title: Use of a standardized diagnostic approach improves the prognostic information of histopathologic factors in pancreatic and periampullary adenocarcinoma.
abstract: BACKGROUND
  Variability in reported histopathology parameters in operated periampullary adenocarcinomas may affect the prognostic weight of the parameters. Standardized axial sectioning produces a higher incidence of involved margins and also seems to produce a lower relative incidence of pancreatic compared with distal bile duct origin and a higher incidence of involved lymph nodes, compared with non-standardized procedure. The aims of this study were to 1) assess how a previously not described standardized pathology procedure, with longitudinal sectioning along the distal bile duct, affects reported tumour origin, margin status and involved lymph nodes, compared with non-standardized procedure, 2) assess if re-evaluation of microscopic slides affects the prognostic value of margin status and 3) compare the results of this standardized procedure with reported results of other standardized and non-standardized procedures.
  
  
  METHODS
  One hundred seventy-five consecutive pancreaticoduodenectomy specimens with primary adenocarcinomas, operated during 2001 - 2011 at the University hospitals of Lund and Malmö, Sweden, were re-evaluated histologically, and parameters relevant for classification and prognosis were assessed, with 1 mm as a threshold for involved or uninvolved margins. Follow-up lasted until 31 December 2013. Five-year overall survival (OS) and hazard ratios (HR) were calculated for the margin status stated in the original reports and margin status after re-evaluation.
  
  
  RESULTS
  Compared with non-standardized cases (n = 129), standardized cases (n = 46) had more involved lymph nodes in the specimens (median 3 vs 1), a higher fraction of distal bile duct origin (39% vs 21%) and a higher fraction of involved margins (74% vs 47%). The prognostic value of uninvolved margins increased by re-evaluation of slides (p < 0.001) and the adjusted HR for involved margins increased from 1.6 (95% CI 1.1 - 2.4) to 3.3 (95% CI 1.5 - 7.0). Uninvolved margins remained a significant predictor of OS in adjusted analysis.
  
  
  CONCLUSIONS
  Both the method of sectioning the specimen and the microscopic assessment affect prognostic pathology parameters significantly. The results of the herein described standardized method are similar to the results of other standardized procedures. The 1-mm threshold for involved margins in pancreaticoduodenectomies is relevant for OS, and margin status is an independent prognostic parameter.
  The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1056639379120615.
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund SE-221 85, Sweden. Jacob.Elebro@med.lu.se.
authors.forename: Jacob
authors.initials: J
authors.lastname: Elebro
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000368:Aged; D014670:Ampulla of Vater / Q000473:pathology* / Q000601:surgery; D003138:Common Bile Duct Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D006785:Hospitals, University; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008853:Microscopy / Q000592:standards; D008875:Middle Aged; D016577:Pancreaticoduodenectomy; D010338:Pathology, Clinical / Q000379:methods / Q000592:standards*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D013048:Specimen Handling / Q000592:standards; D013548:Sweden; D013997:Time Factors; D016896:Treatment Outcome
references.citation: Histopathology. 2008 Jun;52(7):787-96
references.pmid: 18081813
references.citation: HPB (Oxford). 2009 Feb;11(1):18-24
references.pmid: 19590619
references.citation: Ann Surg. 2008 Jul;248(1):97-103
references.pmid: 18580212
references.citation: Surgery. 2006 Nov;140(5):764-72
references.pmid: 17084719
references.citation: J Hepatobiliary Pancreat Surg. 2004;11(5):301-9
references.pmid: 15549428
references.citation: Arch Surg. 2004 Jul;139(7):718-25; discussion 725-7
references.pmid: 15249403
references.citation: BMC Cancer. 2008 Jun 11;8:170
references.pmid: 18547417
references.citation: Br J Surg. 2012 Aug;99(8):1036-49
references.pmid: 22517199
references.citation: BMC Cancer. 2008 Jan 14;8:5
references.pmid: 18194510
references.citation: Diagn Pathol. 2011 Oct 25;6:102
references.pmid: 22027009
references.citation: Br J Surg. 2006 Oct;93(10):1232-7
references.pmid: 16804874
references.citation: Surgery. 2012 Sep;152(3 Suppl 1):S103-11
references.pmid: 22766366
references.citation: Dig Surg. 2004;21(3):202-9
references.pmid: 15218236
references.citation: Eur J Surg Oncol. 2001 Sep;27(6):549-57
references.pmid: 11520088
references.citation: Cancer. 1995 Apr 15;75(8):2069-76
references.pmid: 7697596
references.citation: Ann Surg Oncol. 2010 Apr;17(4):991-7
references.pmid: 20108122
references.citation: Jpn J Cancer Res. 1994 Feb;85(2):161-6
references.pmid: 7511574