This is, to our best knowledge, the first report on standardized longitudinal opening and slicing of the common bile duct in the handling of PD-specimens with primary adenocarcinoma.
Our results confirm previous reports on standardized protocols in the pathology examination of operated periampullary adenocarcinomas by showing that a 1-mm cut-off in the assessment of margin status is relevant for overall survival, both in unadjusted analysis and after adjusting for other histopathology parameters. Microscopic re-evaluation of margin status revealed a larger proportion of involved margins than stated in the original reports. Thereby, the prognostic value of uninvolved margins was increased, regardless of other histopathology parameters. This suggests that a “guilty until proven innocent”-approach towards margins in pancreaticoduodenectomies gives more accurate prognostic information than the opposite approach. Moreover, survival in the large group of cases with unassessable margin status (Rx) differed significantly both from cases with uninvolved margins and from cases with involved margins, suggesting that it is not appropriate to classify these cases as R0.
The more frequent finding of growth in peripancreatic fat and perineural tumour growth in SP-cases compared to NSP-cases may be an effect of more extensive sampling in the periphery of the tumour as well as along the bile duct and margins in SP-cases compared with NSP-cases.
Tumour infiltration in blood vessels was more often found in NSP-cases than in SP-cases (29% vs 9%), which may be due to an unintended more thorough search for evaluable pathology parameters in SP-cases that had very little coverage on margins and lymph nodes. This model of explanation suggests that the proportion of cases with tumour infiltration in blood vessels in the NSP-group more accurately reflects the actual percentage of infiltration in blood vessels. As a cautionary remark, the possibility of a type I error, i.e. a false positive detection of significant differences between the NSP-group and the SP-group, should also be considered, since a large number of comparisons have been performed. A type II error, i.e. failure to detect the true incidence of involved blood vessels in the SP-group, is also possible due to the relatively small sample size in this group.
Comparisons of the incidence of involved margins between our SP-material, excluding duodenal origin, and other standardized series show 78% R1 (32/41) in our SP-group compared with 59% (32/54) and 61% (51/83) in the LEEPP-series [2, 3]. The incidence of involved margins is often not comparable between SP-series and NSP-series, due to a 0-mm definition of margin involvement, or lack of definitions on margin involvement in NSP-series. The fraction of cases with involved lymph nodes is however comparable, showing that non-standardized series [4–10] report involved lymph nodes in less than 60% of cases, compared to more than 70% in our SP-group and in the LEEPP-series. If such differences are coincidental or actually statistically significant, as well as their potential clinical significance, remains unknown. In the present study, we were able to demonstrate a significantly higher number of involved lymph nodes in the specimens in the SP-group compared with the NSP-group, despite a temporal association between an increased number of lymph nodes harvested from the specimens by the surgeons and the studied standardized protocol.
In our material the differences in tumour origin between the SP-group and the NSP-group were significant. It is however not known if there are any clinically relevant differences between the tumour origins of standardized and non-standardized series. It has however previous been shown that the morphological distinction between intestinal and pancreatobiliary morphology has prognostic implications, not only in ampullary adenocarcinomas, but in all periampullary adenocarcinomas, regardless of tumour origin . Moreover, while differences in the expression of cytokeratins and mucins according to morphology have been observed in ampullary carcinomas , these differences seem to be less evident in series stratified solely by the anatomical centre of the ampullary adenocarcinomas . These findings suggest that morphological and molecular tumour characteristics have a greater prognostic impact than the appreciated tumour origin.
Despite a very different approach to the specimen, the results on tumour origin, N-stage and margin status in our standardized group are similar to the results of the LEEPP-series [2, 3] and to a lesser degree similar to the results of two other variants on standardized protocols [17, 18]. Whether or not our standardized protocol was more time consuming or more demanding than the LEEPP, and thus inferior due to practical reasons, has however not been studied.