I had a very similar problem. Every time I tried to create a new VM and needed to upload an ISO file, the datastore just disappeared. I personally believe this was due to my USB storage I was using just could not handle that write operation or was overheating or something like that. I added a second USB storage device and it all worked fine and has never gone down. ESXi is still running from the original USB storage though, it was a SanDisk mini 128GB thumb drive (the super small ones) Some USB storage is just not great I think.
I hope that helps? Sorry I did not keep any logs or anything like that to prove it out.