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It was stated by the original poster that his wife has a study permit and multiple entry visa good for the next three years. The only circumstance where I could see her definitely not being allowed back in would be where they determined she is not actually enrolled in and attending a school. Yes, she could be denied entry, but if she is a legitimate student then I would say the chances of being denied entry are minimal.
 
In-land you are not allowed to leave, that's why it's called inland.
If you wanna go for the weekend somewhere on vacation or whatever, apply outland.
 
Taken from the CIC Help centre:

Can I go on vacation while my application for permanent residence is being processed?

Taking a vacation outside of Canada should not affect your application for permanent residence. However, if you leave Canada while your application is being processed, you may not be allowed to come back into Canada. Each time you come back, you must meet all the rules for entering the country.

If you leave Canada and want to return, you must have:

a valid passport or other travel documents;
a valid work permit, if you are returning to work in Canada; and
a valid temporary resident visa, if you are a citizen of a country for which Canada requires one.