonstrate upregulation in purinergic signaling in OAB; shown previously only in animal models. Further research is required to validate whether purinoceptors are indeed new therapeutic targets for this highly prevalent symptom complex.
Subject(s)
Adenosine Diphosphate/urine , Adenosine Triphosphate/urine , Mucous Membrane/metabolism , Receptors, Purinergic P2/metabolism , Urinary Bladder, Overactive/metabolism , Urinary Bladder/metabolism , Urinary Incontinence/metabolism , Urothelium/metabolism , Adult , Aged , Case-Control Studies , Creatinine/urine , Cystoscopy , Female , Humans , Male , Middle Aged , Prostatic Hyperplasia/metabolism , Prostatic Hyperplasia/pathology , Prostatic Hyperplasia/physiopathology , Surveys and Questionnaires , Urinary Bladder/pathology , Urinary Bladder/physiopathology , Urinary Bladder, Overactive/pathology , Urinary Bladder, Overactive/physiopathology , Urinary Incontinence/pathology , Urinary Incontinence/physiopathologyABSTRACT
OBJECTIVES: To report clinical outcomes of the Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluating treatment-related toxicity and effectiveness of hemi-gland (HG) low-dose-rate (LDR) prostate brachytherapy as a focal approach to control unilateral localised prostate cancer. PATIENTS AND METHODS: Single institution phase IIS pilot study of patients treated with focal 4D Brachytherapy™ (BXTAccelyon, Burnham, Buckinghamshire, UK). The primary outcome was patient-reported toxicity 24 months after implant. The secondary outcome was assessment of disease control. Outcomes in HG patients were compared to whole-gland (WG) controls obtained from our prospective cohort registry by negative binomial and linear regression models. RESULTS: Pre-treatment demography was similar between the 30 HG patients and 362 WG controls. Post-implant dosimetry was similar for the prostate gland target volumes and significantly reduced for the urethra and bowel in HG patients relative to WG controls, but this did not translate into a difference in post-implant mean symptom scores between the two groups. Nevertheless, the change in score from baseline indicated that the impact on pre-treatment symptom status was less after HG implants. Only HG patients showed a return to baseline urinary scores as early as 12 months. Sexual potency was conserved in 73% and 67% of HG and WG patients, respectively (P = 0.84). Post-implant prostate-specific antigen (PSA) kinetics revealed that baseline PSA was reduced at 24 months by 78% and 88% in HG and WG patients, respectively (P < 0.05). Treatment relapse occurred in one (3%) HG patient 55 months after implant and in nine (3%) WG patients at 32-67 months after implant. CONCLUSION: This pilot study suggests that treatment-related toxicity and biochemical outcomes after HG implants are broadly similar to those observed with WG treatment despite the lower dose delivered by HG implants.
Subject(s)
Brachytherapy/methods , Prostatic Neoplasms/radiotherapy , Brachytherapy/adverse effects , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Prostatic Neoplasms/pathology , Radiotherapy Dosage , Treatment OutcomeABSTRACT
OBJECTIVES: To report clinical outcomes of 125 I low-dose-rate prostate brachytherapy (LDR-PB) as monotherapy or combined with androgen-deprivation therapy (ADT) and/or external beam radiotherapy (EBRT) in high-risk localised prostate cancer. PATIENTS AND METHODS: Analysis of clinical outcomes from a prospective cohort of patients treated with LDR-PB alone or combined treatment in a single institution. Men with a high risk of disease relapse were identified by the National Institute for Health and Care Excellence (NICE) criteria or by the National Comprehensive Cancer Network (NCCN) criteria. Relapse-free survival (RFS), overall survival (OS), prostate cancer-specific survival (PCSS), and metastases-free survival (MFS), were analysed together with patient-reported symptom scores and physician-reported adverse events. RESULTS: The NICE and NCCN criteria identified 267 and 202 high-risk patients, respectively. NICE-defined patients had significantly lower pre-treatment PSA levels, Gleason scores <7, and a greater proportion of patients who received LDR-PB monotherapy. At 9 years after implantation RFS was 89% and 87% in the NICE and NCCN groups, respectively (log-rank P = 0.637), and OS 93% and 94%, respectively (log-rank P = 0.481). All of the survival estimates were similar between LDR-PB monotherapy and combined therapies. Cox proportional hazards regression confirmed RFS was similar between the treatment types. Treatment-related toxicity was also similar between the treatment methods. CONCLUSION: LDR-PB is effective at controlling localised prostate cancer in patients with a high risk of disease relapse. As the present study was not randomised, it is not possible to define those patients who need the addition of ADT and/or EBRT. However, the NICE criteria appear suitable to define treatment options where patients could benefit from LDR-PB as monotherapy or combined treatment. This choice should be discussed with the patient taking into account comorbidities and presence of multiple high-risk factors.
