神经浸润对胃癌患者生存预后的影响
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摘要
目的:探讨神经浸润(perineural invasion,PNI)对胃癌患者生存预后的影响。方法:回顾性分析2011年1月至2012年12月天津医科大学肿瘤医院收治的1 007例胃癌患者的临床病理资料,根据术后病理标本中有无PNI将所有患者分为PNI阴性组和PNI阳性组,分析PNI与临床病理因素的关系及其对胃癌患者生存预后的影响。结果:1 007例胃癌患者中PNI阳性120例,阳性率为11.9%。分化程度、浸润深度和脉管癌栓是PNI的独立危险因素。单因素分析显示,年龄、肿瘤部位、Borrmann分型、肿瘤大小、根治度、TNM分期、术式、癌结节、脉管癌栓、PNI、术前CA19-9及CEA水平与胃癌患者预后相关。PNI阴性和PNI阳性患者5年生存率分别为66.6%和38.3%,差异具有统计学意义(P<0.001)。多因素分析显示年龄、BorrmannⅣ型、TNM分期、根治度、癌结节和PNI是胃癌患者的独立预后因素。分层分析显示,PNI仅对Ⅰ、Ⅱ和Ⅲa期胃癌预后影响具有统计学意义。结论:PNI是胃癌患者独立预后因素,可作为Ⅰ、Ⅱ和Ⅲa期患者预后评价指标。
Objective: To evaluate the impact of perineural invasion(PNI) on the overall survival(OS) of patients with gastric cancer.Methods: A total of 1,007 patients with gastric cancer who underwent curative resection between January 2011 and December 2012 at the Cancer Institute and Hospital of Tianjin Medical University were enrolled. All the patients were categorized into the following two groups according to the status of PNI: positive group, presence of PNI; and negative group, absence of PNI. Potential prognostic factors and clinical pathological variables correlated with the presence of PNI were analyzed. Results: One hundred and twenty(11.9%) patients had PNI. Multivariate analysis revealed that histology, depth of invasion, and lymphovascular invasion were indepen-dently associated with the presence of PNI. Univariate survival analysis revealed that age, tumor location, Borrmann type, tumor size,curability, TNM stage, type of gastrectomy, tumor deposit, lymphovascular invasion, PNI, preoperative CA19-9 levels, and CEA levels were significant prognostic factors. Gastric cancer patients with PNI had a significantly lower 5-year OS rate than those without PNI(5-year OS: 38.3% versus 66.6%, P<0.001). In the multivariate analysis, age, Borrmann type Ⅳ, TNM stage, curability, tumor deposit, and PNI were independent prognostic factors for this population cohort. The strata analysis revealed that PNI merely had a significant im-pact on OS in patients at stages Ⅰ,Ⅱ, and Ⅲa. Conclusions: PNI is an independent prognostic factor in patients with gastric cancer and can be used as a prognostic indicator for gastric cancer patients at stages Ⅰ,Ⅱ, and Ⅲa.
Objective: To evaluate the impact of perineural invasion(PNI) on the overall survival(OS) of patients with gastric cancer.Methods: A total of 1,007 patients with gastric cancer who underwent curative resection between January 2011 and December 2012 at the Cancer Institute and Hospital of Tianjin Medical University were enrolled. All the patients were categorized into the following two groups according to the status of PNI: positive group, presence of PNI; and negative group, absence of PNI. Potential prognostic factors and clinical pathological variables correlated with the presence of PNI were analyzed. Results: One hundred and twenty(11.9%) patients had PNI. Multivariate analysis revealed that histology, depth of invasion, and lymphovascular invasion were indepen-dently associated with the presence of PNI. Univariate survival analysis revealed that age, tumor location, Borrmann type, tumor size,curability, TNM stage, type of gastrectomy, tumor deposit, lymphovascular invasion, PNI, preoperative CA19-9 levels, and CEA levels were significant prognostic factors. Gastric cancer patients with PNI had a significantly lower 5-year OS rate than those without PNI(5-year OS: 38.3% versus 66.6%, P<0.001). In the multivariate analysis, age, Borrmann type Ⅳ, TNM stage, curability, tumor deposit, and PNI were independent prognostic factors for this population cohort. The strata analysis revealed that PNI merely had a significant im-pact on OS in patients at stages Ⅰ,Ⅱ, and Ⅲa. Conclusions: PNI is an independent prognostic factor in patients with gastric cancer and can be used as a prognostic indicator for gastric cancer patients at stages Ⅰ,Ⅱ, and Ⅲa.
