Histochemical studies on protein plugs obtained by endoscopic retrograde catheterization of the papilla

Abstract

In order to elucidate mechanisms of protein plug formation, histochemical studies were performed on aggregates and protein plugs present in pancreatic juice. Pancreatic juice was obtained from three control subjects and five patients with chronic pancreatitis through endoscopic retrograde catheterization of the papilla. Specimens for staining were prepared in two ways: (1) fixed with 10 per cent formaldehyde, embedded in paraffin and sectioned, and (2) placed on slide glass and fixed with isopropylalcohol. Staining included hematoxylin-eosin, periodic-acid Schiff, von Kossa, alcian blue, toluidine blue and double staining with PAS and AB. The process of protein plug formation can be as follows: (1) a prerequisite for aggregate formation, consisting of clusters of desquamated epithelial cells, highly concentrated sulfated acidic mucopolysaccharide and neutral mucopolysaccharide, (2) formation of aggregates in which epithelial cells and amorphous substance are interlaced with developing fine reticular substance, (3) enlargement of aggregates by fusion with adjacent aggregates through bridging action of the reticular substance sprouting, like prickles, from their surface, and (4) "maturity" of aggregates, taking a three-dimensional form which result in a spherical, spheroidal or cylindrical protein plug.

GP2, the homologue to the renal cast protein uromodulin, is a major component of intraductal plugs in chronic pancreatitis.

“…These findings are consistent with the structures identified as containing GP2 in our study. Furthermore, intraductal plugs observed in histological sections from patients with chronic pancreatitis are morphologically and histochemically similar to precipitates found in pancreatic juice collected by endoscopic cannulation of the pancreatic duct from these types of patients (8,18). This implies that in the setting ofchronic pancreatitis the aggregates we have described are intraductal plugs rather than nonspecific precipitates.…”

“…Previous studies have shown that the protein precipitates found in pancreatic juice collected by endoscopic cannulation of the pancreatic duct are similar to intraductal plugs seen in histological sections from patients with chronic pancreatitis. This is based on morphological appearance as well as histochemical findings (8,18). Since it is difficult to obtain surgical specimens that contain intraductal plugs, endoscopic cannulation of the pancreatic duct has made it possible to obtain pancreatic plugs floating within the juice.…”

“…Morphological and histochemical studies have suggested that pancreatic intraductal plugs arise by the interaction ofdesquamated epithelial cells with sulfated acidic mucopolysaccharides and glycoproteins (8,18). Through condensation and accumulation of a fine reticular substance, aggregates, which subsequently enlarge, form.…”

“…Glycoproteins and acidic mucopolysaccharides are also present in varying amounts (7,8). Morphologic analysis has demonstrated that plugs are initially formed by clusters ofdegenerating epithelial cells in a fine reticular meshwork, which then enlarge through the accretion of amorphous material to assume laminar structures (8).…”

“…Morphologic analysis has demonstrated that plugs are initially formed by clusters ofdegenerating epithelial cells in a fine reticular meshwork, which then enlarge through the accretion of amorphous material to assume laminar structures (8). Calcium deposits may subsequently appear on their surface leading to the formation of stones within the pancreatic duct system.…”