外科理论与实践 ›› 2025, Vol. 30 ›› Issue (06): 509-516.doi: 10.16139/j.1007-9610.2025.06.09
王敬源a, 范嘉裕a, 张平平a, 马洪运b, 陈颖c, 李刚b, 金震东a, 金钢b(
), 王凯旋a(
)
收稿日期:2025-06-30
出版日期:2025-11-25
发布日期:2026-01-26
通讯作者:
金钢,E-mail:Jingang@smmu.edu.cn;作者简介:第一联系人:*: 共同第一作者
WANG Jingyuana, FAN Jiayua, ZHANG Pingpinga, MA Hongyunb, CHEN Yingc, LI Gangb, JIN Zhendonga, JIN Gangb(
), WANG Kaixuana(
)
Received:2025-06-30
Online:2025-11-25
Published:2026-01-26
摘要:
目的:探究囊液性状对导管内乳头状黏液性肿瘤(IPMN)良、恶性的预测能力。方法:前瞻性地收集从2023年9月至2024年12月在上海长海医院肝胆胰脾外科接受胰腺切除术且最终病理检查确认为IPMN病人的新鲜囊液。对囊液进行性状特征评估,包括黏稠度、清澈度、颜色,并探讨其对良、恶性的预测性能。结果:本研究共纳入40例IPMN病人。拉丝实验(+)对高级别异型增生/侵袭性癌(HGD/IC)的诊断灵敏度90.9%,特异度92.9%,准确率76.0%。肠型IPMN囊液常表现为胶冻样,胶冻样在HGD/IC组与LGD低级别异型增生(LGD)组分布差异无统计学意义。囊液CEA、葡萄糖、淀粉酶在HGD/IC组与LGD组差异无统计学意义。结论:胰腺囊液的性状,尤其是黏稠度,可有效预测IPMN良、恶性。
中图分类号:
王敬源, 范嘉裕, 张平平, 马洪运, 陈颖, 李刚, 金震东, 金钢, 王凯旋. 囊液性状可预测胰腺导管内乳头状黏液性肿瘤的良、恶性[J]. 外科理论与实践, 2025, 30(06): 509-516.
WANG Jingyuan, FAN Jiayu, ZHANG Pingping, MA Hongyun, CHEN Ying, LI Gang, JIN Zhendong, JIN Gang, WANG Kaixuan. Characteristics of cyst fluid can predict the benign or malignant nature of intraductal papillary mucinous neoplasms[J]. Journal of Surgery Concepts & Practice, 2025, 30(06): 509-516.
表1
病人基线特征[$\overline{x}\pm s$/n(%)/M(Q1, Q3)]
| Characteristics | HGD/IC (n=19) | LGD (n=21) | Test statistic | P value |
|---|---|---|---|---|
| Gender | χ2=0.852 | 0.356 | ||
| Male | 9 (47.4) | 13 (61.9) | ||
| Female | 10 (52.6) | 8 (38.1) | ||
| Age at surgery | 60.68±1.84 | 61.90±1.75 | t=0.481 | 0.633 |
| Cyst location | / | 0.050 | ||
| Head&Neck | 13 (68.4) | 13 (61.9) | ||
| Body&Tail | 2 (10.5) | 8 (38.1) | ||
| Whole | 4 (21.1) | 0 | ||
| Type of IPMN | / | 0.125 | ||
| BD-IPMN | 8 (42.1) | 6 (28.6) | ||
| MD-IPMN | 2 (10.5) | 0 | ||
| MT-IPMN | 9 (47.4) | 15 (71.4) | ||
| Serum CEA | 2.20 (1.92,2.96) | 2.77 (1.53,3.69) | U=213 | 0.728 |
| Serum CA19-9 | 20.79 (13.49,23.96) | 21.39 (18.05,24.09) | U=221 | 0.573 |
| Acute pancreatitis secondary to the cyst | χ2=0.151 | 0.698 | ||
| Present | 7 (36.8) | 9 (42.9) | ||
| Absent | 12 (63.2) | 12 (57.1) | ||
| Obstructive jaundice caused by cystic lesion of the head of the pancreas | χ2=1.67 | 0.196 | ||
| Present | 3 (15.8) | 0 | ||
| Absent | 16 (84.2) | 21 (100.0) | ||
| An enhancing mural nodule≥5 mm or solid component | χ2=15.506 | <0.001 | ||
