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

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

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χ^(2)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,χ^(2)=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,χ^(2)=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。

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,χ^(2)=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,χ^(2)=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.