I've had success with Sysinternals Process Explorer. With this, you can search to find what process(es) have a file open, and you can use it to close the handle(s) if you want. Of course, it is safer to close the whole process. Exercise caution and judgement.
To find a specific file, use the menu option Find->Find Handle or DLL... Type in part of the path to the file. The list of processes will appear below.
If you prefer command line, Sysinternals suite includes command line tool Handle, that lists open handles.
Examples
c:\Program Files\SysinternalsSuite>handle.exe |findstr /i "e:\" (finds all files opened from drive e:\"
c:\Program Files\SysinternalsSuite>handle.exe |findstr /i "file-or-path-in-question"