Subject(s)
Androgen Antagonists/therapeutic use , Brachytherapy , Neoplasm Recurrence, Local/prevention & control , Prostatic Neoplasms/therapy , Aged , Aged, 80 and over , Combined Modality Therapy , Humans , Male , Middle Aged , Progression-Free Survival , Prospective Studies , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Radiotherapy Dosage , Secondary PreventionABSTRACT
OBJECTIVES: To report oncological and functional outcomes of men treated with low-dose-rate (LDR) prostate brachytherapy aged ≤60 years at time of treatment. PATIENTS AND METHODS: Of 3262 patients treated with LDR brachytherapy at our centre up to June 2016, we retrospectively identified 597 patients aged ≤60 years at treatment with ≥3-years post-implantation follow-up and four prostate-specific antigen (PSA) measurements, of which one was at baseline. Overall survival (OS), prostate cancer-specific survival (PCSS) and relapse free survival (RFS) were analysed together with prospectively collected physician-reported adverse events and patient-reported symptom scores. RESULTS: The median (range) age was 57 (44-60) years, follow-up was 8.9 (1.5-17.2) years, and PSA follow-up 5.9 (0.8-15) years. Low-, intermediate- and high-risk disease represented 53%, 37% and 10% of the patients, respectively. At 10 years after implantation OS and PCSS were 98% and 99% for low-risk, 99% and 100% for intermediate-risk, and 93% and 95% for high-risk disease, respectively. At 10 years after implantation RFS, using the PSA level nadir plus 2 ng/mL definition, was 95%, 90% and 87% for low-, intermediate-, and high-risk disease, respectively. Urinary stricture was the most common genitourinary adverse event occurring in 19 patients (3.2%). At 5 years after implantation erectile function was preserved in 75% of the patients who were potent before treatment. CONCLUSION: LDR brachytherapy is an effective treatment with long-term control of prostate cancer in men aged ≤60 years at time of treatment. It was associated with low rates of treatment-related toxicity and can be considered a first-line treatment for prostate cancer in this patient group.
Subject(s)
Brachytherapy/adverse effects , Brachytherapy/methods , Prostatic Neoplasms/mortality , Prostatic Neoplasms/radiotherapy , Urogenital System/radiation effects , Adult , Age Factors , Cohort Studies , Databases, Factual , Disease-Free Survival , Dose-Response Relationship, Radiation , Erectile Dysfunction/epidemiology , Erectile Dysfunction/etiology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Prostatic Neoplasms/pathology , Radiotherapy Dosage , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Analysis , TimeABSTRACT
BACKGROUND AND PURPOSE: Advances in magnetic resonance imaging (MRI) and prostate sampling enable early identification of men with low to intermediate risk prostate cancer who are candidates for focal therapies that minimise side effects. We report dosimetry data from a pilot study evaluating the effectiveness of hemi-gland low dose rate (HG-LDR) brachytherapy as a focal therapy approach to control unilateral localised disease. MATERIAL AND METHODS: Twenty-two men underwent HG-LDR brachytherapy. Multi parametric MRI and transperineal template mapping biopsies were used to identify low volume unilateral disease. Whole gland therapy controls (n=120) were retrospectively obtained. All implants were performed with 4D Brachytherapy. RESULTS: Intraoperative and postimplant dosimetry complied with established brachytherapy parameters. Mean (standard deviation) postoperative D90 for the target hemi-gland was 153.8 (11.3) Gy compared to 47.5 (12.7) Gy for the contralateral hemi-gland (P<0.001). Mean postoperative V100% was 93.1 (3.9) and 24.6 (10.5) for the target and contralateral hemi-glands respectively (P<0.001). Urethra D30 was 150.4 (19.8) Gy and 174.2 (15.0) Gy for hemi-gland and whole gland implants respectively (P<0.001). Significantly reduced dose was also observed for rectum and neurovascular bundles. CONCLUSIONS: HG-LDR focal brachytherapy is feasible with significant reduction in dose to the contralateral hemi-gland and organs at risk.
