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Autoimmune pancreatitis (AIP) is a mass forming inflammatory pancreatobiliary-centric disease. Recent reports of multiorgan inflammatory mass forming lesions with increased numbers of IgG4 positive plasma cells suggest that AIP may have a systemic component. In this study, we explore the systemic nature of AIP, investigate the relevance of subtyping AIP, perform a systematic study of tissue IgG4 immunoperoxidase, and ultrastructurally evaluate the presence of immune complexes. Our study group consisted of 36 patients with AIP, 21 of whom underwent a Whipple procedure. On the basis of the pattern of inflammation, pancreatic involvement was subtyped as ductocentric (AIP-D) or lobulocentric (AIP-L). Extrapancreatic lesions included bile duct (n=3), salivary glands (n=3), lung (n=2), gallbladder (n=11), and kidney (n=4). Clinical and radiologic data was recorded. Immunohistochemistry for IgG4 was performed on both pancreatic and extrapancreatic tissues and the numbers of IgG4 positive plasma cells were semiquantitatively scored. A control cohort composed of pancreatic adenocarcinoma (n=19) and chronic pancreatitis-not otherwise specified (NOS) (n=14) was also evaluated. Eleven pancreatic specimens, including 2 cases of chronic pancreatitis-NOS and 4 kidneys were evaluated ultrastructurally. The pancreas, bile duct, gall bladder, salivary gland, kidney, and lung lesions were characterized by dense lymphoplasmacytic infiltrates with reactive fibroblasts and venulitis. IgG4 positive plasma cells were identified in all pancreatic and extrapancreatic lesions. The AIP cases showed significantly more pancreatic IgG4 positive plasma cells than chronic pancreatitis-NOS or adenocarcinoma (P=0.001). However, IgG4 positive cells were identified in 57.1% of chronic pancreatitis-NOS and 47.4% of ductal adenocarcinoma. Fifteen of 21 resected cases were classified as AIP-D, and 6 as AIP-L, the latter notably showing significantly more IgG4 positive plasma cells than the former (P=0.02). Additionally, clinical and radiologic differences emerged between the 2 groups. Ultrastructurally, electron dense deposits of immune complexes were identified in the basement membranes of 7 of the 9 AIP cases and in 3 of the 4 renal biopsies evaluated. AIP represents the pancreatic manifestation of a systemic autoimmune disease. Clinical and immunologic findings justify the recognition of pancreatic lobulocentric and ductocentric subtypes. Documentation of increased numbers of tissue IgG4 positive plasma cells, although not an entirely specific marker for AIP, may provide ancillary evidence for the diagnosis of a IgG4-related systemic disease.

Although daptomycin is a well-tolerated antibacterial agent, clinicians should consider periodic monitoring of liver function and renal function tests to identify potential adverse effects.

Despite the widespread interest in this technology, there are a lot of shortcomings: limitations in equipment, lack of clinical outcome data, and absence of randomized trials that compare it with alternative conventional surgical interventions. Nevertheless, it is crucial to remember that we have just started the evaluation process for this new exiting technology, and that, clearly, the best is yet to come.

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