| Present | 12 (63.2) | 1 (4.8) | ||
| Absent | 7 (36.8) | 20 (95.2) | ||
| Diameter of main pancreatic duct | U=224 | 0.520 | ||
| <5 mm | 6 (31.6) | 3 (14.3) | ||
| ≥5 mm~<10 mm | 9 (47.4) | 14 (66.7) | ||
| ≥10 mm | 4 (21.0) | 4 (19.0) | ||
| Main pancreatic duct stenosis with upstream pancreatic atrophy | χ2=1.160 | 0.281 | ||
| Present | 4 (21.1) | 1 (4.8) | ||
| Absent | 15 (78.9) | 20 (95.2) | ||
| Diameter of cyst | χ2=0.351 | 0.554 | ||
| <30 mm | 10 (52.6) | 13 (61.9) | ||
| ≥30 mm | 9 (47.4) | 8 (38.1) | ||
| New onset or acute exacerbation of diabetes within past one year | / | 0.219 | ||
| Present | 2 (10.5) | 0 | ||
| Absent | 17 (89.5) | 21 (100.0) | ||
| Lymphadenopathy | χ2=0.008 | 0.928 | ||
| Present | 2 (10.5) | 1 (4.8) | ||
| Absent | 17 (89.5) | 21(95.2) | ||
| Thickened/enhancing cyst wall | χ2=0.001 | 1.000 | ||
| Present | 5 (26.3) | 5 (23.8) | ||
| Absent | 14 (73.7) | 16 (76.2) |
表2
囊液性状与异型增生等级的关系[n(%)]
| Characteristics | Classification | Grade of dysplasia | Test statistic | P value | |
|---|---|---|---|---|---|
| HGD/IC(n=19) | LGD(n=21) | ||||
| Viscosity | String sign (-) | 1 (5.3) | 13 (61.9) | U=117.5 | 0.025 |
| String sign (+) | 10 (52.6) | 1 (4.8) | |||
| Gelatinous | 8 (42.1) | 7 (33.3) | |||
| Clarity | Clear | 9 (47.4) | 18 (85.7) | χ2=6.686 | 0.01 |
| Turbid | 10 (52.6) | 3 (14.3) | |||
| Color | Colorless | 4 (21.05) | 10 (47.6) | U=138.0 | 0.099 |
| Yellow | 4 (21.05) | 3 (14.3) | |||
| Red | 9 (47.4) | 8 (38.1) | |||
| Brown | 2 (10.5) | 0 | |||
表3
囊液性状与异型增生等级的关系(排除胶冻样囊液样本)[n(%)]
| Characteristics | Classification | Grade of dysplasia | P value | |
|---|---|---|---|---|
| HGD/IC(n=11) | LGD(n=14) | |||
| String sign | (-) | 1(9.1) | 13(92.9) | <0.001 |
| (+) | 10(90.9) | 1(7.1) | ||
| Clarity | Clear | 6(54.5) | 14(100.0) | 0.009 |
| Turbid | 5(45.5) | 0 | ||
| String sign combined with clarity | (-) | 1(9.1) | 13(92.9) | <0.001 |
| (+) | 10(90.9) | 1(7.1) | ||
表4
囊液其他特征[M(Q1, Q3)]
| Characteristics | Grade of dysplasia | Mann-Whitney U value | P value | |
|---|---|---|---|---|
| HGD/IC | LGD | |||
| Cyst fluid CEA (μg/L) | 21.12 (17.87, 23.88) | 22.94 (18.32, 23.8) | 157 | 0.397 |
| Cyst fluid glucose(mmol/L) | 1.04 (0.26, 1.61) | 0.59 (0.25, 1.05) | 101 | 0.540 |
