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Increased Number of Perineural Invasion Is Independently Associated With Poor Survival of Patients With Resectable Pancreatic Cancer
Naru Kondo*, Yoshiaki Murakami, Kenichiro Uemura, Takeshi Sudo, Yasushi Hashimoto, Hayato Sasaki, Taijiro Sueda
Surgery, Hiroshima Univ, Hiroshima, Japan
Background: Although perineural invasion (PNI) in pancreatic cancer has been reported to be a risk factor of poor outcome, its diagnostic criteria and the optimal cutoff values for predicting prognosis has remained controversial.
Purpose: The purpose of this study was to investigate the impact of the number of PNI in resected specimen on survival of patients underwent surgical resection for pancreatic cancer.
Methods: Two hundred and two patients with pancreatic cancer who underwent surgical resection between 1999 and 2013 were eligible for this study. Histological assessment of PNI was performed by reviewing all of the Hematoxylin and Eosin stained slides with pancreatic cancer cells and the number of PNI was determined by counting every nerve fiber with PNI in these slides. The relationships between clinicopathological factors including the number of PNI and overall survival (OS) were analyzed with univariate and multivariate analyses.
Results: PNI was observed in 190 of 202 (94%) patients and median number of PNI was 25 (range 0 - 441). The number of PNI was significantly associated with residual tumor factor (P = 0.0003), UICC T factor (P < 0.0001), lymph node metastasis (P < 0.0001), UICC stage (P < 0.0001). Univariate analysis revealed that lack of postoperative adjuvant chemotherapy (P = 0.0001), R1 resection (P < 0.0001), moderately or poorly differentiated adenocarcinoma (P = 0.004), UICC pT3 (P = 0.03), lymph node metastasis (P = 0.001) and elevated postoperative serum CA19-9 level (>37 U/ml) (P < 0.0001) were significantly associated with shorter OS. In addition, significant differences in OS were found between two groups divided on the basis of the median number of PNI (≥25 vs. 25>) (P < 0.0001) and among three groups divided on the basis of tertile (≥40 vs. 40-14 vs.14≥) (P < 0.0001). In multivariate analysis, lack of postoperative adjuvant chemotherapy (hazard ratio [HR], 2.33: 95% confidence interval [CI], 1.39 - 3.79; P = 0.001), moderately or poorly differentiated adenocarcinoma (HR, 1.71; 95% CI, 1.12 - 2.70; P = 0.01), R1 resection (HR, 1.91; 95% CI, 1.23 - 2.95; P = 0.004), elevated postoperative serum CA19-9 level (>37 U/ml) (HR, 2.94; 95% CI, 1.93 - 4.47; P < 0.0001) and increased number of PNI (≥25) (HR, 2.53; 95% CI, 1.58 - 4.18; P < 0.0001) were identified as independent risk factors of shorter OS.
Conclusion: Increased number of PNI was independent risk factor of poor survival in patients with resectable pancreatic cancer, and it may contribute to establishment of new therapeutic strategy, as postoperative treatment can be optimized based on its value.
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