不同细胞病理学分级标准对超声内镜引导下细针穿刺诊断胰腺癌的影响

孟海轮; 李素文; 宋育林; 鲍峻峻; 刘衡; 梅俏

doi:10.3969/j.issn.1001-5256.2021.02.028

不同细胞病理学分级标准对超声内镜引导下细针穿刺诊断胰腺癌的影响

DOI: 10.3969/j.issn.1001-5256.2021.02.028

安徽医科大学第一附属医院消化内科，合肥 230022

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突，特此声明。

作者贡献声明：孟海轮、李素文、刘衡负责课题设计，资料分析，撰写论文；鲍峻峻、宋育林参与收集数据，修改论文；梅俏负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

作者简介:
孟海轮(1983—)，男，副主任医师，主要从事消化内镜临床研究

通信作者:
梅俏，meiqiao@hotmail.com

中图分类号: R735.9
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出版历程
- 收稿日期: 2020-08-16
- 录用日期: 2020-10-16
- 出版日期: 2021-02-20

Effect of different cytopathological grading standards on the diagnosis of pancreatic cancer by endoscopic ultrasound-guided fine needle aspiration

Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China

摘要

摘要: 目的探讨不同细胞病理学分级标准对超声内镜引导下细针穿刺(EUS-FNA)诊断胰腺癌效能的影响。方法收集2011年5月—2019年3月于安徽医科大学第一附属医院行EUS-FNA检查的256例胰腺占位患者的临床资料和胰腺细胞病理学诊断结果，以手术病理结果和随访情况作为最终诊断，评估影响EUS-FNA诊断效能的相关因素。计量资料两组间比较采用独立样本t检验或Mann-Whitney U检验；计数资料两组间比较采用χ²检验。应用受试者工作特征曲线(ROC曲线)评价不同细胞病理学分级标准对胰腺癌的诊断价值。结果剔除失访患者67例，共189例患者纳入研究，按巴氏细胞病理学标准，EUS-FNA诊断细胞病理学结果为异型细胞47例，疑癌细胞25例，癌细胞20例，未见肿瘤细胞97例。133例经术后病理和随访结果证实为胰腺癌，其中细胞病理学检查结果分别为：未见肿瘤细胞52例，异型细胞36例，疑癌细胞25例，癌细胞20例。EUS-FNA诊断胰腺癌的真阳性率为60.90%(81例)，假阴性率为39.10%(52例)；非胰腺癌56例，假阳性率为19.64%(11例)，真阴性率为80.36%(45例)。EUS-FNA诊断胰腺癌的ROC曲线下面积为0.643(95% CI：0.561~0.724)。联合不同细胞病理学分级标准，分别以“发现异型细胞或可疑癌细胞或癌细胞均为阳性”“发现可疑癌细胞或癌细胞均为阳性”和“发现癌细胞为阳性”为诊断标准进行分析，结果显示，以“发现异型细胞或可疑癌细胞或癌细胞均为阳性”为诊断标准，EUS-FNA诊断胰腺癌的效能提高，敏感度为50.38%，特异度为75.00%。189例患者EUS-FNA术后并发症发生率为6.88%(13例)，主要为高淀粉酶血症和腹痛。结论联合不同细胞病理学分级标准有助于提高EUS-FNA对胰腺癌的诊断效能。
- 胰腺肿瘤 /
- 内镜超声引导细针穿刺 /
- 诊断
Abstract: Objective To investigate the effect of different cytopathological grading standards on the efficiency of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of pancreatic cancer. Methods Related clinical data and pancreatic cytopathological results were collected from 256 patients with pancreatic space-occupying lesions who underwent EUS-FNA in The First Affiliated Hospital of Anhui Medical University from May 2011 to March 2019, and the influencing factors for the diagnostic efficiency of EUS-FNA were analyzed based on surgical pathology and follow-up results. The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of different cytopathological grading standards in the diagnosis of pancreatic cancer. Results A total of 67 patients who were lost to follow-up were excluded, and a total of 189 patients were included in the study. According to the Papanicolaou cytopathological standard, there were 47 cases of heterotypic cells, 25 cases of suspected cancer cells, 20 cases of cancer cells, and 97 cases without tumor cells based on EUS-FNA. A total of 133 patients were confirmed to have pancreatic cancer by postoperative pathology and follow-up results, among whom 52 had no tumor cells, 36 had heterotypic cells, 25 had suspected cancer cells, and 20 had cancer cells based on cytopathological results. EUS-FNA had a true positive rate of 60.90% (81 patients) and a false negative rate of 39.10% (52 patients) in the diagnosis of pancreatic cancer; for the 56 patients without pancreatic cancer, EUS-FNA had a false positive rate of 19.64% (11 patients) and a true negative rate of 80.36% (45 patients). EUS-FNA had an area under the ROC curve of 0.643 (95% confidence interval: 0.561-0.724) in the diagnosis of pancreatic cancer. In combination with different cytopathological grading standards and with the diagnostic criteria of "the identification of heterotypic cells or suspected cancer cells or cancer cells was considered positive", "the identification of suspected cancer cells or cancer cells was considered positive", and "the identification of cancer cells was considered positive", the results showed that the diagnostic criteria of "the identification of heterotypic cells or suspected cancer cells or cancer cells was considered positive" improved the efficiency of EUS-FNA in the diagnosis of pancreatic cancer, with a sensitivity of 50.38% and a specificity of 75.00%. Among the 189 patients, 13 (6.88%) experienced complications after EUS-FNA, which included hyperamylasemia and abdominal pain. Conclusion The combination of different cytopathological grading standards can help improve the efficiency of EUS-FNA in the diagnosis of pancreatic cancer.
- Pancreatic Neoplasms /
- Endoscopic Ultrasound-Guided Fine Needle Aspiration /
- Diagnosis

