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The pope, whose expectations had been aroused, had to content himself with some additions to the duchy of Rome, and to the Exarchate of Ravenna, and the Pentapolis in the Marches, which consisted of the "five cities" on the Adriatic coast from Rimini to Ancona with the coastal plain as far as the mountains.
Adrian restored some of the ancient aqueducts of Rome, and rebuilt the church of Santa Maria in Cosmedin in Rome, decorated by Greek monks fleeing from the iconoclastal persecutions.
Adrian VI was in addition the only pope from The Netherlands as well as the last German pope until the 2005 papal conclave that elected Pope Benedict XVI.
Adrian was known for having attempted to launch a Catholic Reformation as a defense against the Protestant Reformation.
After the death of the latter, Adrian was appointed, on 14 March 1518, general of the reunited inquisitions of Castile and Aragon, in which capacity he acted until his departure for Rome on 4 August 1522 to assume his pontificate.