Subject(s)
Brachytherapy/methods , Prostatic Neoplasms/radiotherapy , Aged , Biopsy/methods , Feasibility Studies , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Organs at Risk/radiation effects , Pilot Projects , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Radiometry/methods , Radiotherapy Dosage , Rectum/radiation effects , Retrospective Studies , Urethra/radiation effectsABSTRACT
Historically, the primary marker of quality for congenital cardiac surgery has been postoperative mortality. The purpose of this study was to determine whether additional markers (10 surgical metrics) independently predict length of stay (LOS), thereby providing specific targets for quality improvement. Ten metrics (unplanned ECMO, unplanned cardiac catheterization, revision of primary repair, delayed closure, mediastinitis, reexploration for bleeding, complete heart block, vocal cord paralysis, diaphragm paralysis, and change in preoperative diagnosis) were defined in 2008 and subsequently collected from 1024 consecutive index congenital cardiac cases, yielding 990 cases. Four patient characteristics and 22 case characteristics were used for risk adjustment. Univariate and multivariable analyses were used to determine independent associations between each metric and postoperative LOS. Increased LOS was independently associated with revision of the primary repair (p = 0.014), postoperative complete heart block requiring a permanent pacemaker (p = 0.001), diaphragm paralysis requiring plication (p < 0.001), and unplanned postoperative cardiac catheterization (p < 0.001). Compared with patients without each metric, LOS was 1.6 (95 % CI 1.1-2.2, p = 0.014), 1.7 (95 % CI 1.2-2.3, p = 0.001), 1.8 (95 % CI 1.4-2.3, p < 0.001), and 2.0 (95 % CI 1.7-2.4, p < 0.001) times as long, respectively. These effects equated to an additional 4.5-7.8 days in hospital, depending on the metric. The other 6 metrics were not independently associated with increased LOS. The quality of surgery during repair of congenital heart disease affects outcomes. Reducing the incidence of these 4 specific surgical metrics may significantly decrease LOS in this population.
Subject(s)
Arrhythmias, Cardiac/epidemiology , Cardiac Surgical Procedures/adverse effects , Heart Defects, Congenital/mortality , Hospital Mortality , Length of Stay , Postoperative Complications/epidemiology , Quality Improvement , Arrhythmias, Cardiac/etiology , Child , Child, Preschool , Female , Heart Defects, Congenital/surgery , Humans , Infant , Linear Models , Male , Oregon , Reoperation , Retrospective Studies , Risk FactorsABSTRACT
PURPOSE: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). METHODS AND MATERIALS: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. RESULTS: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm(3) was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. CONCLUSIONS: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable reduction to organs at risk. Treating smaller targets makes seed positioning more critical.
Subject(s)
Brachytherapy/methods , Organs at Risk/radiation effects , Prostate/radiation effects , Prostatic Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted , Aged , Biopsy , Feasibility Studies , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Monte Carlo Method , Prostate/pathology , Prostatic Neoplasms/pathology , Radiotherapy Dosage , Rectum/radiation effects , Urethra/radiation effectsABSTRACT
We investigated the effect of fetal sheep ductus arteriosus occlusion (DO) on the distribution of cardiac output and left and right ventricular function by tissue and pulsed Doppler at baseline; after 15 and 60 min of DO induced with a vascular occluder; and 15 min after release of DO. Ductal occlusion decreased fetal pO2. Mean left ventricular output increased (p < 0.001) from 725 to 1013 mL/min, and right ventricular (1185 mL/min vs. 552 mL/min) and systemic (1757 mL/min vs. 1013 mL/min) cardiac outputs fell (p < 0.001) after 15 min of DO, compared with baseline. Pulmonary vascular impedance decreased and volume blood flow increased more than threefold during DO, whereas foramen ovale volume blood flow remained unchanged. Left ventricular systolic function was unaffected, whereas isovolumic relaxation velocity deceleration decreased. Right ventricular functional indices remained unchanged. We conclude that DO increased pulmonary volume blood flow, not foramen ovale volume blood flow. Left ventricular output increased, although not as much as right ventricular output fell, resulting in decreased systemic cardiac output. During DO, left ventricular function exhibited diminished relaxation.
Subject(s)
Ductus Arteriosus/diagnostic imaging , Fetal Heart/diagnostic imaging , Heart Ventricles/diagnostic imaging , Ventricular Dysfunction/diagnostic imaging , Animals , Cardiac Output/physiology , Constriction, Pathologic , Disease Models, Animal , Ductus Arteriosus/physiopathology , Echocardiography, Doppler , Female , Fetal Heart/physiopathology , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Pregnancy , Sheep , Ventricular Dysfunction/physiopathologyABSTRACT
OBJECTIVE: To quantify myocardial blood flow in infants and children with mild or moderate aortic stenosis using adenosine-infusion cardiac magnetic resonance. BACKGROUND: It is unclear whether asymptomatic children with mild/moderate aortic stenosis have myocardial abnormalities. In addition, cardiac magnetic resonance-determined normative myocardial blood flow data in children have not been reported. METHODS: We studied 31 infants and children with either haemodynamically normal hearts (n=20, controls) or mild/moderate aortic stenosis (n=11). The left ventricular myocardium was divided into six segments, and the change in average segmental signal intensity during contrast transit was used to quantify absolute flow (ml/g/minute) at rest and during adenosine infusion by deconvolution of the tissue curves with the arterial input of contrast. RESULTS: In all the cases, adenosine was well tolerated without complications. The mean pressure gradient between the left ventricle and the ascending aorta was higher in the aortic stenosis group compared with controls (24 versus 3 mmHg, p<0.001). Left ventricular wall mass was slightly higher in the aortic stenosis group compared with controls (65 versus 50 g/m², p<0.05). After adenosine treatment, both the absolute increase in myocardial blood flow (p<0.0001) and the hyperaemic flow significantly decreased (p<0.001) in children with mild/moderate aortic stenosis compared with controls. CONCLUSION: Abnormal myocardial blood flow in children with mild/moderate aortic stenosis may be an important therapeutic target.