引文
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[16]Yokoyama S,Matsuda K,Watanabe T,et al.Perineural invasion is as-sociated with poor survival after preoperative chemoradiation ther-apy for advanced lower rectal cancer[J].Dig Surg,2017,34(5):387-393.
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[21]Bilici A,Seker M,Ustaalioglu BB,et al.Prognostic significance of perineural invasion in patients with gastric cancer who underwent curative resection[J].Ann Surg Oncol,2010,17(8):2037-2044.
[22]Kim YB,Han SU,Lee D.Prominent neural invasion of mucosal gas-tric cancer into the muscularis propria[J].Histopathology,2017,71(4):661-662.
[23]Scartozzi M,Galizia E,Verdecchia L,et al.Lymphatic,blood vessel and perineural invasion identifies early-stage high-risk radically re-sected gastric cancer patients[J].Br J Cancer,2006,95(4):445-449.
[24]殷凯,瞿建国,陈吉祥,等.胃癌神经侵犯的相关临床病理因素:单中心509例分析[J].中国普通外科杂志,2018,27(4):396-400.
[25]陈路川,魏晟宏,叶再生,等.神经浸润对1801例胃癌术后预后的影响[J].中华消化外科杂志,2017,16(3):262-268.
[26]谢洪虎,吕成余,黄文斌.胃癌神经旁浸润的临床特征与预后分析[J].中华胃肠外科杂志,2010,13(6):413-416.
[27]纪明明,李云东,隋淑凤.胃癌神经浸润与临床病理特征的关系及对预后的影响[J].中华普通外科杂志,2015,30(5):403-404.
[28]Duraker N,Si?man S,Can G.The significance of perineural invasion as a prognostic factor in patients with gastric carcinoma[J].Surg To-day,2003,33(2):95-100.
[29]Lee D,Son SY,Kim YB,et al.Neural invasion is a significant contribu-tor to peritoneal recurrence in signet ring cell gastric carcinoma[J].Ann Surg Oncol,2018,25(5):1167-1175.
[30]Jiang N,Deng JY,Liu Y,et al.Incorporation of perineural invasion of gastric carcinoma into the 7th edition tumor-node-metastasis stag-ing system[J].Tumour Biol,2014,35(9):9429-9436.
[31]Espa?a-Ferrufino A,Lino-Silva LS,Salcedo-Hernández RA.Extramural perineural invasion in pT3 and pT4 gastric carcinomas[J].J Pathol Transl Med,2018,52(2):79-84.
[2]Aurello P,Berardi G,Tierno SM,et al.Influence of perineural inva-sion in predicting overall survival and disease-free survival in pa-tients With locally advanced gastric cancer[J].Am J Surg,2017,213(4):748-753.
[3]De Franco L,Marrelli D,Voglino C,et al.Prognostic value of peri-neural invasion in resected gastric cancer patients according to lau-ren histotype[J].Pathol Oncol Res,2018,24(2):393-400.
[4]Hwang JE,Hong JY,Kim JE,et al.Prognostic significance of the con-comitant existence of lymphovascular and perineural invasion in lo-cally advanced gastric cancer patients who underwent curative gas-trectomy and adjuvant chemotherapy[J].Jpn J Clin Oncol,2015,45(6):541-546.
[5]Yang YH,Liu JB,Gui Y,et al.Relationship between autophagy and perineural invasion,clinicopathological features,and prognosis in pancreatic cancer[J].World J Gastroenterol,2017,23(40):7232-7241.
[6]Liang D,Shi S,Xu J,et al.New insights into perineural invasion of pancreatic cancer:More than pain[J].Biochim Biophys Acta,2016,1865(2):111-122.
[7]Schorn S,Demir IE,Haller B,et al.The influence of neural invasion on survival and tumor recurrence in pancreatic ductal adenocarci-noma-A systematic review and meta-analysis[J].Surg Oncol,2017,26(1):105-115.
[8]Murakami Y,Uemura K,Sudo T,et al.Perineural invasion in extrahe-patic cholangiocarcinoma:prognostic impact and treatment strate-gies[J].J Gastrointest Surg,2013,17(8):1429-1439.
[9]Feng Y,Hu X,Liu G,et al.M3 muscarinic acetylcholine receptors regulate epithelial-mesenchymal transition,perineural invasion,and migration/metastasis in cholangiocarcinoma through the AKTpathway[J].Cancer Cell Int,2018,18:173.
[10]夏启俊,陈凛.胃癌神经侵袭的细胞与分子机制[J].中华胃肠外科杂志,2015,18(2):198-200.
