Salvage lymph node dissection for prostate cancer nodal recurrence detected by 11C-choline positron emission tomography/computerized tomography.

PURPOSE: We report salvage lymph node dissections for prostate cancer nodal recurrence detected by (11)C-choline positron emission tomography/computerized tomography in the setting of increasing prostate specific antigen after radical prostatectomy. MATERIALS AND METHODS: Retrospective chart review was performed for all patients who underwent salvage lymph node dissection for prostate cancer nodal recurrence. Only patients previously treated with radical prostatectomy were included in the study and those with evidence of local recurrence were excluded from analysis. Primary end points included biochemical recurrence, systemic progression and cancer specific mortality. RESULTS: From 2009 to 2013, 52 men underwent salvage lymph node dissection. Before salvage lymph node dissection 78.8% (41 of 52) had some form of therapy after radical prostatectomy. Median age at salvage lymph node dissection was 60 years and median prostate specific antigen was 2.2 ng/ml (IQR 1.4-3.7). The median number of lymph nodes dissected was 21.5 (IQR 16-30) and the median number of positive nodes was 3.5 (IQR 1.2-6.5). Since salvage lymph node dissection 46.2% of the men (24 of 52) have had no further treatment, 34.6% (18 of 52) are on hormonal therapy and 19.2% (10 of 52) have received multiple different treatments. At the last followup at a median of 20 months (IQR 8-33), 57.7% (30 of 52) had prostate specific antigen remain less than 0.2 ng/ml, 75% (39 of 52) remained free of systemic progression and 96.2% of the men (50 of 52) were alive. Two patients died of prostate cancer. Three-year biochemical recurrence-free, systemic progression-free and cancer specific survival was 45.5%, 46.9% and 92.5%, respectively. CONCLUSIONS: This represents the largest U.S. series of salvage lymph node dissection in the setting of lymph node metastatic prostate cancer after radical prostatectomy. Although followup was short and the study lacked a randomized control group, salvage lymph node dissection may represent a valid treatment option.

Use of tumor dynamics to clarify the observed variability among biochemical recurrence nomograms for prostate cancer.

BACKGROUND: Nomograms for biochemical recurrence (BCR) of prostate cancer (PC) after radical prostatectomy can yield very different prognoses for individual patients. Since the nomograms are optimized on different cohorts, the variations may be due to differences in patient risk-factor distributions. In addition, the nomograms assign different relative scores to the same PC risk factors and rarely stratify for tumor growth rate. METHODS: We compared BCR-free probabilities from the GPSM model with a cell kinetics (CK) model that uses the individual's tumor state and growth rate. We first created a cohort of 143 patients that reproduced the GPSM patient distribution in Gleason score, Prostate specific antigen (PSA), Seminal vesicle involvement and Margin status since they form the GPSM score. We then performed 143 CK calculations to determine BCR-free probabilities for comparison with the GPSM results for all scores and with four other prominent nomograms for a high-risk patient. RESULTS: The BCR-free probabilities from the CK model agree within 10% with those from the GPSM study for all scores once the CK model parameters are stratified in terms of the GPSM risk factors and the PSA doubling time (PSADT). However, the probabilities from widely used nomograms vary significantly. CONCLUSIONS: The CK model reproduces the observed GPSM BCR-free probabilities with a broad stratification of model parameters for PC risk factors and can thus be used to describe PC progression for individual patients. The analysis suggests that nomograms should stratify for PSADT to be predictive.

Magnetic field generation in Rayleigh-Taylor unstable inertial confinement fusion plasmas.

Rayleigh-Taylor instabilities (RTI) in inertial confinement fusion implosions are expected to generate magnetic fields. A Hall-MHD model is used to study the field generation by 2D single-mode and multimode RTI in a stratified two-fluid plasma. Self-generated magnetic fields are predicted and these fields grow as the RTI progresses via the ∇n(e)×∇T(e) term in the generalized Ohm's law. Scaling studies are performed to determine the growth of the self-generated magnetic field as a function of density, acceleration, Atwood number, and perturbation wavelength.

Use of the Richtmyer-Meshkov instability to infer yield stress at high-energy densities.

We use the Richtmyer-Meshkov instability (RMI) at a metal-gas interface to infer the metal's yield stress (Y) under shock loading and release. We first model how Y stabilizes the RMI using hydrodynamics simulations with a perfectly plastic constitutive relation for copper (Cu). The model is then tested with molecular dynamics (MD) of crystalline Cu by comparing the inferred Y from RMI simulations with direct stress-strain calculations, both with MD at the same conditions. Finally, new RMI experiments with solid Cu validate our simulation-based model and infer Y~0.47 GPa for a 36 GPa shock.

A cell kinetics model for prostate cancer and its application to clinical data and individual patients.

A cell kinetics model is developed to describe the evolution of prostate cancer (PC) from diagnosis to PC specific death. Such a model can be used to estimate an individual's eventual outcome and thus to inform decisions about therapy. To describe the observed clinical progression, the model must postulate three PC cell populations that are (1) local to the prostate and sensitive to hormones, (2) regional and hormone sensitive, and (3) systemic and hormone resistant. A set of coupled first-order differential equations describes the exponential growth of a PC tumor as well as its transformation from a local to systemic disease. The time dependence of the solutions is scaled to the doubling time of the prostate specific antigen (PSADT) because it characterizes the tumor growth for the individual. The conversion from local to systemic cell populations is described with a parameter alpha that can be associated with the Gleason score. The model also has three critical cell populations that describe (1) the initiation of the non-local populations, (2) the saturation level of the local tumor, and (3) the cell count likely to cause PC specific death. These parameters are calibrated by reproducing published PC clinical data and survival tables. The model is then applied to individuals with complete PC diagnostic data in order to calculate the progression to PC specific death. One man has early stage PC as described in the 'vignette' patient of Walsh et al. (2007. N. Engl. J. Med. 357, 2696-2705). The second man has a more serious condition and has undergone both local and systemic treatments. Unfortunately, I am that patient.

