Different surgical tools are required for different operations and injuries players may need to drain blood pools obstructing the operating area, use a surgical laser to treat small tumors or boils, forceps to close wounds, and sutures to sew up both wounds and incisions.

Operations range from treating surface wounds and extraction operations-carried over from the original-to new operations including organ transplants and repairing broken bones. Surgery takes place from a first-person view. Missions can be played on different difficulty settings. Each operation tasks players with curing the patient of their ailment within a time limit. The two are surgeons with a mystical ability called the Healing Touch. Players take on the roles of original protagonist Derek Stiles and new character Naomi Kimishima. Second Opinion is a remake of Trauma Center: Under the Knife for the Nintendo DS. Trauma Center: Second Opinion is a video game that combines surgical simulation gameplay with storytelling using non-interactive visual novel segments using static scenes, character portraits, text boxes, and rare voice clips during gameplay segments. It was also a commercial success, selling over 400,000 units overseas. The game was positively reviewed by journalists, who praised its implementation of the Wii control scheme. The localization was done by Atlus USA, who focused on tightening the original script and merging it with the new narrative. The character Naomi was added to help set the game apart from the Nintendo DS original. Production was stressful due to a small team and tight development period. The game began development in early 2006. Gameplay combines surgical simulation with a story told as a visual novel, with operations and control options reworked for the Wii hardware.

Second Opinion expands on the original narrative through the perspective of Naomi Kimishima, another doctor with the Healing Touch. Set in a near future where medical science can cure previously incurable diseases, the story follows young surgeon Derek Stiles as he uses his mystical 'Healing Touch' to treat a new disease dubbed GUILT. The game was released in North America and Japan in 2006 by Atlus as a console launch title, and in other regions in 2007 by Nintendo. The second entry in the Trauma Center series, Second Opinion is a remake of the Nintendo DS title Trauma Center: Under the Knife (2005). Trauma Center: Second Opinion is a simulation video game developed by Atlus for the Wii.

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