Abstract
胰腺癌是一种高度恶性肿瘤,手术切除是唯一可能治愈的方法。为提高胰腺癌患者的预后,胰腺癌的早期精准诊断与评估非常重要。影像学检查在胰腺癌的发现、肿瘤分期、可切除性评估等方面起重要作用,可以为胰腺癌的诊治提供可靠依据。目前常用于胰腺癌的影像学检查包括常规超声、超声内镜、PET-CT、多层螺旋CT(MDCT)以及磁共振等,不同的影像学检查具有各自的特点,其中MDCT和磁共振应用最广泛。本文对影像学在胰腺癌的精准诊断和评估中的应用研究进展进行综述。
Abstract
Pancreatic cancer is a highly malignant tumor and surgical resection is the only curative treatment option. In order to improve the prognosis of patients with pancreatic cancer, it is very important to diagnose and evaluate pancreatic cancer accurately and early. Imaging examinations play an important role in tumor detection, staging and surgical resectability evaluation, which can provide reliable evidences for diagnosis and treatment of pancreatic cancer. At present, the imaging techniques commonly used for diagnosis of pancreatic cancer include conventional ultrasound, endoscopic ultrasonography, PET-CT, multi-detector row CT (MDCT), magnetic resonance imaging (MRI), in which MDCT and MRI are the most widely used. In this article, the application and research progress of imaging in accurate diagnosis and evaluation of pancreatic cancer are reviewed.
Keywords: Pancreatic neoplasms/pathology; Pancreatic neoplasms/diagnosis; Pancreatic neoplasms/surgery; Tomography, spiral computed; Magnetic resonance imaging; Neoplasm staging; Prognosis; Review
胰腺癌是病死率极高的消化系统恶性肿瘤,患者五年存活率不超过6% [ 1] 。胰腺位于腹膜后,位置隐匿,再加上胰腺癌早期缺乏典型症状,极易漏诊和误诊。血清肿瘤标志物如CA199对胰腺癌具有一定的提示作用,但其敏感度和特异度均不高,针对早期胰腺癌的诊断效率更低 [ 2] 。近年来,影像学在胰腺癌诊断中的价值成为研究的热点。常规超声操作方便、无创、价格低廉,但由于易受操作者及胃肠道气体影响,对胰腺癌的诊断效率较低;超声内镜被用于小胰腺癌的诊断和胰腺癌的分期,但属于侵入性操作,并非胰腺癌诊断的首选方法;PET-CT在检查胰腺癌转移方面具有独特的优势 [ 3] ,但检查费用昂贵。目前,胰腺癌诊断中应用最广泛的影像学检查方法是多层螺旋CT(multi-detector row CT, MDCT)和磁共振。MDCT具有较好的空间和时间分辨率,扫描范围大,并可对图像进行各种后处理;磁共振具有更高的软组织分辨率,其多序列、多参数成像的特点可为胰腺癌的诊断提供更全面的信息。本文对近年来影像学方法在胰腺癌的精准诊断和评估中应用的研究进展进行综述。
