Eliminating the breast cancer surgery paradigm after neoadjuvant systemic therapy: current evidence and future challenges.

In patients with operable early breast cancer, neoadjuvant systemic treatment (NST) is a standard approach. Indications have expanded from downstaging of locally advanced breast cancer to facilitate breast conservation, to in vivo drug-sensitivity testing. The pattern of response to NST is used to tailor systemic and locoregional treatment, that is, to escalate treatment in nonresponders and de-escalate treatment in responders. Here we discuss four questions that guide our current thinking about 'response-adjusted' surgery of the breast after NST. (i) What critical diagnostic outcome measures should be used when analyzing diagnostic tools to identify patients with pathologic complete response (pCR) after NST? (ii) How can we assess response with the least morbidity and best accuracy possible? (iii) What oncological consequences may ensue if we rely on a nonsurgical-generated diagnosis of, for example, minimally invasive biopsy proven pCR, knowing that we may miss minimal residual disease in some cases? (iv) How should we design clinical trials on de-escalation of surgical treatment after NST?

Aortic regurgitant flow by color Doppler measurement of the local velocity 7 mm above the leak orifice--Part 1: in vitro measurements.

AIMS: The flow convergence method enables the determination of flow across restrictive orifices. It was validated for planar orifice plates and atrioventricular valves. However, its quantitative application to aortic regurgitation is complicated due to the complex valve anatomy which distorts the converging flow field. An open angle formed by the leaflets causes relatively lower velocities in the region near the orifice, resulting in underestimation of flow. Confinement of the flow convergence region by the ascending aorta relatively increases the velocities at greater distance to the orifice and can cause overestimation of flow. We hypothesized that there is a region at intermediate distance to the orifice, where both these effects on the flow field are minimal, so that the local velocity there is only a function of flow. METHODS AND RESULTS: In a flow model, aortic regurgitation was simulated. The flow convergence was imaged by color Doppler. Different scanning directions were used (analogue to apical and parasternal approach). Velocity profiles across the flow convergence were read along the line from the scanhead to the orifice. At a distance of 7 mm to the orifice, a uniform value was found for the ratio of local velocity v(7 mm)/flow (=0.28 cm(-2)). Variations in size (3.5 to 7 mm), site (central versus lateral) and leaflet angle (planar versus inverted funnel) of the orifice and in the scanning approach had only a minimal effect on this value. CONCLUSION: The aortic regurgitant flow convergence is characterized by a relatively uniform V (7 mm)/Q. Independent of variations in the anatomy and the scanning approach, this value directly reflects flow.

Influence of pulse repetition frequency and high pass filter on color Doppler maps of converging flow in vitro.

Assessment of regurgitant flow by the flow convergence method is based on reading absolute velocities from color Doppler maps. Velocity overestimation by high pass filtering above 100 Hz has been reported. An extremely low filter, however, is impracticable in patients. A ratio of pulse repetition frequency (PRF)/filter of 10/1 usually results in good quality color maps as judged visually. We studied in vitro the influence of RPF and filter on the absolute velocities within color maps of the flow convergence, keeping PRF/filter at 10/1. The color maps were also compared with computerized flow simulations. Flow across different orifice plates was scanned using two different setups for each flow condition: low velocity setup (PRF 600-2500 Hz, filter 50-300 Hz) and high (PRF 1500-6000 Hz, filter 200-600 Hz). From the color maps, velocity profile curves were read along the flow center line across the flow convergence. The high velocity setup provided artefact-free color maps at a distance d = 2-4 through 8-11 mm to the orifice, the low setup at d = 6-8 through 18 mm. Within the overlapping range (d = 6-8 through 8-11 mm), the resulting curves showed no significant differences in local velocity, with a slight trend towards higher velocities with the high velocity setup (2.2-2.9%). The simulations agreed well with color Doppler except for slightly lower values at d > 10-12 mm. Changes in PRF and filter have no significant influence on the absolute velocities displayed within color maps as long as PRF/filter is kept close to 10/1.

[Color Doppler echocardiography of the flow convergence region in vitro: effect of the orifice shape on proximal velocity profile]. / Farbdoppler-Echokardiographie der Flusskonvergenzregion in vitro: Einfluss der Lochform auf das proximale Geschwindigkeitsprofil.

The flow convergence method serves to determine flow across orifices (like valve leaks) by color Doppler. Both the PISA method (proximal isovelocity surface areas) and the PVP method (proximal velocity profile) were developed in vitro at circular orifice plates. Therefore, we studied the influence of a non-circular orifice shape on the color map of the flow convergence. Steady flow across orifices of the following shapes was imaged by color Doppler: Oval (6 x 2 mm), slit (12 x 1.5 mm), three-star (diameter 100, area 30 mm2), circular twin-orifice (two circular orifices diameter 2 mm at 10 mm distance from each other) and oval twin-orifice (two ovals 6 x 2 mm at 10 mm distance). As reference we imaged circular orifices with a similar opening area. The alias method was used to locate discrete velocities within the color map, and the proximal velocity profile along the flow center line was analyzed (mean of 24 subsequent images). The local velocity was plotted (y-axis) against its distance to the orifice (x-axis) providing proximal velocity profile curves. The more the orifice shape differed from circular, the more the proximal velocity profile was shifted downward: The profile proximal to the oval was not different from the reference profile proximal to the circular orifice. The profile proximal to the slit was considerably slowed, and proximal to the three-star was even slightly slower (local velocity -12 %, -23 % and -29 % at 14, 8 and 5 mm distance to the orifice). If the circular reference orifice corresponded to total flow across the twin-orifice, the proximal velocity profile of the latter was also shifted markedly downward (-20 %, -18 % and -23 % at 14, 8 and 5 mm distance to the circular twin-orifice). However, if the reference profile corresponded to flow across only one opening of the twin-orifice, the proximal velocity profile of the latter was shifted considerably upwards (+60 %, +71 % and +50 % at 14, 8, and 5 mm distance). Deviation of the orifice shape from circular leads to lower local velocities within the flow convergence; thus neglecting this orifice shape would result in underestimation of flow by the flow convergence method. However, presence of parallel neighboring flow increases the local velocities; neglecting this effect would lead to corresponding overestimation of flow.