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图 1 EUS-FNA诊断胰腺癌的ROC曲线

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表 1 胰腺癌与非胰腺癌组患者的临床特征比较

指标	非胰腺癌组(n=56)	胰腺癌组(n=133)	统计值	P值
男[例(%)]	32(57.1)	85(63.9)	χ²=0.765	0.382
年龄(岁)	54.9±14.3	63.3±11.4	t=4.257	＜0.001
非甾体抗炎药用药史[例(%)]	1(1.8)	12(9.0)	χ²=2.191	0.139
糖尿病史[例(%)]	5(8.9)	17(12.8)	χ²=0.569	0.451
胰腺炎病史[例(%)]	14(25.0)	12(9.0)	χ²=8.479	0.004
WBC(10⁹/L)	6.02±2.08	5.72±1.95	t=0.924	0.357
RBC(10¹²/L)	4.32±0.64	4.16±0.63	t=1.588	0.114
Hb(g/L)	124.16±20.47	122.11±17.94	t=0.686	0.494
PLT(10⁹/L)	214.61±88.11	186.88±80.94	t=2.086	0.038
血清Ca²⁺(mmol/L)	2.28±0.12	2.27±0.18	t=0.158	0.875
肌酐(μmol/L)	60.62±14.50	18.05±1.64	t=1.431	0.154
尿素氮(mmol/L)	5.30(4.31~6.05)	5.23(3.83~6.49)	U=1497.50	0.858
Alb(g/L)	40.30±4.76	40.69±0.57	t=0.414	0.679
TBil(μmol/L)	13.36(10.81~14.62)	19.85(12.15~29.78)	U=1668.00	0.081
DBil(μmol/L)	2.72(2.04~3.60)	4.24(3.76~16.86)	U=1588.00	＜0.001
ALT(U/L)	16.00(14.00~18.00)	26.50(14.50~138.50)	U=1819.50	0.072
AST(U/L)	19.00(15.00~24.00)	27.50(17.00~74.00)	U=1792.50	0.117
GGT(U/L)	22.00(19.00~29.00)	48.00(22.00~315.50)	U=1591.00	0.002
ALP(U/L)	103.00(95.00~127.00)	115.00(66.00~347.50)	U=3070.00	0.266
CRP(mg/L)	4.74(0.79~62.18)	4.02(1.52~18.08)	U=638.00	0.827
Glu(mmol/L)	6.40±3.07	6.57±1.97	t=0.356	0.723
脂肪酶(U/L)	43.00(25.00~80.00)	51.00(24.00~329.00)	U=501.50	0.106
淀粉酶(U/L)	72.00(61.00~80.00)	67.50(39.00~128.00)	U=2166.00	0.223
CA19-9(U/L)	59.94(10.19~192.30)	141.00(30.03~298.80)	U=1590.50	＜0.001
CEA(mg/ml)	2.00(1.00~3.00)	3.00(2.00~5.00)	U=1878.00	＜0.001