直接征象:典型的胰腺癌在CT平扫图像上常表现为等密度或稍低密度,增强扫描强化程度较胰腺实质低;在磁共振T 1加权像(T 1WI)上大多表现为低信号,少数呈等信号,T 2加权像(T 2WI)上可呈等信号、低信号或稍高信号;二乙烯三胺五乙酸钆(Gd-DTPA)增强扫描早期大多数胰腺癌的信号强度都低于胰腺实质,增强后期信号强度可接近邻近胰腺实质。
间接征象:①胰腺轮廓改变:当胰腺癌体积较大时,可引起胰腺轮廓改变,表现为胰腺局限性膨大或肿块突出于胰腺轮廓外。②癌肿远端胰腺萎缩:由于血供异常等原因,肿瘤远端胰腺常萎缩。③胰、胆管截断征:当癌肿引起胰、胆管阻塞时,表现为胰、胆管突然中断。④双管征:当癌肿阻塞胰管和胆管,引起两者均扩张,称为“双管征” [ 4] ,以胰头癌多见。⑤继发潴留囊肿:当癌肿破坏胰腺导管引起胰液外溢并积聚于胰腺组织内形成囊肿,常位于胰腺远端,也可见于胰周间隙。
虽然胰腺癌的总体预后差,但肿瘤直径小于1 cm的患者如及时行手术切除,其五年存活率高达100% [ 5] 。然而,据文献报道,由于早期胰腺癌的检出率极低, 小于1 cm的胰腺癌只占手术切除病例的0.55% [ 6] 。在MDCT上胰腺癌常表现为缺乏血供的低密度肿块,增强扫描其强化程度低于正常胰腺实质,但有10%~14%的肿瘤在平扫及增强扫描时均表现为等密度 [ 7] ,这类肿瘤组织病理学上往往是高分化的肿瘤,基质中纤维组织较疏松,并可见萎缩变性的腺体组织。早期胰腺癌由于分化较好,表现为等密度的比例更高,容易漏诊。要准确诊断表现为等密度的早期胰腺癌,需密切关注胰腺癌的间接征象。据报道,88%直径小于2 cm的等密度胰腺癌伴随间接征象,其中胰管截断征的发生率约为59%,双管征的发生率约为63%,胰腺萎缩的发生率约为21% [ 8] 。因此,当MDCT观察到上述征象但未发现肿瘤时,应行进一步检查以明确诊断。磁共振有扩散加权成像、动态增强扫描、磁共振胰胆管造影等多个序列,有报道称T 1WI脂肪抑制和动态增强扫描是检测胰腺癌最敏感的方法 [ 9] ,多序列联合可显著提高早期胰腺癌诊断的敏感度和特异度 [ 10] 。超声内镜近年来也较多地用于胰腺癌的诊断,目前认为是小胰腺癌诊断的重要方法,在胰腺癌的分期上也具有重要作用 [ 11] ,同时还可在超声内镜下行穿刺细胞学检查。但其属于侵入性操作,并非诊断胰腺癌的首选方法。
胰腺癌常合并慢性胰腺炎,后者是前者的高危因素,两者均易发生于胰头,且临床及影像学表现相似,尤其是慢性局灶性胰腺炎与胰腺癌的鉴别存在困难。钙化灶、胰管扩张、局部肿物、双管征、胰胆管截断、周围脂肪浸润、胰腺外周静脉阻塞等影像学表现在胰腺癌与慢性局灶性胰腺炎中均可出现。但是,与胰腺癌相比,慢性局灶性胰腺炎患者血清肿瘤标志物多处于正常范围,常有急慢性胰腺炎病史,伴轻度胰腺萎缩,病灶密度(信号)均匀,呈渐进性强化,具有胆、胰管不扩张或胰管穿通征、胰周纤维条索灶等征象。其中,胰管穿通征对两者的鉴别诊断具有重要的价值,此征象利用磁共振胰胆管造影最易观察 [ 12- 13] 。
胰腺弥漫性脂肪浸润多见于老年人和肥胖者,但局灶性脂肪浸润相对少见,一般好发于胰头和钩突 [ 14- 15] 。部分脂肪浸润较轻的病例CT平扫时表现不明显,增强扫描时可见病灶处密度低于周围胰腺组织,容易被误诊为胰腺癌 [ 16] 。利用磁共振化学位移成像技术可判断病灶内存在的少量脂质成分,从而明确胰腺局灶性脂肪浸润的诊断 [ 14] 。
