Pancreatic intraepithelial neoplasia arising from an ectopic pancreas in the small bowel

BACKGROUND： Ectopic pancreatic tissue is relatively uncommon, and is characterized as pancreatic tissue with no contact with the normal pancreas, and with its own ductal system and blood supply. It is usually asymptomatic, and can be incidentally diagnosed by conventional imaging studies. METHOD： A 69-year-old woman with a prior history of bilateral breast carcinoma presented with ectopic pancreatic intraepithelial neoplasia （PanIN） that was identified incidentally in the small bowel during an oncological resection of a synchronous primary pancreatic adenocarcinoma, and renal cell carcinoma. RESULTS： The patient underwent subtotal pancreatectomy with splenectomy, regional lymphadenectomy, radical left nephrectomy, and small bowel resection with primary anastomosis of ectopic PanlN-2. She had an uneventful hospitalization and was discharged home on postoperative day 7. CONCLUSIONS： The occurrence of ectopic PanIN is extremely unusual with only few cases previously reported in the literature. The need for negative margins after surgical resection of ectopic PanIN lesions remains controversial.

Mutations in the p16 gene in DMBA-induced pancreatic intraepithelial neoplasia and pancreatic cancer in rats

BACKGROUND：7,12-dimethylbenzanthracene（DMBA）-induced pancreatic intraepithelial neoplasia（PanIN）and pancreatic cancer in rats provide a classic model for uncovering the molecular mechanisms underlying pancreatic cancer.However,this model has not been characterized genetically,and in particular,the major genetic alterations in the p16 gene are unknown.METHODS： Lesions of PanlN and pancreatic cancer were induced with DMBA implantation in 40 rats, and control pancreatic tissue was obtained from 10 age-matched rats without exposure to DMBA. Pancreatic tissue was harvested three months after DMBA implantation and DNA was extracted. Homozy- gous deletions and point mutations of the pl6 （exons 1 and 2） gene were detected by PCR amplification and direct sequencing. RESULTS： DMBA implantation in the 40 rats induced 26 Pan- INs and 9 carcinomas. The overall frequency of p 16 alterations in the pancreatic tissue of these rats was 42.86% （15/35）, and the changes were point mutations, not homozygous deletions. p16 mutations were present in 30.77% （8/26） of the rats with PanIN and 77.78% （7/9） of the rats with carcinoma （P〈0.05）. The increasing incidence of p16 alterations was detected in 20.00% （1/5） of PanIN-1, 28.57% （2/7） of PanIN-2 and 35.71% （5/14） of PanIN-3 lesions. CONCLUSION： Our findings indicated that p16 alteration is a common event in the carcinogenesis of this model and that the mutation pattern is analogous to that of human lesions.

High-grade pancreatic intraepithelial lesions： prevalence and implications in pancreatic neoplasia

BACKGROUND： High-grade pancreatic intraepithelial neoplasia（Pan IN-3）, a precursor of pancreatic ductal adenocarcinoma（PDAC）, is not universally detected in resected pancreatic neoplasms. We sought to determine the prevalence and prognostic relevance of Pan IN-3 lesions in primary surgical resections of PDACs and intraductal papillary mucinous neoplasms（IPMNs）.METHODS： A retrospective review of a tertiary care center pathology database（1/2000-6/2014） was performed. Demographics, imaging, pathology, disease-recurrence, and survival data were reviewed.RESULTS： A total of 458 patients who underwent primary pancreatic resection were included. “Pan IN-3” lesions were found in 74（16.2%） patients who either had PDAC（n=67） or main duct（MD）-IPMN（n=7）. Among IPMN-MDs, Pan IN-3 lesions were exclusively found in those with pathological evidence of chronic pancreatitis. For PDACs, the median overall survival（OS） for pancreata with Pan IN-3 lesions was significantly better than those without（OS 1.12 years, interquartile range [IQR] 0.72, 2.05 years vs OS 0.86 years, IQR 0.64,1.60 years respectively; P=0.04）. Multivariate Cox regression analysis demonstrated that the presence of Pan IN-3 lesions was associated with a reduced risk of death（HR=0.43; 95% CI： 0.23-0.82; P=0.01）.CONCLUSIONS： Following primary resection of pancreatic adenocarcinoma, the lower survival observed in patients without Pan IN-3 lesions might suggest a state of complete or accelerated transformation. Further investigations are necessary to validate these findings that might impact disease prognosis and management.

Pancreatic ductal adenocarcinoma associated with pancreatic ductal intraepithelial neoplasia(The Author reply)

The Editor welcomes submissions for possible publication in the Letters to the Editor section that consist of commentary on an article published in the Journal or other relevant issues.

Pancreatic ductal adenocarcinoma associated with pancreatic ductal intraepithelial neoplasia

To the Editor:I read the report of Krishnasamy et al1 with great interest.The authors make a valid point about management issues associated with pancreatic ductal intraepithelial neoplasia (PanIN) in their illustrativereport.However,a few clarifications need to be made on surgical pathology aspect of these lesions. Without

Overexpression of catechol-O-methyltransferase occurs early in the progression of pancreatic cancer

Aims:Catechol-O-methyltransferase(COMT)plays a role in many kinds of cancer,and its high expression in pancreatic cancer has been found to be related to better prognosis.However,the expression and biological significance of COMT in multistep pancreatic cancerogenesis is not clear.Main methods:Six LSL-Kras^(G12D)-positive and Pdx1-Cre-positive mice(Kras^(G12D)mice),6 wild-type mice and 1 human tissue microarray were used in this study.COMT protein expression was measured by immunohistochemistry,and DNA chips were made for use in COMT mRNA assays.Keyfindings:The expression of COMT in pancreatic intraepithelial neoplasias(PanINs)from Kras^(G12D)mice was significantly higher than that in normal pancreatic tissue from wild-type mice,both in terms of protein level and mRNA expression.The median COMT immunohistochemistry expression scores in human PanIN-1 and PanIN-2 were 70 and 160,respectively,which were significantly lower than the score of 170 observed in pancreatic ductal adenocarcinoma(PDAC)(P=.024 and.037,respectively)and significantly higher than the score of 25 observed in pancreatitis(P=.01 and.008,respectively).Significance:In the development of pancreatic cancer from chronic pancreatitis and in the transition of PanIN to PDAC,we observed significantly increased expression of COMT.These data predict that the overexpression of COMT is an early event in the multistep process of pancreatic cancerogenesis.