To determine problems involved in the treatment and diagnosis of pancreatic cancer, a collective study of small carcinoma of the pancreas (2 cm or less in diameter) was performed. One hundred six cases were collected and analyzed. The results were as follows: In small carcinoma of the pancreas, the resectability rate was 99.0% and the operative mortality rate was 4%. Only 44% of the patients belonged to Stage I, and 14% belonged to Stage III or IV. Lymph node involvement, capsular invasion, retroperitoneal invasion, and vascular invasion were found in 30, 20, 12, and 9% of the patients, respectively. The postoperative cumulative 5-year survival rate was 30.3%, and that of Stage I was 37.0%. A small-sized tumor of the pancreas is not always an early carcinoma, but a tumor in Stage I may be regarded as an early carcinoma. Percutaneous transhepatic cholangiography and endoscopic retrograde cholangiopancreatography were the main diagnostic indicators in cases with and without jaundice, respectively. There was no specific single serum test for detecting small pancreatic cancer.

Key Points Ezh2 loss in hematopoietic stem cells predisposes mice to develop heterogeneous hematologic malignancies. Ezh1 is essential to maintain hematopoiesis in the setting of Ezh2 loss.

Loss of Ezh2 in the presence of activating mutation in JAK2 (JAK2V617F) cooperatively alters transcriptional programs of hematopoiesis, activates specific oncogenes, and promotes the development of myelofibrosis.

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SUMMARYWe have recently reported the accumulation of oligoclonal activated T cells in the spontaneously developed autoimmune pancreatitis in aly/aly mouse. In this study, we examined the effects of FK506 in this mouse model in preventing autoimmune pancreatitis and investigated its action on calcium signalling apoptosis of alymphoplasia (aly) lymphocytes in vitro. Mice were treated with FK506 from 8 to 25 weeks of age. At the age of 15 weeks, minimal mononuclear cell infiltration was observed in the pancreas in both the FK506 treated group and the control group. Furthermore, a marked cell infiltration associated with destruction of acini and partial fatty changes were observed in 25-week-old control mice. In contrast, FK506 treated mice showed almost no tissue destruction or mononuclear cell infiltration at the age of 25 weeks. Furthermore, at 15 weeks of age, most mononuclear cells in FK506-treated mice were TUNEL positive, whereas only a few were positive in control mice. This augmentation of T cell apoptosis by FK506 was confirmed using naive splenocytes activated by PMA and ionomycin in vitro. Finally, a suppressive effect of FK506 on Bcl-2 production but not on Bax production was confirmed by Western blotting. This unique effect of FK506 on the augmentation of T cell apoptosis is probably one of the mechanisms explaining its beneficial effect on aly autoimmune pancreatitis.

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The methods we used to produce a carcinoma in the extrahepatic bile duct and gallbladder in hamsters are described along with the characteristics of the induced tumors. Female Syrian golden hamsters were first subjected to Cholecystoduodenostomy with dissection of the extrahepatic bile duct on the distal end of the common duct (CDDB) and were, 4 weeks later, treated with weekly subcutaneous injections of N‐nitrosobis(2‐oxopropyl)amine (BOP) at a dose of 10 mg/kg body weight for 9 weeks. The animals were killed at the 12th, 16th and 20th week after the initiation of BOP treatment. Extrahepatic bile duct carcinoma developed in 16%, 24% and 41% and gallbladder carcinoma occurred in 58%, 81% and 82% of the hamsters, respectively, at the corresponding times of killing. The incidences were significantly higher than those in sham‐operated controls (P<0.01). The induced extrahepatic bile duct carcinomas were predominantly of the polypoid type and gallbladder carcinomas were of the papillary type in growth form, being morphologically similar to early stage biliary carcinoma in humans. Immunohistochemical staining using bromodeoxynridine and anti‐bromo‐deoxyuridine monoclonal antibody demonstrated that the CDDB procedure greatly accelerated the cell kinetic activity of the biliary epithelium, and this was considered to be a major factor promoting the development of biliary carcinomas in this hamster model. In conclusion, this new model provides a high incidence of tumor development at the extrahepatic biliary tract and is expected to be useful for clarifying the characteristics of this highly malignant tumor.

Six patients with adenosquamous carcinoma (ASqC) of the pancreas were studied clinicopathologically and immunohistochemically. In five of six ASqC tumors, both malignant squamous and glandular elements were reactive with CA 19-9, ST 439, and keratin antibodies. In contrast, a portion of the glandular element in the remaining one ASqC was reactive with CA 19-9 and ST 439 antibodies, but that of the squamous cell carcinoma (SqCC) was not reactive. However, SqCC of this tumor was intensely reactive with keratin antibody. These immunohistochemical results suggest that the histogenesis in one ASqC tumor was different from that of the other 5 ASqCs, and that this tumor may be a collision tumor rather than transformation to SqCC from adenocarcinoma, which is a very rare pattern of histogenesis in ASqC. The patients with ASqC of the pancreas showed shorter survivals following operations because of systemic metastasis including liver metastasis.