In this episode, it is revealed that Bleeding Gums Murphy could be possibly related to Dr. Hibbert. He states, "All I had was a little brother who grew up to become a doctor. He used to laugh at the most inappropriate times." Hibbert then replies with, "Hey, I've got an older brother that I'll never see. He's a jazz musician, or some such."
This is the first episode to feature a Simpson getting an organ permanently extracted (in this case, Bart getting his appendix extracted due to appendicitis caused by eating a metal sharp Krusty-O).
Like in Treehouse of Horror V, a poison gas cloud was briefly seen in the ending (in this case, seeping into Chief Wiggum's car). However, the gas cloud does not turn him inside out, but rather suffocates him.
The music just before Bart's operation is a parody of the theme song of ER.
Bart showing off his appendectomy scar (which prompts a number of other children to want the operation) is reminiscent of the children's book Madeline: Madeline has her appendix out, says that her favorite thing about the experience is her scar, and the rest of the girls in her school want to have their appendixes out as well.
Both Steve Allen and Bill Cosby use Murphy's guest appearances as opportunities to make blatant product endorsements, while virtually ignoring Murphy himself. Cosby refers to his endorsements of New Coke, Jell-O Pudding and Kodak Film.