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To compare the efficacy of endoscopic retrograde cholangiopancreatography ± endoscopic sphincterotomy (ERCP ± ES) versus traditional conservative management in early gallstone pancreatitis with persistent ampullary obstruction (GSP + AO).The effectiveness of early ERCP ± ES in this setting is controversial.Sixty-one consecutive patients with GSP + AO within 48 hours from the onset of symptoms were randomized to receive either conservative treatment and selective ERCP ± ES after 48 hours (control group, 31 patients) or initial conservative treatment and systematic ERCP ± ES within 48 hours if obstruction persisted 24 hours or longer (study group, 30 patients). Patient outcome was compared in relation to treatment groups and to duration of obstruction.In the control group, 22 patients disobstructed spontaneously within 48 hours; 3 of the remaining 9 patients underwent ERCP ± ES and none had impacted stones. In the study group, 16 patients disobstructed spontaneously and 14 underwent ERCP within 48 hours from the onset of symptoms; impacted stones were found and extracted by ES in 79% (11 of 14) of these.There were no deaths in either group. Patients in the study group showed a shorter period of obstruction (P = 0.016) and a lower rate of immediate complications (P = 0.026) than controls. Patients with obstruction lasting ≤48 hours regardless of the treatment group had fewer immediate complications than those whose obstruction persisted longer (P < 0.001).This study shows that in patients with GSP + AO limiting the duration of obstruction to not longer than 48 hours by ERCP + ES decreased morbidity.