[11]Lenz J,Karasek P,Jarkovsky J,et al.Clinicopathological correlations of nestin expression in surgically resectable pancreatic cancer in-cluding an analysis of perineural invasion[J].J Gastrointestin Liver Dis,2011,20(4):389-396.
[12]Zhou Y,Zhou Q,Chen R.Pancreatic stellate cells promotes the peri-neural invasion in pancreatic cancer[J].Med Hypotheses,2012,78(6):811-813.
[13]Kim HJ,Kim CY,Hur YH,et al.Prognostic factors for survival after cu-rative resection of distal cholangiocarcinoma:perineural invasion and lymphovascular invasion[J].Surg Today,2014,44(10):1879-1886.
[14]Cienfuegos JA,Martínez P,Baixauli J,et al.Perineural invasion is a major prognostic and predictive factor of response to adjuvant che-motherapy in stageⅠ-Ⅱcolon cancer[J].Ann Surg Oncol,2017,24(4):1077-1084.
[15]Kinugasa T,Mizobe T,Shiraiwa S,et al.Perineural invasion is a prog-nostic factor and treatment indicator in patients with rectal cancer undergoing curative surgery:2000-2011 data from a single-center study[J].Anticancer Res,2017,37(7):3961-3968.
[16]Yokoyama S,Matsuda K,Watanabe T,et al.Perineural invasion is as-sociated with poor survival after preoperative chemoradiation ther-apy for advanced lower rectal cancer[J].Dig Surg,2017,34(5):387-393.
[17]Carr RA,Roch AM,Zhong X,et al.Prospective evaluation of associa-tions between cancer-related pain and perineural invasion in pa-tients with resectable pancreatic adenocarcinoma[J].J Gastrointest Surg,2017,21(10):1658-1665.
[18]Sel?ukbiricik F,Tural D,Büyükünal E,et al.Perineural invasion inde-pendent prognostic factors in patients with gastric cancer undergo-ing curative resection[J].Asian Pac J Cancer Prev,2012,13(7):3149-3152.
[19]Deng J,You Q,Gao Y,et al.Prognostic value of perineural invasion in gastric cancer:a systematic review and meta-analysis[J].PLoSOne,2014,9(2):e88907.
[20]Kurtz KA,Hoffman HT,Zimmerman MB,et al.Perineural and vascu-lar invasion in oral cavity squamous carcinoma:increased inci-dence on re-review of slides and by using immunohistochemical enhancement[J].Arch Pathol Lab Med,2005,129(3):354-359.
[21]Bilici A,Seker M,Ustaalioglu BB,et al.Prognostic significance of perineural invasion in patients with gastric cancer who underwent curative resection[J].Ann Surg Oncol,2010,17(8):2037-2044.
[22]Kim YB,Han SU,Lee D.Prominent neural invasion of mucosal gas-tric cancer into the muscularis propria[J].Histopathology,2017,71(4):661-662.
[23]Scartozzi M,Galizia E,Verdecchia L,et al.Lymphatic,blood vessel and perineural invasion identifies early-stage high-risk radically re-sected gastric cancer patients[J].Br J Cancer,2006,95(4):445-449.
[24]殷凯,瞿建国,陈吉祥,等.胃癌神经侵犯的相关临床病理因素:单中心509例分析[J].中国普通外科杂志,2018,27(4):396-400.
[25]陈路川,魏晟宏,叶再生,等.神经浸润对1801例胃癌术后预后的影响[J].中华消化外科杂志,2017,16(3):262-268.
[26]谢洪虎,吕成余,黄文斌.胃癌神经旁浸润的临床特征与预后分析[J].中华胃肠外科杂志,2010,13(6):413-416.
[27]纪明明,李云东,隋淑凤.胃癌神经浸润与临床病理特征的关系及对预后的影响[J].中华普通外科杂志,2015,30(5):403-404.
[28]Duraker N,Si?man S,Can G.The significance of perineural invasion as a prognostic factor in patients with gastric carcinoma[J].Surg To-day,2003,33(2):95-100.
[29]Lee D,Son SY,Kim YB,et al.Neural invasion is a significant contribu-tor to peritoneal recurrence in signet ring cell gastric carcinoma[J].Ann Surg Oncol,2018,25(5):1167-1175.
[30]Jiang N,Deng JY,Liu Y,et al.Incorporation of perineural invasion of gastric carcinoma into the 7th edition tumor-node-metastasis stag-ing system[J].Tumour Biol,2014,35(9):9429-9436.
[31]Espa?a-Ferrufino A,Lino-Silva LS,Salcedo-Hernández RA.Extramural perineural invasion in pT3 and pT4 gastric carcinomas[J].J Pathol Transl Med,2018,52(2):79-84.