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表 2 胰腺癌与非胰腺癌组患者EUS特征比较

项目	非胰腺癌组(n=56)	胰腺癌组(n=133)	χ²值	P值
病变部位(例)			0.015	0.904
胰头部	34	82
胰体尾部	22	51
胰管扩张[例(%)]	18(32.1)	70(52.6)	6.649	0.010
边界清晰[例(%)]	36(64.3)	34(25.6)	25.338	＜0.001
性质(例)			6.888	0.009
囊性/囊实性	20	24
实性	36	109
低回声[例(%)]	43(76.8)	121(91.0)	6.915	0.009

下载: 导出CSV

表 3 EUS-FNA细胞学结果诊断胰腺癌效能分析

EUS-FNA结果	AUC	敏感度(%)	特异度(%)	Youden指数	Kappa(%)	阳性预测值(%)	阴性预测值(%)	假阴性率(%)	假阳性率(%)
发现异型细胞或可疑癌细胞或癌细胞均为阳性	0.643	50.38	75.00	0.25	20.00	82.71	38.89	49.62	25.00
发现可疑癌细胞或癌细胞均为阳性	0.606	30.08	91.07	0.21	14.53	88.89	35.42	69.92	8.92
发现癌细胞为阳性	0.550	13.53	96.43	0.10	6.29	90.00	31.95	86.47	3.57

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参考文献(21)

