Inter Milan and Bayer Leverkusen cruised into the Europa League knockout stage with emphatic wins but holders Atletico Madrid and former winners Liverpool suffered surprise defeats.
Russia's Rubin Kazan, Olympique Lyon, Hanover 96 and Metalist Kharkiv joined Bayer and treble UEFA Cup winners Inter in sealing their progress to the last 32 with two games to spare.
Atletico Madrid's 16-match unbeaten run came to an end at Portugal's Academica, 2-0 winners thanks to a brace from Wilson Eduardo, while Ivorian striker Lacina Traore fired Russia's Anzhi Makhachkala to a 1-0 win over Liverpool in Moscow.
There was also a brilliant individual performance from Napoli striker Edinson Cavani, who scored four goals as the 1989 winners twice fought back from a goal down to beat Dnipro Dnipropetrovsk 4-2 and stay in the hunt.
Inter breezed past Serbian Champions Partizan Belgrade 3-1 in Serbia as Argentine forward Rodrigo Palacio came off the bench after a goalless first half and sent the Serie A side on their way with a brace.
Fredi Guarin added the third before Nemanja Tomic scored Partizan's first goal in the competition, which came as scant consolation after they suffered a fourth successive defeat and stretched their winless streak against Italian opposition to 24 years.
Inter coach Andrea Stramaccioni, who rested the bulk of his first-choice players who engineered a 3-1 win at Italian champions Juventus on Saturday, praised livewire Palacio after he silenced the noisy but well-behaved 25,000 home crowd.
"Palacio a very important player for us, he has very good skills because he is a versatile forward who can play in several positions and has an eye for goal," Stramaccioni told a news conference.
"We have continued our winning streak and this will give us the confidence we need to maintain our challenge for the Italian League title, starting with a difficult away game against Atalanta," he added.
Rubin booked their ticket with a 1-0 win at Azeri champions Neftchi Baku, while Bayer thrashed Rapid Vienna 3-0 and Metalist beat Rosenborg 3-1 to advance from Group K.
Lyon ensured their survival through the winter break with a 3-2 win at last season's runners-up Athletic Bilbao, who are out of the reckoning with just one point from four games, while Hannover edged Swedes Helsinborg at home by the same score thanks to an injury-time Szabolcs Huszti penalty.
Tottenham, who won the UEFA Cup in 1972 and 1984, kept alive their hopes of progressing with Jermain Defoe scoring a hat-trick in a 3-1 win over Slovenia's NK Maribor.
Former Bolton Wanderers player Fabrice Muamba walked on at halftime to salute the crowd in an emotional return for a player who nearly died at White Hart Lane in March when he suffered a cardiac arrest on the pitch.
With tears streaming down his face, he pointed to where he fell and then addressed the fans, who gave him a standing ovation.
Lazio top Group J with eight points after thrashing Panathinaikos 3-0, while Tottenham are second on six and Maribor slipped one place down to third on four points.
Fenerbahce also edged closer to the knockout stage with a 2-0 home win over AEL Limassol while 1976 winners Borussia Moenchengladbach are still deadlocked with Marseille after their 2-2 draw on the southern French coast.
Both sides have five points and are as many behind Fenerbahce after Gladbach striker Juan Arango first fired the German side into an early lead and then equalised in the 90th minute.
Swedish club AIK beat PSV Eindhoven in Stockholm thanks to a first-half wonder goal from on-loan Celtic striker Mohamed Bangura.
"If you're going to win these games, you have to score great goals. Mohamed scored a fantastic goal. A brilliant achievement," AIK coach Andreas Alm told Sweden's TV4 Sport.
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