| Cyst fluid amylase(IU/L) | 1363 (580, 4561) | 3148 (991.5, 5770) | 151 | 0.305 |
表6
囊液性状与形态学亚型的关系[n(%)]
| Characteristics | Classification | Morphological subtype | Test statistic | P value | ||
|---|---|---|---|---|---|---|
| Gastric | Intestinal | Pancreatobiliary | ||||
| Viscosity | String sign (-) | 12 (70.6) | 1 (7.1) | 1 (11.1) | Hc=16.210 | <0.001 |
| String sign (+) | 3 (17.6) | 3 (21.4) | 5 (55.6) | |||
| Gelatinous | 2 (11.8) | 10 (71.4) | 3 (33.3) | |||
| Clarity | Clear | 15 (88.2) | 7 (50.0) | 5 (55.6) | χ2=5.872 | 0.053 |
| Turbid | 2 (11.8) | 7 (50.0) | 4 (44.4) | |||
| Color | Colorless | 10 (58.8) | 1 (7.1) | 3 (33.3) | Hc=4.324 | 0.115 |
| Yellow | 1 (5.9) | 5 (35.7) | 1 (11.1) | |||
| Red | 5 (29.4) | 7 (50.0) | 5 (55.6) | |||
| Brown | 1 (5.9) | 1 (7.1) | 0 | |||
| [1] |
OHTSUKA T, CASTILLO C F del, FURUKAWA T, et al. International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas[J]. Pancreatology, 2024, 24(2):255-270.
doi: 10.1016/j.pan.2023.12.009 URL |
| [2] |
STARK A, DONAHUE TR, REBER HA, et al. Pancreatic cyst disease: a review[J]. JAMA, 2016, 315(17):1882-1893.
doi: 10.1001/jama.2016.4690 pmid: 27139061 |
| [3] |
LEVINK I, SPRIJ M L J A, KOOPMANN B, et al. Small and stable pancreatic cysts are reassuring during surveillance: results from the PACYFIC trial[J]. United European Gastroenterology J, 2025, 13(6):971-981.
doi: 10.1002/ueg2.v13.6 URL |
| [4] |
VAN HUIJGEVOORT N C M, DEL CHIARO M, WOLFGANG C L, et al. Diagnosis and management of pancreatic cystic neoplasms: current evidence and guidelines[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(11):676-689.
doi: 10.1038/s41575-019-0195-x |
| [5] |
BICK B L, ENDERS F T, LEVY M J, et al. The string sign for diagnosis of mucinous pancreatic cysts[J]. Endoscopy, 2015, 47(7):626-631.
doi: 10.1055/s-0034-1391484 pmid: 25730281 |
| [6] |
OH S H, LEE J K, LEE K T, et al. The combination of cyst fluid carcinoembryonic antigen, cytology and viscosi-ty increases the diagnostic accuracy of mucinous pancreatic cysts[J]. Gut Liver, 2017, 11(2):283-289.
doi: 10.5009/gnl15650 URL |
| [7] |
LEUNG KK, ROSS WA, EVANS D, et al. Pancreatic cystic neoplasm: the role of cyst morphology, cyst fluid analysis, and expectant management[J]. Ann Surg Oncol, 2009, 16(10):2818-2824.
