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Despite improved clinical characterization, autoimmune pancreatitis is often still diagnosed only after a major operative procedure. This study seeks to elucidate the circumstances that contribute to an inaccurate preoperative diagnosis.Two independent reviewers identified retrospectively an institutional cohort of 68 patients with adequate clinical data to support the diagnosis of autoimmune pancreatitis. Further data regarding presentation, diagnostic studies, and clinical course was abstracted from medical records. Comparative analyses were performed between those patients who underwent major operative procedures and those who did not.Fifty-three patients underwent operative intervention as their initial treatment. Compared to the 15 patients avoiding operation, these patients were less likely to have diffuse pancreatic enlargement identified on pretreatment imaging (8% vs 80%) or to have pretreatment serum IgG4 level evaluations (11% vs 100%). Among the 21 patients in whom IgG4 levels were first checked postoperatively, only 12 had increases of at least twice the upper limit of normal. Pretreatment fine needle aspirates were interpreted incorrectly as definite or suspicious for adenocarcinoma in 12 patients, of whom 10 underwent operation. Clinically important postoperative disease recurrence was suspected or proven in 13 patients.Pitfalls leading to major pancreatic resections in autoimmune pancreatitis include unnecessarily high thresholds for initiating serum IgG4 evaluation, false positive cytologic evaluations for malignancy, and failure to recognize non-classic initial presentations, or recurrence of disease. Better diagnostic strategies are needed, but awareness of these specific findings should help to decrease the number of patients undergoing operation for unrecognized autoimmune pancreatitis.