In my view, a significant aspect of a squeeze box, accordian, piano, etc., is that those are held or approached with symmetry. It then becomes just a matter of what each hand does, which is not a major problem. Living in a right-handed world, lefties tend to do quite a bit with their right hands anyway.

The difference with guitars, banjos, etc., is that they are held so that the arm positions are quite different. For many of us with a strong sense of our left-handedness, it's a very awkward feeling to hold an instrument in a right-handed position. Take a guitar, rifle, even a broom and reverse your arm positions as if you were left-handed and you'll likely get an idea of how unnatural it feels. I chose to play guitar left-handed not out of concern over what each hand was doing, but because holding a guitar right-handed felt totally wrong.