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R0 Versus R1 Resection Matters after Pancreaticoduodenectomy, and Less after Distal or Total Pancreatectomy for Pancreatic Cancer

Demir, Ihsan Ekin, MD, PhD*; Jäger, Carsten, MPH*; Schlitter, A. Melissa, MD; Konukiewitz, Björn, MD; Stecher, Lynne, PhD; Schorn, Stephan, MD*; Tieftrunk, Elke, MD*; Scheufele, Florian, MD*; Calavrezos, Lenika, MD*; Schirren, Rebekka, MD*; Esposito, Irene§; Weichert, Wilko; Friess, Helmut*; Ceyhan, Güralp O.*

doi: 10.1097/SLA.0000000000002345
ORIGINAL ARTICLES

Objective: The aim of this study was to decipher the true importance of R0 versus R1 resection for survival in pancreatic ductal adenocarcinoma (PDAC).

Summary of Background Data: PDAC is characterized by poor survival, even after curative resection. In many studies, R0 versus R1 does not result in different prognosis and does not affect the postoperative management.

Methods: Pubmed, Embase, and Cochrane databases were screened for prognostic studies on the association between resection status and survival. Hazard ratios (HRs) were pooled in a meta-analysis. Furthermore, our prospective database was retrospectively screened for curative PDAC resections according to inclusion criteria (n = 254 patients) between July 2007 and October 2014.

Results: In the meta-analysis, R1 was associated with a decreased overall survival [HR 1.45 (95% confidence interval, 95% CI 1.37–1.52)] and disease-free survival [HR 1.44 (1.30–1.59)] in PDAC when compared with R0. Importantly, this effect held true only for pancreatic head resection both in the meta-analysis [R0 ≥0 mm: HR 1.21 (1.05–1.39) vs R0 ≥1 mm: HR 1.66 (1.46–1.89)] and in our cohort (R0 ≥0 mm: 31.8 vs 14.5 months, P < 0.001; R0 ≥1 mm, 41.2 vs 16.8 months; P < 0.001). Moreover, R1 resections were associated with advanced tumor disease, that is, larger tumor size, lymph node metastases, and extended resections. Multivariable Cox proportional hazard model suggested G3, pN1, tumor size, and R1 (0 mm/1 mm) as independent predictors of overall survival.

Conclusion: Resection margin is not a valid prognostic marker in publications before 2010 due to heterogeneity of cohorts and lack of standardized histopathological examination. Within standardized pathology protocols, R-status’ prognostic validity may be primarily confined to pancreatic head cancers.

*Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

Institute for Pathology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

Institute for Medical Statistics and Epidemiology, Technical University of Munich, Munich, Germany

§Institute of Pathology, Heinrich Heine University, Düsseldorf, Germany.

Reprints: Güralp O. Ceyhan, MD, Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, D-81675 Munich, Germany. E-mail: gueralp.ceyhan@tum.de.

Ihsan Ekin Demir and Carsten Jäger contributed equally to this manuscript.

IED, CJ, HF, and GOC designed the study. IED and CJ performed the database search and extraction of articles. All authors contributed to the drafting of the manuscript. AMS, BK, IE, and WW performed the pathological analyses. SS, ET, RS, FS, LC critically revised the manuscript. LS critically assessed the statistical analysis and made corrections. All authors agreed on the submission of the manuscript.

The authors do not have any conflicts of interest.

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