Prognostic Impact of Resection Margin Status in Distal Pancreatectomy for Ductal Adenocarcinoma

Abstract

Background Resection margin status is considered one of the few surgeon-controlled parameters affecting prognosis in pancreatic ductal adenocarcinoma (PDAC). While studies mostly focus on resection margins in pancreatoduodenectomy, little is known about their role in distal pancreatectomy (DP). This study aimed to investigate resection margins in DP for PDAC. Methods Patients who underwent DP for PDAC between October 2004 and February 2020 were included (n = 124). Resection margins and associated parameters were studied in two consecutive time periods during which different pathology examination protocols were used: non-standardized (period 1: 2004–2014) and standardized (period 2: 2015–2020). Microscopic margin involvement (R1) was defined as ≤1 mm clearance. Results Laparoscopic and open resections were performed in 117 (94.4%) and 7 (5.6%) patients, respectively. The R1 rate for the entire cohort was 73.4%, increasing from 60.4% in period 1 to 83.1% in period 2 (p = 0.005). A significantly higher R1 rate was observed for the posterior margin (35.8 vs. 70.4%, p < 0.001) and anterior pancreatic surface (based on a 0 mm clearance; 18.9 vs. 35.4%, p = 0.045). Pathology examination period, poorly differentiated PDAC, and vascular invasion were associated with R1 in the multivariable model. Extended DP, positive anterior pancreatic surface, lymph node ratio, perineural invasion, and adjuvant chemotherapy, but not R1, were significant prognostic factors for overall survival in the entire cohort. Conclusions Pathology examination is a key determinant of resection margin status following DP for PDAC. A high R1 rate is to be expected when pathology examination is meticulous and standardized. Involvement of the anterior pancreatic surface affects prognosis.

Prognostic Impact of Resection Margin Status on Distal Pancreatectomy for Ductal Adenocarcinoma

“…While it is well established that the gross pathology examination is a key determinant of the accuracy of margin status reporting for pancreatoduodenectomy specimens with PDAC [ 3 ], only a single study has investigated this important quality issue for distal pancreatectomy specimens. Sahakyan et al reported that the R1 rate increased from 60.4% to 83.1% following the implementation of a detailed pathology protocol that included a comprehensive, standardized grossing procedure for distal pancreatectomy specimens [ 7 ]. Specimen grossing consists of three steps: specimen dissection, macroscopic examination, and tissue sampling, and the latter in particular is a key determinant of the accuracy of margin assessment.…”

“…In the case of extended surgical procedures, the grossing technique employed is likely highly variable between centres and individual pathologists. Extended, multivisceral resection may be required if PDAC in the pancreatic body and tail infiltrates neighbouring organs and structures ( Table 1 ) [ 7 , 16 , 17 , 18 , 19 , 20 , 21 ]. While dissection of these complex specimens may be challenging, no guidance is provided by the main professional bodies.…”

“…In the studies by Sahakyan [ 7 , 33 ], Paye [ 18 ], Chang [ 23 ], and Shimada [ 35 ] and colleagues, the overall resection margin status was not a prognostic factor for survival in patients undergoing distal pancreatectomy for PDAC. Based on a meta-analysis combined with the analysis of a small institutional series, Demir and colleagues reported that margin status correlated with outcome in patients following pancreatoduodenectomy but not in the small subgroup of patients that had undergone distal pancreatectomy [ 32 ].…”

“…For one, the majority of patients with PDAC already have lymph node metastasis, perineural, and/or vascular invasion at the time of surgery, which may lead to disseminated disease and death before residual disease at the resection site becomes clinically manifest. For instance, in the study by Sahakyan and colleagues, R1 was a significant prognostic factor for survival in univariable analysis, but did not reach significance as an independent predictor for survival in multivariable analysis, unlike lymph node ratio and perineural invasion [ 7 ]. Similarly, others reported that lymph node status and perineural invasion were stronger determinants of outcome in PDAC than R-status [ 36 , 37 ].…”

ASO Author Reflections: Resection Margins in Distal Pancreatectomy for Ductal Adenocarcinoma—Does Surgery Tell the Whole Story?

“…This study from a tertiary referral center for pancreatic surgery examined the R-status in DP specimens with PDAC, focusing on standardization and meticulousness of the pathology work-up. 5 The introduction of a standardized grossing protocol with emphasis on extensive tissue sampling resulted in an increase in R1-rate from 60.4 to 83.1% (p = 0.005). Furthermore, it was independently associated with R1 in the multivariable model.…”