[1]	KANDEL P, WALLACE MB. Advanced EUS guided tissue acquisition methods for pancreatic cancer[J]. Cancers (Basel), 2018, 10(2): 54. DOI: 10.3390/cancers10020054
[2]	JIN KZ, HUANG QY, LIU C, et al. New advances in diagnosis and treatment of pancreatic cancer[J]. Chin J Dig Surg, 2019, 18(7): 657-661. (in Chinese) DOI: 10.3760/cma.j.issn.1673-9752.2019.07.009 金凯舟, 黄秋依, 刘辰, 等. 胰腺癌诊断与治疗的新进展[J]. 中华消化外科杂志, 2019, 18(7): 657-661. DOI: 10.3760/cma.j.issn.1673-9752.2019.07.009
[3]	CAǦLAR E, HATEMI I, ATASOY D, et al. Concordance of endoscopic ultrasonography-guided fine needle aspiration diagnosis with the final diagnosis in subepithelial lesions[J]. Clin Endosc, 2013, 46(4): 379-383. DOI: 10.5946/ce.2013.46.4.379
[4]	YANG F, YANG F, SUN SY. Endoscopic ultrasound diagnosis of space-occupying lesions in the pancreas[J]. J Clin Hepatol, 2020, 36(8): 1704-1709. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.08.005 杨帆, 杨飞, 孙思予. 胰腺占位性病变的超声内镜诊断[J]. 临床肝胆病杂志, 2020, 36(8): 1704-1709. DOI: 10.3969/j.issn.1001-5256.2020.08.005
[5]	WANG W, SHPANER A, KRISHNA SG, et al. Use of EUS-FNA in diagnosing pancreatic neoplasm without a definitive mass on CT[J]. Gastrointest Endosc, 2013, 78(1): 73-80. DOI: 10.1016/j.gie.2013.01.040
[6]	ELTOUM IA, ALSTON EA, ROBERSON J. Trends in pancreatic pathology practice before and after implementation of endoscopic ultrasound-guided fine-needle aspiration: An example of disruptive innovation effect?[J]. Arch Pathol Lab Med, 2012, 136(4): 447-453. DOI: 10.5858/arpa.2011-0218-OA
[7]	LAYFIELD LJ, DODD L, FACTOR R, et al. Malignancy risk associated with diagnostic categories defined by the Papanicolaou Society of Cytopathology pancreaticobiliary guidelines[J]. Cancer Cytopathol, 2014, 122(6): 420-427. DOI: 10.1002/cncy.21386
[8]	HEWITT MJ, McPHAIL MJ, POSSAMAI L, et al. EUS-guided FNA for diagnosis of solid pancreatic neoplasms: A meta-analysis[J]. Gastrointest Endosc, 2012, 75(2): 319-331. DOI: 10.1016/j.gie.2011.08.049
[9]	KIM SH, WOO YS, LEE KH, et al. Preoperative EUS-guided FNA: Effects on peritoneal recurrence and survival in patients with pancreatic cancer[J]. Gastrointest Endosc, 2018, 88(6): 926-934. DOI: 10.1016/j.gie.2018.06.024
[10]	YAN H, JIA A, ZHANG J, et al. The diagnostic value of endoscopic ultrasonography-guided fine needle aspiration for pancreatic space-occupying diseases[J]. J Xi'an Jiaotong Univ(Med Sci), 2020, 41(3): 425-428. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-XAYX202003021.htm 严欢, 贾皑, 张娟, 等. 超声内镜引导细针穿刺活检对胰腺占位性疾病的诊断价值[J]. 西安交通大学学报(医学版), 2020, 41(3): 425-428. https://www.cnki.com.cn/Article/CJFDTOTAL-XAYX202003021.htm
[11]	KITANO M, YOSHIDA T, ITONAGA M, et al. Impact of endoscopic ultrasonography on diagnosis of pancreatic cancer[J]. J Gastroenterol, 2019, 54(1): 19-32. DOI: 10.1007/s00535-018-1519-2
[12]	CAZACU IM, LUZURIAGA CHAVEZ AA, SAFTOIU A, et al. A quarter century of EUS-FNA: Progress, milestones, and future directions[J]. Endosc Ultrasound, 2018, 7(3): 141-160. DOI: 10.4103/eus.eus_19_18
[13]	LEBLANC JK, EMERSON RE, DEWITT J, et al. A prospective study comparing rapid assessment of smears and ThinPrep for endoscopic ultrasound-guided fine-needle aspirates[J]. Endoscopy, 2010, 42(5): 389-394. DOI: 10.1055/s-0029-1243841
[14]	SHAH T, ZFASS AM. Accuracy of EUS-FNA in solid pancreatic lesions: Sometimes size does matter[J]. Dig Dis Sci, 2019, 64(7): 1734-1735. DOI: 10.1007/s10620-019-5468-2
[15]	ZHANG Y, ZHU Q, GONG TT, et al. Diagnostic value of EUS-FNA for pancreatic masses and its influential factors[J]. Chin J Dig Endosc, 2011, 28(9): 492-496. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-YBQJ202006002.htm 张燚, 诸琦, 龚婷婷, 等. 内镜超声引导下细针穿刺抽吸术对胰腺占位病变诊断价值及其影响因素的研究[J]. 中华消化内镜杂志, 2011, 28(9): 492-496. https://www.cnki.com.cn/Article/CJFDTOTAL-YBQJ202006002.htm
[16]	FAN Z, ZHANG L, ZHANG XF, et al. The diagnostic value of endoscopic ultrasonography guided fine needle aspiration for occupying pancreatic lesions[J]. Chin J Dig Endosc, 2016, 33(12): 847-850. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZHXH200705001.htm 范震, 张乐, 张筱凤, 等. 内镜超声引导下细针穿刺活检对胰腺占位性病变的诊断价值[J]. 中华消化内镜杂志, 2016, 33(12): 847-850. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHXH200705001.htm
[17]	BERGERON JP, PERRY KD, HOUSER PM, et al. Endoscopic ultrasound-guided pancreatic fine-needle aspiration: Potential pitfalls in one institution's experience of 1212 procedures[J]. Cancer Cytopathol, 2015, 123(2): 98-107.
[18]	SIDDIQUI AA, KOWALSKI TE, SHAHID H, et al. False-positive EUS-guided FNA cytology for solid pancreatic lesions[J]. Gastrointest Endosc, 2011, 74(3): 535-540.
[19]	LI YQ, WANG W, SUN LQ, et al. Factors influencing the diagnostic positivity of endoscopic ultrasound guided fine needle aspiration for small pancreatic cancer and the occurrence of postoperative advent events[J]. Chin J Pancreatol, 2018, 18(4): 224-227. (in Chinese) http://med.wanfangdata.com.cn/Paper/Detail?id=PeriodicalPaper_yxbx201804003 李玉琼, 王伟, 孙力祺, 等. 影响EUS-FNA的小胰腺癌诊断阳性率及术后并发症发生的相关因素[J]. 中华胰腺病杂志, 2018, 18(4): 224-227. http://med.wanfangdata.com.cn/Paper/Detail?id=PeriodicalPaper_yxbx201804003
[20]	GLEESON FC, KIPP BR, CAUDILL JL, et al. False positive endoscopic ultrasound fine needle aspiration cytology: Incidence and risk factors[J]. Gut, 2010, 59(5): 586-593.
[21]	YOSHINAGA S, ITOI T, YAMAO K, et al. Safety and efficacy of endoscopic ultrasound-guided fine needle aspiration for pancreatic masses: A prospective multicenter study[J]. Dig Endosc, 2020, 32(1): 114-126.