2%的急性胰腺炎患者伴有胰腺癌 [ 17] ,而6.8%~13.8%的胰腺癌患者伴有急性胰腺炎 [ 18] 。当胰腺癌继发急性胰腺炎、造成潴留囊肿或胰管明显扩张而未见肿块时,由于继发性病变在影像学上表现明显,甚至掩盖原发病灶表现,因此在观察上述征象时,需要谨慎诊断,避免漏诊。
目前,手术切除是唯一可能根治胰腺癌的方案,但胰腺癌早期缺乏典型症状,多数患者发现时已有远处转移,仅有15%~20%的患者可能获得手术机会 [ 19] 。因此,准确判断胰腺癌的可切除性,对胰腺癌治疗方案的选择具有重要意义。
不同学者对胰腺癌胰周血管侵犯的影像学标准提出了不同的观点 [ 20- 24] ,目前较为统一的胰腺癌可切除性评估标准为美国国家综合癌症网络(NCCN)胰腺癌临床实践指南提供的胰腺癌手术可切除性评估指南。在2016年第2版的基础上,2017年第1版的NCCN胰腺癌临床实践指南对“可能切除”的动脉侵犯标准稍作了修改( 表 1)。将胰头或钩突肿瘤可能切除的动脉侵犯标准中“变异动脉的存在”修改为“肿瘤与变异动脉接触”;在胰体尾肿瘤可能切除的动脉侵犯标准“肿瘤与肠系膜上动脉接触不超过180°,但不侵犯主动脉,且胃十二指肠动脉完整不受侵犯”中添加了“可施行改良Appleby手术”。同时,2017年第1版指南还强调了增强CT和磁共振在胰腺癌评估中的重要性。
表1 2017年第1版美国国家综合癌症网络胰腺癌手术可切除性评估指南摘要
Table 1 National Comprehensive Cancer Network guidelines version 1.2017 (pancreatic adenocarcinoma): criteria defining resectibility status
可切除性 |
动脉 |
静脉 |
可切除 |
肿瘤未与腹腔干、肠系膜上动脉或肝总动脉接触 |
肿瘤未与肠系膜上静脉、门静脉接触或接触不超过180°且血管轮廓光整 |
可能切除 |
胰头或钩突 肿瘤与肝总动脉接触但未扩展到腹腔干或肝动脉分叉,允许安全完整切除并重建 肿瘤与肠系膜上动脉接触不超过180° 肿瘤与变异动脉接触(比如副肝右动脉、替代肝右动脉、替代肝总动脉,以及这些替代动脉或副动脉的起源动脉)接触的程度应予以指出,因为可能会影响到手术计划 胰体尾肿瘤与腹腔干接触不超过180° 肿瘤与肠系膜上动脉接触不超过180°,但不侵犯主动脉,且胃十二指肠动脉完整不受侵犯可施行改良Appleby手术(部分学者倾向于这个标准在“不可切除”范围内) 远处转移(包括非区域淋巴结转移) |
肿瘤与门静脉、肠系膜上静脉接触超过180°;或接触不超过180°且血管轮廓不光整;或静脉内有血栓形成但血管可安全切除或重建肿瘤与下腔静脉接触 |
不可切除 |
胰头或钩突 肿瘤包绕肠系膜上动脉超过180° 肿瘤包绕腹腔干超过180° 侵犯肠系膜上动脉第一空肠支胰体尾 肿瘤包绕肠系膜上动脉或腹腔干超过180° 肿瘤侵及腹腔干及腹主动脉 |
胰头或钩突 肠系膜上静脉或门静脉因受侵或栓塞(可能为瘤栓或血栓)无法重建 肿瘤侵犯多数近端引流空肠静脉至肠系膜上静脉胰体尾 肠系膜上静脉或门静脉因受侵或栓塞(可能为瘤栓或血栓)无法重建 |
高质量的影像是准确评估胰腺癌与临近血管之间关系的首要条件。胰腺周围结构复杂,血供丰富,MDCT血管造影可明显提高空间分辨率,有多种重建技术如多平面重建、曲面重建、最大密度投影及容积重建等,可清晰显示胰腺癌与临近血管之间的关系,从不同角度观察肿瘤是否与血管接触、包绕,血管腔是否狭窄、堵塞及其程度与范围,是评估胰腺癌胰周血管侵犯的重要手段,弥补了过去仅靠横断位影像不易观察受侵血管全貌的不足,为评估手术切除可能性提供重要信息。
