Abstract: Objective:To investigate the relationship between perineural invasion and clinicopathological factors of gastric cancer or prognosis of patients.
Methods:The retrospective casecontrol study was conducted. The clinicopathological data of 1 801 patients with gastric cancer who were admitted to the Affiliated Tumor Hospital of Fujian Medical University between March 1999 and November 2015 were collected. All the patients received surgery in order to the radical resection of gastric cancer, and total gastrectomy or twothirds and above of gastrectomy and D₂ lymph node dissection were performed. Patients with preoperative stage III of clinical staging underwent neoadjuvant chemotherapy. Patients with T3-T4 of histopathologic stage, T1-T2 of positive lymph nodes and T2N0 of high risk factors (low differentiated tumor, lymphovascular invasion, perineural invasion and age <50 years) underwent postoperative chemotherapy. Observation indicators: (1) treatment situations; (2) pathological characteristics; (3) followup results; (4) prognostic factors. Followup using outpatient examination and telephone interview was performed once within 1 month postoperatively, once every 3 months within 2 years postoperatively and once every 6 months from 3 to 5 years postoperatively up to February 2016. Followup included inquiry, physical examination, routine blood test, biochemical test, carcinoembryonic antigen (CEA), CA199, color Doppler ultrasound or computed tomography (CT) and endoscopy. Measurement data with normal distribution were represented as ±s and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were described as M (range). Ordinal data was analyzed by the nonparametric test. The univariate analysis and multivariate analysis were done using the COX regression model. The hazard ratio (HR) and 95% confidence interval (CI) were calculated. The survival curve and survival analysis were respectively drawn and done by the KaplanMeier method and Logrank test.
Result: (1) Treatment situations: all the 1 801 patients underwent traditional open surgery, including 1 570 undergoing radical resection and 231 undergoing palliative surgery. Of 1 801 patients, 1 029 received total gastrectomy, 540 received distal gastrectomy, 201 received extended gastrectomy and 31 received resection of residual stomach. Operation time, volume of intraoperative blood loss, number of lymph node dissected and duration of hospital stay were (173±40)minutes, (224±91)mL, 30±13 and (15±9)days, respectively. Of 1 801 patients, 79 underwent preoperative neoadjuvant chemotherapy and 906 underwent postoperative adjuvant chemotherapy. (2) Pathological characteristics: results of pathological examinations of 1 801 patients showed that 509 had positive perineural invasion and 1 292 had negative perineural invasion. Tumors located in the upper region, middle region and lower region of stomach, whole stomach and stump stomach were respectively detected in 173, 189, 123, 12, 12 patients with positive perineural invasion and 395, 417, 428, 29, 23 patients with negative perineural invasion. Type Ⅰ, Ⅱ, Ⅲ and Ⅳ of Borrmann type were respectively detected in 13, 213, 244, 39 patients with positive perineural invasion and 92, 511, 629, 60 patients with negative perineural invasion. The good and poor tumor differentiations and tumor diameter <5 cm and ≥5 cm were respectively detected in 172, 337, 244, 265 patients with positive perineural invasion and 536, 756, 833, 459 patients with negative perineural invasion. Stage Ⅰ, Ⅱ, Ⅲ, Ⅳ of histopathologic stage, T1, T2, T3, T4 of invasive depth, N0, N1, N2, N3 of lymph node metastasis and positive and negative lymphovascular invasion were respectively detected in 27, 54, 346, 82, 17, 24, 26, 442, 77, 84, 109, 239, 383, 126 patients with positive perineural invasion and 263, 283, 623, 123, 188, 169, 289, 646, 409, 219, 312, 352, 437, 855 patients with negative perineural invasion, with statistically significant differences in above indexes between positive and negative perineural invasion patients (x²=14.142, Z=-2.098, 〖HT2.〗〖HT5”〗x²=9.061, 41.536, Z=-10.389, -13.824, -8.638, x²=252.624, P<0.05). (3) Followup results: 1 629 patients were followed up for 1.0-99.0 months, with a median time of 37.3 months. The 5year overall survival rate was 58.5%. (4) Prognostic factors: results of univariate analysis showed that tumor location, Borrmann type, degree of tumor differentiation, tumor diameter, histopathologic stage, invasive depth, lymph node metastasis, lymphovascular invasion and perineural invasion were factors affecting prognosis of patients with gastric cancer (HR=1.209, 1.303, 1.496, 2.303, 3.368, 2.057, 1.812, 2.013, 1.332, 95% CI: 1.123-1.301, 1.171-1.449, 1.290-1.736, 2.001-2.649, 3.012-3.767, 1.856-2.279, 1.694-1.939, 1.749-2.317, 1.126-1.576, P<0.05). Results of multivariate analysis showed that tumors located in the upper and middle of stomach, whole stomach and stump stomach, tumor diameter ≥5 cm, stage Ⅱ-Ⅳ of histopathologic stage, T2-T4 of invasive depth, N1-N3 of lymph node metastasis, positive lymphovascular invasion and positive perineural invasion were independent risk factors affecting prognosis of patients with gastric cancer (HR=1.087, 1.234, 2.663, 1.174, 1.136, 1.254, 1.272, 95% CI: 1.008-1.172, 1.063-1.432, 2.292-3.095, 1.035-1.332, 1.044-1.236, 1.064-1.501, 1.066-1.516, P<0.05). The 5year survival rate was 49.1% in 509 patients with positive perineural invasion and 60.7% in 1 292 patients with negative perineural invasion, respectively, with a statistically significant difference (x²=11.270, P<0.05). The 5year overall survival rate was 41.1% in 383 patients with positive perineural invasion and lymphovascular invasion, 77.1% in 126 patients with positive perineural invasion and negative lymphovascular invasion, 49.1% in 437 patients with negative perineural invasion and positive lymphovascular invasion and 92.1% in 855 patients with negative perineural invasion and lymphovascular invasion, respectively, with a statistically significant difference (x²=244.368, P<0.05).
Conclusion: Perineural invasion is a high risk factor affecting prognosis of patients with gastric cancer, and it may be useful in evaluating prognosis of patients with gastric cancer.