Pancreatic cancer invasion via neural routes (perineural invasion) has been studied extensively, but detailed research on the morphology of innervation of the pancreas related to perineural invasion is scarce. To clarify the morphology of neural distribution in the human pancreas. The pancreas and surrounding structures were dissected in 9 cadavers, the specimens were immersed in a 0.001% solution of alizarin red S in ethanol to stain the peripheral nerves, and the detailed distribution was studied to confirm the extrapancreatic and intrapancreatic plexus using a binocular microscope. The innervation of the uncinate process of the pancreas originated from the superior mesenteric plexus (SMPlx) along the inferior pancreaticoduodenal artery (IPDA), but did not form a wide offshoot of nerve bundles as reported. Concerning the innervation of the body and tail, it was found that the nerve fibers entered the pancreas immediately after leaving the celiac plexus, and were distributed around the pancreatic duct in a twig-like manner. It was emphasized that the nerve originating from SMPlx to the uncinate process chiefly ran along the IPDA and it was necessary to focus one's attention not only on the extrapancreatic perineural invasion but also on the intrapancreatic perineural invasion in carcinoma of the body and tail of the pancreas.

To clarify the innervation of human gallbladder, with special reference to morphological understanding of gallstone formation after gastrectomy. The liver, gallbladder and surrounding structures were immersed in a 10 mg/L solution of alizarin red S in ethanol to stain the peripheral nerves in cadavers (n=10). Innervation in the areas was completely dissected under a binocular microscope. Similarly, innervation in the same areas of 10 Suncus murinus (S. murinus) was examined employing whole mount immunohistochemistry. Innervation of the gallbladder occurred predominantly through two routes. One was from the anterior hepatic plexus, the innervation occurred along the cystic arteries and duct. Invariably this route passed through the hepatoduodenal ligament. The other route was from the posterior hepatic plexus, the innervation occurred along the cystic duct ventrally. This route also passed through the hepatoduodenal ligament dorsally. Similar results were obtained in S. murinus. The route from the anterior hepatic plexus via the cystic artery and/or duct is crucial for preserving gallbladder innervation. Lymph node dissection specifically in the hepatoduodenal ligament may affect the incidence of gallstones after gastrectomy. Furthermore, the route from the posterior hepatic plexus via the common bile duct and the cystic duct to the gallbladder should not be disregarded. Preservation of the plexus may attenuate the incidence of gallstone formation after gastrectomy.

Peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands inhibit the growth of PPAR-γ expressing cancer cells through terminal differentiation. However, there are few studies examining the effect of a PPAR-γ ligand on metastatic potential of cancer cells in an animal model and the underlying molecular mechanisms. We have recently developed a rectal cancer xenograft animal model in which anti-tumor and anti-metastatic efficacy of agents can be evaluated. This study was designed to examine whether a representative PPAR-γ ligand, thiazolidinedione (TZD), could inhibit growth and metastasis of PPAR-γ positive HT-29 human colon cancer cells through the induction of terminal differentiation. TZD caused G1 arrest in association with a marked increase in p21Waf-1, Drg-1, and E-cadherin expression. In untreated cancer cells, fluorescence immunostaining demonstrated β-catenin in the nucleus and/or cytoplasm; in TZD-treated cancer cells, β-catenin localization shifted to the plasma membrane, in association with increased E-cadherin at this site and reduced tyrosine phosphorylation of β-catenin. In addition, TZD completely inhibited lymph node and lung metastases in the xenograft animal model, and TZD inhibited growth of primary xenografts by 40%. These results suggest that TZD can function as a cytostatic anti-cancer agent to inhibit growth and metastasis of HT-29 colon cancer cells through differentiation-promoting effects. These effects involve not only modulation of the E-cadherin/β-catenin system, but also up-regulation of Drg-1 gene expression.