von Hippel‑Lindau综合征合并胰腺病变的临床影像学特征及预后分析

陈秋争, 周靖程, 刘宗昊, 郭小超, 刘伟康, 田孝东, 龚侃, 杨尹默

陈秋争, 周靖程, 刘宗昊, 等. von Hippel‑Lindau综合征合并胰腺病变的临床影像学特征及预后分析[J]. 中华消化外科杂志, 2023, 22(5): 650-656. DOI: 10.3760/cma.j.cn115610-20230417-00172
引用本文: 陈秋争, 周靖程, 刘宗昊, 等. von Hippel‑Lindau综合征合并胰腺病变的临床影像学特征及预后分析[J]. 中华消化外科杂志, 2023, 22(5): 650-656. DOI: 10.3760/cma.j.cn115610-20230417-00172
Chen Qiuzheng, Zhou Jingcheng, Liu Zonghao, et al. Clinical imaging features and prognosis of von Hippel‑Lindau syndrome associated with pancreatic lesions[J]. Chinese Journal of Digestive Surgery, 2023, 22(5): 650-656. DOI: 10.3760/cma.j.cn115610-20230417-00172
Citation: Chen Qiuzheng, Zhou Jingcheng, Liu Zonghao, et al. Clinical imaging features and prognosis of von Hippel‑Lindau syndrome associated with pancreatic lesions[J]. Chinese Journal of Digestive Surgery, 2023, 22(5): 650-656. DOI: 10.3760/cma.j.cn115610-20230417-00172

von Hippel‑Lindau综合征合并胰腺病变的临床影像学特征及预后分析

基金项目: 

国家自然科学基金 81871954

详细信息
    通讯作者:

    杨尹默,Email:yangyinmo@263.net

Clinical imaging features and prognosis of von Hippel‑Lindau syndrome associated with pancreatic lesions

Funds: 

National Natural Science Foundation of China 81871954

More Information
  • 摘要:
    目的 

    探讨von Hippel‑Lindau(VHL)综合征合并胰腺病变的临床影像学特征和预后。

    方法 

    采用回顾性病例对照研究方法。收集2010年9月至2022年8月北京大学第一医院收治161例VHL综合征患者的临床病理资料;男83例,女78例;发病年龄为27.0(8.0~66.0)岁。观察指标:(1)VHL综合征合并胰腺病变患者影像学检查结果。(2)VHL综合征合并胰腺病变患者的临床特征。(3)VHL综合征合并胰腺囊性病变患者的临床病理因素比较。(4)VHL综合征合并胰腺神经内分泌肿瘤(pNENs)患者的临床病理因素比较。(5)VHL综合征合并胰腺病变患者的治疗及预后。正态分布的计量资料以x±s表示,组间比较采用独立样本t检验;偏态分布的计量资料以M(范围)表示,组间比较采用非参数检验。计数资料以绝对数表示,组间比较采用χ²检验。

    结果 

    (1)VHL综合征合并胰腺病变患者影像学检查结果:161例VHL综合征患者中,合并胰腺病变151例,未发现胰腺病变10例。151例VHL综合征合并胰腺病变患者中,合并胰腺囊性病变136例,合并pNENs 34例,同时合并胰腺囊性病变和pNENs 22例,无法准确判断胰腺病变类型3例。(2)VHL综合征合并胰腺病变患者的临床特征:151例VHL综合征合并胰腺病变患者发病年龄为33.0(14.0~68.0)岁;其中外显子1、2、3、其他类型基因位点突变分别为51、16、43、41例;VHL 1型116例,VHL 2型35例;VHL综合征家族史92例,无VHL综合征家族史59例;合并肾细胞癌127例,合并中枢神经系统病变112例,合并视网膜血管母细胞瘤46例(部分患者合并多种病变)。(3)VHL综合征合并胰腺囊性病变患者的临床病理因素比较:136例VHL综合征合并胰腺囊性病变患者发病年龄,VHL综合征分型(VHL 1型、VHL 2型),合并肾细胞癌分别为32.5(14.0~68.0)岁,110、26例,115例;25例VHL综合征未合并胰腺囊性病变患者上述指标分别为22.0(8.0~64.0)岁,13、12例,14例,两者上述指标比较,差异均有统计学意义(Z=-3.384,χ²=9.770、10.815,P<0.05)。(4)VHL综合征合并pNENs患者的临床病理因素比较:34例VHL综合征合并pNENs患者发病年龄、基因突变位点(外显子1、2、3、其他类型基因位点)、VHL综合征分型(VHL 1型、VHL 2型)分别为33.5(14.0~64.0)岁,12、5、14、3例,18、16例;127例VHL综合征未合并pNENs患者上述指标分别为27.0(9.0~66.0)岁,41、12、32、42例,105、22例;两者上述指标比较,差异均有统计学意义(Z=-4.030,χ²=8.814、13.152,P<0.05)。(5)VHL综合征合并胰腺病变患者的治疗及预后。161例VHL综合征患者中,3例行手术治疗,其余均随访观察。161例VHL综合征患者均获得随访,随访时间为6(1~12)年,其中15例死亡,146例生存(3例手术治疗患者术后分别随访4、14、9年仍生存)。