磁共振在评估肿瘤可切除性方面具有与CT相似的敏感度和特异度 [ 25] ,但检查费用高,扫描时间长,并不作为胰腺癌评估的首选影像学检查方法。目前,磁共振主要用于胰腺癌肝脏转移灶、CT上表现为等密度的肿瘤或存在增强CT检查禁忌的患者,为胰腺癌可切除性评估提供补充信息。
影像学评估胰腺癌可切除性对治疗方案的选择具有指导意义,但也存在一些问题。“可能切除的胰腺癌”经新辅助治疗后进展停滞甚至降期,有学者指出,影像学检查并不能准确反映此类肿瘤的真实进展 [ 26- 27] 。其原因是经新辅助治疗后肿瘤及正常胰腺组织发生纤维化,血管周围表现为模糊影或脂肪条缩影,而目前的影像学检查难以鉴别纤维组织与存活的肿瘤,影响了肿瘤可切除性评估的准确性 [ 28- 29] 。
准确的胰腺癌TNM分期可指导治疗方案的选择,评估患者预后。美国癌症联合委员会(AJCC)癌症分期系统是目前应用最广泛的肿瘤分期系统。AJCC第8版胰腺癌分期系统对第7版存在的问题进行了修订,取消了“肿瘤浸润至胰腺外”的表述;用肿瘤最大径区分T1、T2、T3期,并将T1期分为T1a(肿瘤最大径不超过0.5 cm)、T1b(肿瘤最大径超过0.5 cm且小于1 cm)、T1c(肿瘤最大径不小于1 cm且不超过2 cm);T4期取消了“肿瘤不可切除”,添加了“肝总动脉受侵犯”标准;将区域淋巴结转移情况分为N0:无区域淋巴结转移, N1:1~3枚区域淋巴结转移, N2:4枚及以上区域淋巴结转移。从影像学角度来看,新的T分期系统更客观,重复性更好,但也给放射科医师带来了一定的挑战。
MDCT可显示肿瘤形态学特征、邻近血管侵犯、淋巴结及远处转移,从而实现对胰腺癌TNM分期的评估。但MDCT也存在一定的缺陷,它对不同大小的肿瘤敏感度不同,其对于直径超过2 cm的肿瘤敏感度为90%~98%,而对于较小的肿瘤敏感度降至60%~77% [ 30] 。因此,MDCT对于T1期肿瘤的发现以及进一步分期存在困难。磁共振拥有多序列成像,对小胰腺癌的诊断优于MDCT。此外,MDCT对于转移淋巴结的诊断缺乏统一标准,仅仅依靠形态学改变无法准确判断淋巴结转移与否。磁共振扩散加权成像是一种功能成像技术,同时具备解剖成像和功能成像特点,可显示淋巴结代谢改变,结合淋巴结的表观弥散系数(ADC)可帮助诊断转移性淋巴结 [ 31] 。PET-CT依据淋巴结摄取氟脱氧葡萄糖(18F-FDG)的高低进行定性诊断,其诊断的敏感度和特异度也优于MDCT [ 32] 。此外,运用磁共振靶向淋巴管成像技术、影像组学诊断转移性淋巴结等也在研究进程中,未来对转移性淋巴结的诊断将会更精确。
胰腺癌进展快,首诊时即可伴随远处转移,最常见的远处转移为肝脏 [ 33] 。磁共振具有较高的软组织分辨率和多种成像技术,对于肝脏转移性小病灶的检测优于MDCT [ 34] ,尤其是肝细胞特异性对比剂钆塞酸二钠(Gd-EOB-DTPA,普美显)可明显提高肝脏转移灶的检出率 [ 35- 36] 。PET-CT扫描范围广,可用于怀疑全身转移的患者,对于腹腔内肝外转移灶显示较好,但对于肝脏内小于1 cm的转移灶的敏感度低 [ 37] ,对于胰腺癌分期的价值有限。
综上所述,胰腺癌的影像学诊断虽有一定规律可循,但各种影像学检查方法具有各自不同的特点。分子影像学的不断发展使得提高胰腺癌影像学诊断的敏感度和特异度成为可能。筛选出敏感度和特异度高的标志物及其配体并研制适用的靶向对比剂是目前胰腺癌分子影像学的主要研究方向。相信针对胰腺癌的分子影像学研究将对胰腺癌的诊断和治疗产生深远影响。
Funding Statement
浙江省胰腺癌综合诊治科技创新团队计划(2013TD06)
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