Subject(s)
Adenosine/administration & dosage , Aortic Valve Stenosis/complications , Coronary Circulation/physiology , Heart Ventricles/physiopathology , Ventricular Function, Left/physiology , Adolescent , Blood Flow Velocity , Child , Child, Preschool , Contrast Media , Female , Humans , Infant , MaleABSTRACT
BACKGROUND: Platelet dysfunction resulting from abnormal fluid shear stress has been reported in adults with aortic stenosis. Blood flowing through a congenital heart defect at greater than normal velocity is subjected to increased shear stress. The primary aim was to determine whether peak flow velocity through congenital cardiac lesions predicts preoperative platelet dysfunction. METHODS: The charts of 402 patients who underwent cardiopulmonary bypass and had preoperative platelet function analysis were evaluated. Platelet dysfunction was measured as a prolonged closure time (CT) in seconds with a platelet function analyzer. Echocardiography was used to determine peak velocity. The relationship between peak velocity and CT was analyzed using linear regression and Kaplan-Meier estimation. RESULTS: The distribution of peak velocity was bimodal. The mean velocity of the lower group was 1.9 m/second and the higher group was 4.2 m/second. Univariate analysis showed age, weight, peak velocity, hematocrit, and Risk Adjustment for Congenital Heart Surgery score to be associated with prolonged CT. Using multivariable analysis, prolonged CT was significantly associated with peak velocity (p < 0.001). For each 1m/second increase in peak velocity the CT increased by over 9 seconds (p < 0.001). In addition, a median CT increase of more than 6 seconds was also associated with a 5 percentage point drop in hematocrit (p = 0.04). CONCLUSIONS: Platelet dysfunction is associated with high blood flow velocity through congenital cardiac lesions. Lower preoperative hematocrit was associated with prolonged CT, which may suggest subclinical bleeding secondary to platelet dysfunction.
Subject(s)
Blood Platelet Disorders/diagnosis , Cardiac Surgical Procedures/mortality , Heart Defects, Congenital/surgery , Analysis of Variance , Blood Flow Velocity , Blood Platelet Disorders/mortality , Cardiac Surgical Procedures/methods , Cardiopulmonary Bypass/methods , Cardiopulmonary Bypass/mortality , Child , Child, Preschool , Cohort Studies , Confidence Intervals , Echocardiography, Doppler , Female , Follow-Up Studies , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/mortality , Humans , Infant , Infant, Newborn , Kaplan-Meier Estimate , Male , Platelet Function Tests , Predictive Value of Tests , Preoperative Period , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Patients undergoing the Fontan procedure may have extended hospital stay due to various postoperative factors including prolonged chest tube drainage. Our aim was to determine the efficacy of our Fontan management protocol in reducing chest tube drainage and length of stay. METHODS: Patients who underwent a Fontan procedure at our institution from June 2008 to September 2013 were analyzed (n = 42). We currently manage our patients according to the PORTLAND protocol: Peripheral vasodilation, Oxygen, Restriction of fluids, Technique of surgery, Low-fat diet, Anticoagulation (including antithrombin III management), No ventilator, and Diuretics. Group A (n = 28) had surgery prior to initiation of this protocol; group B (n = 14) had surgery during the current protocol era. RESULTS: The median number of chest tube days was lower in group B (6 vs 11 days, p < 0.001) as was the total indexed drainage (126 vs 259 mL/kg, p < 0.001). Patients in group B had shorter intensive care unit length of stay (4 vs 7 days, p = 0.004) and hospital length of stay (8 vs 13 days, p = 0.001). Group B had higher preoperative common atrial pressures (7.0 vs 5.8 mm Hg, p = 0.017), end-diastolic pressures (9 vs 7 mm Hg, p = 0.026), and trended toward higher pulmonary artery pressures (11.5 vs 9.5 mm Hg, p = 0.077). There was no statistically significant difference in age, weight, transpulmonary gradient, or pulmonary vascular resistance between groups. CONCLUSIONS: The PORTLAND protocol has improved early outcomes after the Fontan procedure. Chest tube drainage and duration, and both intensive care unit and hospital length of stay have been reduced since initiation of this protocol.