doi: 10.1245/s10434-009-0502-9 pmid: 19536601 |
| [8] | 李兆申, 金震东, 李汛. 中国胰腺囊性肿瘤诊断指南(2022年)[J]. 临床肝胆病杂志, 2023, 39(2):290-298. |
| LI Z S, JIN Z D, LI X. Chinese guidelines for the diagnosis and treatment of pancrestic cystic neoplasm(2022)[J]. J Clin Hepatol, 2023, 39(2):290-298. | |
| [9] |
MAKER A V, CARRARA S, JAMIESON N B, et al. Cyst fluid biomarkers for intraductal papillary mucinous neoplasms of the pancreas: a critical review from the international expert meeting on pancreatic branch-duct-intraductal papillary mucinous neoplasms[J]. J Am Coll Surg, 2015, 220(2):243-253.
doi: 10.1016/j.jamcollsurg.2014.11.001 URL |
| [10] |
SUZUKI R, THOSANI N, ANNANGI S, et al. Diagnostic yield of EUS-FNA-based cytology distinguishing malignant and benign IPMNs: a systematic review and meta-analysis[J]. Pancreatology, 2014, 14(5):380-384.
doi: 10.1016/j.pan.2014.07.006 pmid: 25278308 |
| [11] |
MAIRE F, VOITOT H, AUBERT A, et al. Intraductal papillary mucinous neoplasms of the pancreas: performance of pancreatic fluid analysis for positive diagnosis and the prediction of malignancy[J]. Am J Gastroenterol, 2008, 103(11):2871-2877.
doi: 10.1111/j.1572-0241.2008.02114.x pmid: 18775021 |
| [12] |
KHALID A, ZAHID M, FINKELSTEIN S D, et al. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study[J]. Gastrointest Endosc, 2009, 69(6):1095-1102.
doi: 10.1016/j.gie.2008.07.033 pmid: 19152896 |
| [13] |
NGAMRUENGPHONG S, BARTEL M, RAIMONDO M. Cyst carcinoembryonic antigen in differentiating pancreatic cysts: a meta-analysis[J]. Dig Liver Dis, 2013, 45(11):920-926.
doi: 10.1016/j.dld.2013.05.002 URL |
| [14] | CORREA-GALLEGO C, WARSHAW AL, FERNANDEZ-DEL CASTILLO C. Fluid CEA in IPMNs: a useful test or the flip of a coin?[J]. Am J Gastroenterol, 2009, 104(3):796-797. |
| [15] |
SHI J, YI Z, JIN L, et al. Cyst fluid metabolites distinguish malignant from benign pancreatic cysts[J]. Neoplasia, 2021, 23(11):1078-1088.
doi: 10.1016/j.neo.2021.09.004 pmid: 34583246 |
| [16] |
PARK W G U, MASCARENHAS R, PALAEZ-LUNA M, et al. Diagnostic performance of cyst fluid carcinoembryonic antigen and amylase in histologically confirmed pancreatic cysts[J]. Pancreas, 2011, 40(1):42-45.
doi: 10.1097/MPA.0b013e3181f69f36 URL |
| [17] |
DAS K K, GENG X, BROWN J W, et al. Cross validation of the monoclonal antibody Das-1 in identification of high-risk mucinous pancreatic cystic lesions[J]. Gastroenterology, 2019, 157(3):720-730.e2.
doi: S0016-5085(19)40895-0 pmid: 31175863 |
| [18] |
HATA T, DAL MOLIN M, SUENAGA M, et al. Cyst fluid telomerase activity predicts the histologic grade of cystic neoplasms of the pancreas[J]. Clin Cancer Res, 2016, 22(20):5141-5151.
pmid: 27230749 |
| [19] | MAKER A, KATABI N, QIN L X, et al. Cyst fluid interleukin-1β (IL1β) levels predict the risk of carcinoma in intraductal papillary mucinous neoplasms of the pancreas[J]. Clinl Cancer Res, 2011, 17(6):1502-1508. |
| [20] |
HAAB B B, PORTER A, YUE T, et al. Glycosylation variants of mucins and ceacams as candidate biomarkers for the diagnosis of pancreatic cystic neoplasms[J]. Ann Surg, 2010, 251(5):937-945.