Correlation effects on the temperature-relaxation rates in dense plasmas.

We present a model for the rate of temperature relaxation between electrons and ions in plasmas. The model includes self-consistently the effects of particle screening, electron degeneracy, and correlations between electrons and ions. We successfully validate the model over a wide range of plasma coupling against molecular-dynamics simulations of classical plasmas of like-charged electrons and ions. We present calculations of the relaxation rates in dense hydrogen and show that, while electron-ion correlation effects are indispensable in classical, like-charged plasmas at any density and temperature, quantum diffraction effects prevail over electron-ion correlation effects in dense hydrogen plasmas.

Rayleigh-Taylor instability with complex acceleration history.

Experiments and numerical simulations are performed on the Rayleigh-Taylor instability with a complex acceleration history g(t) consisting of consecutive periods of acceleration, deceleration, and acceleration. The dominant bubbles and spikes that grow in the initial unstable phase are found to be shredded by the trailing structures during the stable deceleration phase. This reduces their diameter at the front and increases the atomic mixing such that the growth during the final unstable acceleration is retarded. The simulations are able to describe the bubble evolution only if broadband initial perturbations are assumed. Such a complex g(t) is useful for validating mix models.

Limits of the potential flow approach to the single-mode Rayleigh-Taylor problem.

We report on the behavior of a single-wavelength Rayleigh-Taylor flow at late times. The calculations were performed in a long square duct (lambda x lambda x 8lambda), using four different numerical simulations. In contradiction with potential flow theories that predict a constant terminal velocity, the single-wavelength Rayleigh-Taylor problem exhibits late-time acceleration. The onset of acceleration occurs as the bubble penetration depth exceeds the diameter of bubbles, and is observed for low and moderate density differences. Based on our simulations, we provide a phenomenological description of the observed acceleration, and ascribe this behavior to the formation of Kelvin-Helmholtz vortices on the bubble-spike interface that diminish the friction drag, while the associated induced flow propels the bubbles forward. For large density ratios, the formation of secondary instabilities is suppressed, and the bubbles remain terminal consistent with potential flow models.

Single-mode dynamics of the Rayleigh-Taylor instability at any density ratio.

The behavior of a periodic array of Rayleigh-Taylor bubbles (and spikes) of wavelength lambda is investigated at different density ratios using three-dimensional numerical simulations. The scaled bubble and spike velocities (v(b,s)/sqrt[Aglambda/2]), are found to vary with the Atwood number A, and are compared with recent potential flow theories. Simulations at different grid resolutions reveal that the convergence rates of bubble velocities improve with increasing A, while the converse holds true for spike velocities. The asymptotic radius of curvature at the bubble tip is found to be independent of A, consistent with potential flow theory. These results are useful in validating potential flow theory models of the nonlinear stage of the Rayleigh-Taylor instability.

Dependence of turbulent Rayleigh-Taylor instability on initial perturbations.

The dependency of the self-similar Rayleigh-Taylor bubble acceleration constant alpha(b)(identical with [(amplitude)/2] x (displacement) x (Atwood number)) on the initial perturbation amplitude h(0k) is described with a model in which the exponential growth of a small amplitude packet of modes makes a continuous nonlinear transition to its "terminal" bubble velocity proportional, variant Fr[equal to(Froude number)(1/2)]. Then, by applying self-similarity (diameter proportional, variant amplitude), alpha(b) is found to increase proportional to Fr and logarithmically with h(0k). The model has two free parameters that are determined from experiments and simulations. The augmentation of long wavelength perturbations by mode coupling is also evaluated. This is found to decrease the sensitivity of alpha(b) on the initial perturbations when they are smaller than the saturation amplitude of the most unstable modes. These results show that alpha(b) can vary by a factor of 2-3 with initial conditions in reasonable agreement with experiments and simulations.

Molecular-dynamics simulations of electron-ion temperature relaxation in a classical Coulomb plasma.

Molecular-dynamics simulations are used to investigate temperature relaxation between electrons and ions in a fully ionized, classical Coulomb plasma with minimal assumptions. Recombination is avoided by using like charges. The relaxation rate agrees with theory in the weak coupling limit (g identical with potential/kinetic energy << 1), whereas it saturates at g > 1 due to correlation effects. The "Coulomb log" is found to be independent of the ion charge (at constant g) and mass ratio > 25.

Nanohydrodynamics simulations: an atomistic view of the Rayleigh-Taylor instability.

Nanohydrodynamics simulations, hydrodynamics on the nanometer and nanosecond scale by molecular dynamics simulations for up to 100 million particles, are performed on the latest generation of supercomputers. Such simulations exhibit Rayleigh-Taylor instability, the mixing of a heavy fluid on top of a light in the presence of a gravitational field, initiated by thermal fluctuations at the interface, leading to the chaotic regime in the long-time evolution of the mixing process. The early-time behavior is in general agreement with linear analysis of continuum theory (Navier-Stokes), and the late-time behavior agrees quantitatively with experimental observations. Nanohydrodynamics provides insights into the turbulent mixing process that are inaccessible to either continuum calculations or to experiment.