Only few spindle-shaped cells were found in the periacinar and interlobular areas in the normal pancreas. Fibrous elements were found in the ductal wall, periductal area and interlobular area.

Group 1: On day 3 after the last feeding of ethionine, mild proliferation of spindle cells staining for a-smooth muscle actin (a-SMA) was found in the periacinar and periductal areas (fig. 1). Under the electron microscope, zymogen granules, decreased in number and size, were found in acinar cells. On day 7, there was considerable fibrosis with proliferation of a-SMA positive cells (myofibroblasts) (fig. 2). On day 30, fibrous deposition had decreased, but mild fibrosis was focally found in the periductal and regenerated periacinar areas (fig. 3).

Group 2: Marked pancreatic atrophy and mild to moderate fibrosis in the periacinar, interlobular and peri-ductal areas was found.

Group 3: Marked pancreatic atrophy was found 2, 3 and 4 weeks after the last feeding (fig. 4a). The pancreas, showing normal macroscopic appearance and weight, was regenerated after 26 weeks (fig. 4b). Formation of fibrous connective tissues was most manifest 2 weeks after the last feeding. Fibrosis was found in the periductal and inter- and intra-lobular areas with destruction and b b

Fig. 2. Group 1. Day 7. a Proliferation of spindle shaped cells and collagen fibers in the periductal and intralobular areas. b Spindle shaped cells and capillary staining for a-SMA.

a loss of the exocrine parenchyma (fig. 5a). An increased staining of type III collagen and a lesser staining of type I collagen were found in all zones of fibrosis. Fibronectin was also found between the collagen bundles. Electron microscope findings showed fine collagen bundles in this area. Such fibrosis decreased thereafter and mild fibrosis was found in the periductal, perivascular and interlobular areas after 3 weeks (fig. 5b). Fibrosis had largely disappeared

Fig. 3. Group 1. Day 30. a Slight proliferation of spindle shaped cells in the periacinar and interlobular areas of the regenerated pancreas. b Slight proliferation of a-SMA positive spindle cells.

after 26 weeks. Pancreas lobules were almost regenerated, but focally remodelled with aggregated pancreatic ductules. Mild fibrosis was found only in these periductules and focally in interlobular areas after 26 weeks (fig. 6a, b). Slight proliferation of a-SMA positive cells (myofibroblasts) was found in these areas (fig. 7a, b) [11].

Fig. 4. Group 3. a Week 4. Marked atrophy of the pancreas. b Week 26. Regenerated pancreas showing almost normal macroscopic appearance.

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