doi: 10.1097/SLA.0b013e3181d7738d pmid: 20395854 |
| [21] |
TANAKA M, HECKLER M, LIU B, et al. Cytologic analysis of pancreatic juice increases specificity of detection of malignant ipmn-a systematic review[J]. Clin Gastroenterol h, 2019, 17(11):2199-2211,e21.
doi: S1542-3565(19)30007-2 pmid: 30630102 |
| [22] |
STELOW E B, STANLEY M W, BARDALES R H, et al. Intraductal papillary mucinous neoplasm of the pancreas. The findings and limitations of cytologic samples obtained by endoscopic ultrasound-guided fine-needle aspiration[J]. Am J Clin Pathol, 2003, 120(3):398-404.
doi: 10.1309/CEPK542W38852LP8 URL |
| [23] |
GIANNONE F, CRIPPA S, ALEOTTI F, et al. Improving diagnostic accuracy and appropriate indications for surgery in pancreatic cystic neoplasms: the role of endoscopic ultrasound[J]. Gastrointest Endosc, 2022, 96(4):648-656.e2.
doi: 10.1016/j.gie.2022.05.009 URL |
| [24] |
THOSANI N, THOSANI S, QIAO W, et al. Role of EUS-FNA-based cytology in the diagnosis of mucinous pancreatic cystic lesions: a systematic review and meta-analysis[J]. Dig Dis Sci, 2010, 55(10):2756-2766.
doi: 10.1007/s10620-010-1361-8 URL |
| [25] |
WANG QX, XIAO J, ORANGE M, et al. EUS-guided FNA for diagnosis of pancreatic cystic lesions: a meta-analysis[J]. Cell Physiol Biochem, 2015, 36(3):1197-1209.
doi: 10.1159/000430290 URL |
| [26] |
KOH Y, ZHENG H L, CHOK A Y, et al. Systematic review and meta-analysis of the spectrum and outcomes of different histologic subtypes of noninvasive and invasive intraductal papillary mucinous neoplasms[J]. Surgery, 2015, 157(3):496-509.
doi: 10.1016/j.surg.2014.08.098 URL |
| [27] |
DISTLER M, KERSTING S, NIEDERGETHMANN M, et al. Pathohistological subtype predicts survival in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas[J]. Ann Surg, 2013, 258(2):324-330.
doi: 10.1097/SLA.0b013e318287ab73 pmid: 23532107 |
| [28] |
KIM J, JANG K T, MO PARK S, et al. Prognostic re-levance of pathologic subtypes and minimal invasion in intraductal papillary mucinous neoplasms of the pancreas[J]. Tumour Biol, 2011, 32(3):535-542.
doi: 10.1007/s13277-010-0148-z URL |
| [29] |
FURUKAWA T, HATORI T, FUJITA I, et al. Prognostic relevance of morphological types of intraductal papillary mucinous neoplasms of the pancreas[J]. Gut, 2011, 60(4):509-516.
doi: 10.1136/gut.2010.210567 pmid: 21193453 |
| [30] |
KANG M J, LEE K B, JANG J Y, et al. Evaluation of clinical meaning of histological subtypes of intraductal papillary mucinous neoplasm of the pancreas[J]. Pancreas, 2013, 42(6):959-966.
doi: 10.1097/MPA.0b013e31827cddbc URL |
| [31] |
TANAKA M, FERNÁNDEZ-DEL CASTILLO C, ADSAY V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas[J]. Pancreatology, 2012, 12(3):183-197.
doi: 10.1016/j.pan.2012.04.004 pmid: 22687371 |
| [32] |
ATTIYEH M A, FERNÁNDEZ-DEL CASTILLO C, AL EFISHAT M, et al. Development and validation of a multi-institutional preoperative nomogram for predicting grade of dysplasia in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas: a report from the pancreatic surgery consortium[J]. Ann Surg, 2018, 267(1):157-163.
doi: 10.1097/SLA.0000000000002015 pmid: 28079542 |
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