According to the CDC, smoking can lead to Buerger's disease, which affects blood vessels in the arms and legs. Blood vessels swell, which can prevent blood flow, causing clots to form. This can lead to pain and tissue damage. Extreme cases can induce gangrene, which can require amputation. What statement best replaces the sentence, "Extreme cases can induce gangrene, which can necessitate amputation?"

Extreme cases can be caused by gangrene, which involves the removal of a limb.
Extreme cases can lead to gangrene, which can require removal of a limb.
Extreme cases can be caused by gangrene, which requires increased care.
Extreme cases can lead to gangrene, which involves involuntary care.