The number of lymph nodes identified in a simple pancreatoduodenectomy specimen: comparison of conventional vs orange-peeling approach in pathologic assessment.

Lymph node status is one of the most important predictors of survival in resectable pancreatic ductal adenocarcinoma; therefore, thorough lymph node evaluation is a critical assessment in pancreatoduodenectomy specimens. There is considerable variability in pancreatoduodenectomy specimens processed histologically. This study compares two approaches of lymph node dissection and evaluation (standard vs orange peeling) of pancreatoduodenectomy specimens. A different approach to dissection of pancreatoduodenectomy specimens was designed to optimize lymph node harvesting: All peripancreatic soft tissues were removed in an orange-peeling manner before further dissection of the pancreatic head. This approach was applied to 52 consecutive pancreatoduodenectomy specimens performed for ductal adenocarcinoma at two institutions. Specimen dissection was otherwise performed routinely. Overall number of lymph nodes harvested, number of positive lymph nodes, and their anatomic distribution were analyzed and compared with cases that had been dissected by the conventional approach. The mean number of lymph nodes identified by the orange-peeling approach was 14.1 (by institution, 13.8 and 14.4), as opposed to 6.1 (by institution, 7 and 5.3) in cases processed by conventional approach (P=0.0001). The number of lymph node-positive cases also increased substantially from 50% (by institution, 54 and 46%) in the conventional method to 73% (by institution, 88 and 58%) in the orange-peeling method (P=0.02). The orange-peeling method of lymph node harvest in pancreatoduodenectomy specimens for ductal adenocarcinoma enhances overall and positive lymph node yield and optimizes ductal adenocarcinoma staging. Therefore, lymph node harvest by the orange-peeling method should be performed routinely before specimen sectioning in assessment of pancreatoduodenectomy for ductal adenocarcinoma.

Characterization of pancreatic lesions from MT-tgf alpha, Ela-myc and MT-tgf alpha/Ela-myc single and double transgenic mice.

In order to identify good animal models for investigating therapeutic and preventive strategies for pancreatic cancer, we analyzed pancreatic lesions from several transgenic models and made a series of novel findings. Female MT-tgf alpha mice of the MT100 line developed pancreatic proliferation, acinar-ductal metaplasia, multilocular cystic neoplasms, ductal adenocarcinomas and prominent fibrosis, while the lesions in males were less severe. MT-tgf alpha-ES transgenic lines of both sexes developed slowly progressing lesions that were similar to what was seen in MT100 males. In both MT100 and MT-tgf alpha-ES lines, TGF alpha transgene was expressed mainly in proliferating ductal cells. Ela-myc transgenic mice with a mixed C57BL/6, SJL and FVB genetic background developed pancreatic tumors at 2-7 months of age, and half of the tumors were ductal adenocarcinomas, similar to what was reported originally by Sandgren et al 1. However, in 20% of the mice, the tumors metastasized to the liver. MT100/Ela-myc and MT-tgf alpha-ES/Ela-myc double transgenic mice developed not only acinar carcinomas and mixed carcinomas as previously reported but also various ductal-originated lesions, including multilocular cystic neoplasms and ductal adenocarcinomas. The double transgenic tumors were more malignant and metastasized to the liver at a higher frequency (33%) compared with the Ela-myc tumors. Sequencing of the coding region of p16ink4, k-ras and Rb cDNA in small numbers of pancreatic tumors did not identify mutations. The short latency for tumor development, the variety of tumor morphology and the liver metastases seen in Ela-myc and MT-tgf alpha/Ela-myc mice make these animals good models for investigating new therapeutic and preventive strategies for pancreatic cancer.

DeltaNp63 expression in pancreas and pancreatic neoplasia.

DeltaNp63 (DNp63) has become widely used, in particular, for distinguishing invasive carcinomas from noninvasive ducts by highlighting the myoepithelial or basal cells in the breast and prostate, respectively. It is not known whether this marker may have any application in another exocrine organ, the pancreas. As the ductal and intraductal proliferations of this organ become better characterized, the need for markers to distinguish among these processes increases. We investigated immunohistochemical expression of DNP63 in 105 cases. A total of 25 cases were non-neoplastic pancreata, 25 were pancreatic intraepithelial neoplasia (PanIN) of various grades, and 50 were examples of pancreatic ductal adenocarcinoma. Sections of non-neoplastic pancreata included various types of non-neoplastic processes such as squamous/transitional metaplasia (five cases), which can be mistaken for high-grade PanINs, as well as various degrees of reactive ductal atypia and incidental microcysts with attenuated lining (five cases). No DNp63 expression was noted in normal pancreatic ducts. On the other hand, all five foci of squamous/transitional metaplasia were strongly and uniformly positive for this marker. DNp63 labeling was also noted in those incidental microcysts lined by attenuated cells, seen amidst normal pancreatic lobules. All PanINs were negative. Among invasive carcinomas, DNp63 expression was detected only in areas of squamous differentiation and was completely absent in ordinary ductal areas. Based on this observation, five additional cases of adenosquamous/squamous carcinoma was retrieved and stained, and the squamous components of all of these were also positive. In conclusion, (I) DNp63 is a reliable marker of squamous differentiation in the pancreas. It is valuable in distinguishing squamous/transitional metaplasia from PanINs, a distinction of importance for both researchers and diagnosticians. Among invasive carcinomas, it seems to be entirely specific for areas of squamous differentiation. (II) Those incidental microcysts seen in acinar lobules and lined by attenuated cells are also positive for DNp63, which suggests that they may be metaplastic in nature, and that they do not represent neoplastic cells. (III) Unlike the ducts of other exocrine organs, breast and prostate, there are no DNp63-expressing cells in the normal pancreatic ducts, and therefore, this marker cannot be used in distinguishing invasive carcinomas from the non-invasive ducts. (IV) No p63-expressing 'stem' cells are present in the pancreas.