    结论 

    VHL综合征相关胰腺病变临床影像学特征主要表现为囊性病变及pNENs,以多发病灶为主,多为良性,不需手术干预,预后较好。

    Abstract:
    Objective 

    To investigate the clinical imaging features and prognosis of von Hippel‑Lindau (VHL) syndrome associated with pancreatic lesions.

    Method 

    The retrospective case‑control study was conducted. The clinicopathological data of 161 patients with VHL syndrome who were admitted to Peking University First Hospital from September 2010 to August 2022 were collected. There were 83 males and 78 females, with age of onset as 27.0(range, 8.0-66.0)years. Observation indicators: (1) imaging results of VHL syndrome associated with pancreatic lesions; (2) clinical characteristics of VHL syndrome associated with pancreatic lesions; (3) comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic cystic lesions; (4) comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic neuroendocrine neoplasms (pNENs). (5) Treatment and prognosis of patients with VHL syndrome associated with pancreatic lesions. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the non‑parameter test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi‑square test.

    Results 

    (1) Imaging results of VHL syndrome associated with pancreatic lesions. Of the 161 patients with VHL syndrome, there were 151 patients associated with pancreatic lesions and 10 patients not associated with pancreatic lesions. Of the 151 patients with VHL syndrome associated with pancreatic lesions, there were 136 patient with pancreatic cystic lesions and 34 patients with pNENs, 22 patients with both pNENs and pancreatic cystic lesions, and the type of pancreatic lesions could not be accurately determined in 3 cases. (2) Clinical characteristics of VHL syndrome associated with pancreatic lesions. The age of onset in 151 patients with VHL syndrome associated with pancreatic lesions was 33.0(range, 14.0-68.0)years. Cases with gene site mutation of exon 1, exon 2, exon 3 and other types of gene site was 51, 16, 43 and 41, respectively. There were 116 patients of VHL type 1 and 35 patients of VHL type 2. There were 92 patients with family history of VHL syndrome and 59 patients without family history of VHL syndrome. There were 127 patients combined with renal cell carcinoma, 112 patients combined with central nervous system lesions, 46 patients combined with retinal hemangioblastoma. Patients may combined with multiple lesions. (3) Comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic cystic lesions. The age of onset, VHL syndrome type (VHL1 type, VHL2 type) and cases combined with renal cell carcinoma were 32.5(range, 14.0-68.0)years, 110, 26 and 115 in 136 patients with VHL syndrome associated with pancreatic cystic lesions, versus 22.0(range, 8.0-64.0)years, 13, 12 and 14 in 25 patients with VHL syndrome not associated with pancreatic cystic lesions, showing significant differences in the above indicators between them (Z=-3.384, χ²=9.770, 10.815, P<0.05). (4) Comparison of clinicopathological factors in patients with VHL syndrome associated with pNENs. The age of onset, gene mutation sites (exon 1, exon 2, exon 3, other types of gene site) and VHL syndrome type (VHL1 type, VHL2 type) were 33.5(range, 14.0-64.0)years, 12, 5, 14, 3 and 18, 16 in 34 patients with VHL syndrome associated with pNENs, versus 27.0(range, 9.0-66.0)years, 41, 12, 32, 42 and 105, 22 in 127 patients with VHL syndrome not associated with pNENs, showing significant differences in the above indicators between them (Z=-4.030, χ²=8.814, 13.152, P<0.05). (5) Treatment and prognosis of patients with VHL syndrome associated with pancreatic lesions. Of the 161 patients with VHL syndrome, 3 patients underwent surgical treatment, and the remaining patients were followed up. All 161 patients with VHL syndrome were followed up for 6 (range, 1-12)years, in which 15 patients died and 146 patients alive during the follow‑up. The follow‑up time of 3 patients undergoing surgical treatment was 4, 14, 9 years, respectively, and all of them were alive.

