Clinical impacts of resection margin status and clinicopathologic parameters on pancreatic ductal adenocarcinoma

Abstract

Background: The clinical relevance of pancreatic intraepithelial neoplasia (PanIN) at the resection margin of pancreatic ductal adenocarcinoma remains unknown. We aimed to investigate its clinical impact at the pancreatic transection margin (PTM) and, based on the result, determine the prognostic values of the resection margin status and other clinicopathologic parameters.

Patients and methods: We retrospectively analyzed 122 consecutive patients who underwent pancreatoduodenectomy or distal pancreatectomy between 2006 and 2018. Pathologic slides were reviewed and survival data were retrieved from institutional databases. Associations between two variables were investigated by Fisher's exact test. Survival curves were generated by the Kaplan-Meier method. Prognostic factors were assessed using Cox regression analysis.

Results: Tumors were resected without leaving macroscopic remnants. The median follow-up period after surgery was 524.5 days. Cancer-related death (n = 72) was marginally and significantly associated with local recurrence (n = 22) and distant metastasis (n = 79), respectively. Local recurrence and distant metastasis occurred independently. After excluding cases with invasive cancer at any other margin, PanIN-2 or PanIN-3 (n = 21) at the PTM did not adversely affect prognoses compared with normal mucosa or PanIN-1 (n = 57) with statistical significance. R0 resection (n = 78), which is invasive cancer-free at all resection margins, showed somewhat better local recurrence-free and overall survivals as compared with R1 resection (n = 44), which involves invasive cancer at any resection margin, but the differences did not reach statistical significance. In contrast, differentiation grade and nodal metastasis were significant predictors of distant metastasis, and tumor location and differentiation grade were significant predictors of cancer-related death. Although there was no significant difference in differentiation grade between the head cancer and the body or tail cancer, nodal metastasis was significantly more frequent in the former than in the latter.

Conclusions: PanINs at the PTM did not adversely affect prognosis and R0 resection was not found to be a significant prognostic factor. Differentiation grade might be an indicator of occult metastasis and affect patients' overall survival through distant metastasis. In addition to successful surgical procedures, tumor biology may be even more important as a predictor of postoperative prognosis.

Keywords: Differentiation grade; PanIN; Pancreatic ductal adenocarcinoma; Prognosis; Resection margin; Tumor biology.

Fig. 1

Histopathology of PanIN. a Normal pancreatic duct (H&E). b Hyperplastic pancreatic duct epithelium (H&E). c PanIN-1A (H&E). d PanIN-1B (H&E). e PanIN-2 (H&E). f PanIN-3 (H&E). PanIN, pancreatic intraepithelial neoplasia. Scale bar, 200 μm

Fig. 2

Survival analyses of patients with PDAC. a Local recurrence-free survivals of patients with normal mucosa or PanIN-1 and PanIN-2 or PanIN-3 at the PTM. The resection margins other than PTM are invasive cancer-free. b Overall survivals of patients with normal mucosa or PanIN-1 and PanIN-2 or PanIN-3 at the PTM. c Comparison of local recurrence-free survivals according to the resection margin status. d Comparison of overall survivals according to the resection margin status. e Comparison of overall survivals according to the differentiation grade of PDAC (G1/G2 versus G3/G4). f Comparison of overall survivals according to the differentiation grade of PDAC (G1 versus G2/G3/G4). PDAC, pancreatic ductal adenocarcinoma; PanIN, pancreatic intraepithelial neoplasia; PTM, pancreatic transection margin; G1, well-differentiated carcinoma; G2, moderately differentiated carcinoma; G3, poorly differentiated carcinoma; G4, undifferentiated carcinoma