    Conclusions 

    The clinical imaging features of pancreatic lesions related to VHL syndrome are cystic lesions and pNENs, which with the characteristics of multiple lesions and benign tumors. Such patients usually do not requiring surgical treatment and have good prognosis.

  • 陈秋争:设计实验,数据采集整理,统计分析及撰写文章;周靖程:数据采集整理,数据分析,行政、技术、材料支持,数据库维护;刘宗昊:实施研究,采集数据,统计分析;郭小超:分析数据,指导影像学判断;刘伟康:采集、分析数据;田孝东:设计实验,分析数据,对文章的知识性内容作批评性审阅,获取研究经费;龚侃:解释数据,对文章的知识性内容作批评性审阅,获取研究经费,数据库建设;杨尹默:设计实验,分析数据,对文章的知识性内容作批判性审阅,获取研究经费,提供指导和支持
    所有作者均声明不存在利益冲突。
    陈秋争, 周靖程, 刘宗昊, 等. von Hippel‑Lindau综合征合并胰腺病变的临床影像学特征及预后分析[J]. 中华消化外科杂志, 2023, 22(5): 650-656. DOI: 10.3760/cma.j.cn115610-20230417-00172.

    http://journal.yiigle.com/LinkIn.do?linkin_type=cma&DOI=10.3760/cma.j.cn115610-20230417-23172

  • 表  1   VHL综合征合并胰腺囊性病变与未合并胰腺囊性病变患者的临床病理因素比较

    Table  1   Comparison of clinicopathological factors between patients with von Hippel‑Lindau syndrome associated with pancreatic cystic lesions and patients with von Hippel‑Lindau syndrome not associated with pancreatic cystic lesions

    VHL综合征合并胰腺病变情况例数性别(例)发病年龄[M(范围),岁]基因突变位点(例)VHL综合征分型(例)
    外显子1外显子2外显子3其他类型VHL 1型VHL 2型
    合并胰腺囊性病变136686832.5(14.0~68.0)4715344011026
    未合并胰腺囊性病变25151022.0(8.0~64.0)621251312
    统计量值χ²=0.846Z=-3.384χ²=5.478χ²=9.770
    P0.3580.0010.1400.002
    注:VHL为von Hippel‑Lindau
    下载: 导出CSV

    表  2   VHL综合征合并胰腺神经内分泌肿瘤与未合并胰腺神经内分泌肿瘤患者的临床病理因素比较

    Table  2   Comparison of clinicopathological factors between patients with von Hippel‑Lindau syndrome associated with pancreatic neuroendocrine neoplasms and patients with von Hippel‑Lindau syndrome not associated with pancreatic neuroendocrine neoplasms

    VHL综合征合并胰腺病变情况例数性别(例)发病年龄[M(范围),岁]基因突变位点(例)VHL综合征分型(例)
    外显子1外显子2外显子3其他类型VHL 1型VHL 2型
    合并pNENs34132133.5(14.0~64.0)1251431816
    未合并pNENs127705727.0(9.0~66.0)4112324210522
    统计量值χ²=3.061Z=-4.030χ²=8.814χ²=13.152
    P0.080<0.0010.032<0.001
    注:VHL为von Hippel‑Lindau;pNENs为胰腺神经内分泌肿瘤
    下载: 导出CSV
  • [1]

    ChouA, ToonC, PickettJ, et al. Von Hippel‑Lindau syndrome[J]. Front Horm Res,2013,41:30‑49. DOI: 10.1159/000345668.

    [2]

    LonserRR, GlennGM, WaltherM, et al. von Hippel‑Lindau disease[J]. Lancet,2003,361(9374):2059‑2067. DOI:10.10 16/S0140-6736(03)13643-4.

    [3]

    MaherER, IseliusL, YatesJR, et al. Von Hippel‑Lindau disease: a genetic study[J]. J Med Genet,1991,28(7):443‑447. DOI: 10.1136/jmg.28.7.443.

    [4]

    NeumannHP, WiestlerOD. Clustering of features and gene-tics of von Hippel‑Lindau syndrome[J]. Lancet,1991,338(8761):258. DOI: 10.1016/0140-6736(91)90401-a.

    [5]

    VarshneyN, KebedeAA, Owusu‑DapaahH, et al. A review of Von Hippel‑Lindau syndrome[J]. J Kidney Cancer VHL,2017,4(3):20‑29. DOI: 10.15586/jkcvhl.2017.88.

    [6]

    RichardsFM, WebsterAR, McMahonR, et al. Molecular genetic analysis of von Hippel‑Lindau disease[J]. J Intern Med,1998,243(6):527‑533. DOI:10.1046/j.1365-2796.1998.003 34.x.

    [7]

    MaddockIR, MoranA, MaherER, et al. A genetic register for von Hippel‑Lindau disease[J]. J Med Genet,1996,33(2):120‑127. DOI: 10.1136/jmg.33.2.120.

    [8]

    ZhangK, QiuJ, YangW, et al. Clinical characteristics and risk factors for survival in affected offspring of von Hippel⁃Lindau disease patients[J]. J Med Genet,2022,59(10):951-956. DOI: 10.1136/jmedgenet-2021-108216.

    [9]

    ChenF, KishidaT, YaoM, et al. Germline mutations in the von Hippel‑Lindau disease tumor suppressor gene: correlations with phenotype[J]. Hum Mutat,1995,5(1):66‑75. DOI: 10.1002/humu.1380050109.

    [10]

    CharlesworthM, VerbekeCS, FalkGA, et al. Pancreatic lesions in von Hippel‑Lindau disease? A systematic review and meta‑synthesis of the literature[J]. J Gastrointest Surg,2012,16(7):1422‑1428. DOI: 10.1007/s11605-012-1847-0.

    [11]

    TamuraK, NishimoriI, ItoT, et al. Diagnosis and management of pancreatic neuroendocrine tumor in von Hippel-Lindau disease[J]. World J Gastroenterol,2010,16(36):4515-4518. DOI: 10.3748/wjg.v16.i36.4515.

    [12]

    ZbarB, KishidaT, ChenF, et al. Germline mutations in the Von Hippel‑Lindau disease (VHL) gene in families from North America, Europe, and Japan[J]. Hum Mutat,1996,8(4):348‑357. DOI: 10.1002/(SICI)1098-1004(1996)8:4<348::AID-HUMU8>3.0.CO;2-3.

    [13]

    BlansfieldJA, ChoykeL, MoritaSY, et al. Clinical, genetic and radiographic analysis of 108 patients with von Hippel-Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs)[J]. Surgery,2007,142(6):814-818,e1‑e2. DOI: 10.1016/j.surg.2007.09.012.

    [14]

    ChittiboinaP, LonserRR. Von Hippel‑Lindau disease[J]. Handb Clin Neurol,2015,132:139‑156. DOI: 10.1016/B978-0-444-62702-5.00010-X.

    [15]

    BinkovitzLA, JohnsonCD, StephensDH. Islet cell tumors in von Hippel‑Lindau disease: increased prevalence and relationship to the multiple endocrine neoplasias[J]. AJR Am J Roentgenol,1990,155(3):501‑505. DOI:10.2214/ajr. 155.3.1974734.

    [16]

    HammelPR, VilgrainV, TerrisB, et al. Pancreatic involvement in von Hippel‑Lindau disease. The Groupe Francophone d′Etude de la Maladie de von Hippel‑Lindau[J]. Gastroenterology,2000,119(4):1087‑1095. DOI: 10.1053/gast.2000.18143.

图(2)  /  表(2)
计量
  • 文章访问数:  74
  • HTML全文浏览量:  1
  • PDF下载量:  0
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-04-16
  • 网络出版日期:  2024-06-24
  • 刊出日期:  2023-05-19

目录

    /

    返回文章
    返回