肝细胞癌癌前结节影像学特征的研究进展

肝细胞癌(HCC)发生是一个多步骤过程,在其发展中检测出HCC癌前病变和进展期HCC,对预测肿瘤行为、判断病变程度、采用最佳治疗策略、改善患者生存至关重要。肝脏成像技术的快速进展和广泛应用,尤其是肝细胞特异性对比剂钆塞酸二钠MRI(Gd-EOB-DTPA MRI)可提供肝结节血管变化、肝细胞功能信息,能够精确区分肝硬化再生结节、低度异型增生结节、高度异型增生结节、早期HCC(early HCC)和HCC,从而进行恶性进展的风险度分层。现综述Gd-EOB-DTPA MRI在HCC早期诊断中的价值,分析HCC多步发展过程中的关键概念,以及癌前病变最终可能转化成典型HCC的影像学表现。     

肝细胞癌癌前异型增生结节的研究现状

异型增生结节(DN)是肝细胞癌(HCC)癌前病变向HCC演变的重要阶段,具有极高的癌变风险。依据细胞异型性的不同,DN可分为低度异型增生结节(LGDN)和高度异型增生结节(HGDN),总结了LGDN与HGDN的病理特点、影像学特征及生物标志物,简述了DN恶变为HCC的风险大小,指出应当提高临床医师对于HCC癌前病变DN的认识,通过对DN的筛查发现恶变风险高的结节并进行干预,以防止HCC的发生。     

肝细胞癌癌前病变的诊断和治疗多学科专家共识( 2020版)

肝癌目前占我国癌症死因的第二位。我国肝癌的发病特点大多遵循乙型肝炎-肝硬化-肝癌的“三步曲”模式。癌前病变的筛查在胃癌、大肠癌和宫颈癌等恶性肿瘤的诊治中已取得了显著的成果。肝硬化状态下的不典型增生结节具有较强的恶变潜能,尤其是高级别不典型增生结节癌变率极高。基于国内外在这一领域的研究成果和专家临床经验,《肝细胞癌癌前病变的诊断和治疗多学科专家共识(2020版)》经多学科协作对肝脏高级别不典型增生结节作为肝癌的癌前病变,从概念、筛查、诊断、治疗和随访等各方面进行了归纳和界定,旨在提出和建立肝癌癌前病变的概念和诊疗原则,为降低我国肝癌的发病率和提高肝癌的总体治疗效果作出贡献。     

肝细胞癌癌前病变的诊断和治疗多学科专家共识(2020版)

肝癌目前占我国癌症死因的第二位。我国肝癌的发病特点大多遵循乙型肝炎-肝硬化-肝癌的"三步曲"模式。癌前病变的筛查在胃癌、大肠癌和宫颈癌等恶性肿瘤的诊治中已取得了显著的成果。肝硬化状态下的不典型增生结节具有较强的恶变潜能,尤其是高级别不典型增生结节癌变率极高。基于国内外在这一领域的研究成果和专家临床经验,《肝细胞癌癌前病变的诊断和治疗多学科专家共识(2020版草案)》经多学科协作对肝脏高级别不典型增生结节作为肝癌的癌前病变,从概念、筛查、诊断、治疗和随访等各方面进行了归纳和界定,旨在提出和建立肝癌癌前病变的概念和诊疗原则,为降低我国肝癌的发病率和提高肝癌的总体治疗效果作出贡献。     

肝细胞不典型增生合并布加综合征误诊为肝细胞癌1例报告

正肝脏不典型增生结节(hepatic dysplastic nodules,HDN),也称为异型增生结节,为肝硬化背景上边界相对清楚的结节样占位性病变。现将1例HDN合并布加综合征(Budd-Chiari syn-drome,BCS)被误诊为肝细胞癌(HCC)患者报道如下。1病例资料患者男性,34岁,因"发现黄疸1个月余"于2019年5月13     

HCC1～2cm不确定结节是否活检?

加拿大一项研究报告,肝脏1～2 cm不确定结节的恶性率较低,对所有这些结节进行活检会导致许多阴性结果,将活检限定于高动脉血供或者同时存在典型HCC的结节则可以检出多数HCC,并且使活检量大大减少。论文发表于《肝脏病学》[Hepatology 2011,54(6):2048]。该研究连续纳入80例患者共计93个不确定的结节,其中85个结节获得最终诊断,包括13个恶性结节和72个良性结节。通过单变量逻辑分析对肝病病因、患者种族、结节大小、高动脉血供、静脉期强化减弱、同时存在典型HCC等因素进行分析,确定能够     

肝脏、胆囊、胆管、胰腺癌前病变的诊断与治疗

前文涉及胃肠道各器官癌前病变的诊断与治疗,本文是其续篇,涉及肝、胆、胰腺癌前病变的诊断与治疗. 1 肝脏的癌前病变 肝脏的异型增生病灶是指存在于肝小叶或硬化结节内<1 mm 的不典型肝细胞群,只有肝活检或切除肝标本的显微镜下才能见到[1].这些不典型肝细胞有小的和大的不典型肝细胞两种,小肝细胞变的胞质减少,呈嗜碱性,胞核有轻度多形性,染色增深,核质比例增加,其中呈扩张型生长者常伴随肝细胞癌存在[2].弥漫性的往往表现为再生肝细胞与再生性改变很难区别.     

胃癌前病变的研究进展

大量研究表明 ,胃癌的发生是一个涉及多个基因改变的多步骤过程。在发生恶性肿瘤之前常经历多年持续的癌前病变 ,目前一致认可的模式为 :慢性萎缩性胃炎→胃粘膜肠化生→胃粘膜不典型增生→胃癌。由于胃癌的病因还不完全清楚 ,实施针对病因的一级预防比较困难 ,因此 ,对癌前病变的研究是胃癌二级预防的重要内容之一。1　胃粘膜不典型增生胃粘膜不典型增生是较为肯定的癌前病变。从胃粘膜不典型增生到癌变并非是一个必然过程 ,轻、中、重度不典型增生之间可以相互转化 ,也都可以发生癌变。相对而言 ,重度不典型增生发生逆转的机率小 ,更容易…     

肝再生大结节与早期肝癌

肝细胞再生大结节(Macroregenerative Nodule,MRN)又称异型结节,过去曾称为肝腺瘤样增生。先是日本学者在80年代中期发现一些原疑为肝癌的肝内小结节经镜检发现并非肝癌。这些结节内细胞形态及排列可异型也可不异型,结内有时可见微小肝癌灶,提示它们与早期肝癌(HCC)的发生密切相关。以后欧     

中医药防治肝癌研究进展

近年来 ,大量的实验与临床研究表明 ,中医药有阻断 HCC癌前病变、抑制癌细胞增殖、诱导癌细胞凋亡、抑制癌基因表达等作用 ,中药对原发性肝细胞癌 ( HCC)及其并发症有较好的疗效 ,本文就中医药防治 HCC的研究进展作一综述。1　中医药阻断癌前病变 ,预防 HCC发生的研究肝细胞癌变不外乎基因突变和基因调控失常两种途径 ,其过程大致为肝组织破坏、细胞增生、癌变。目前中药阻断癌前病变 ,预防 HCC发生的研究思路 ,大致按上述途径及过程可归纳为 :1抗基因突变。应用血清药理学研究中药抗突变的结果表明 ,山楂、当归、丹参、五味子、女贞…     

MR with Gd-EOB-DTPA in assessment of liver nodules in cirrhotic patients

To date the imaging diagnosis of liver lesions is based mainly on the identification of vascular features, which are typical of overt hepatocellular carcinoma(HCC), but the hepatocarcinogenesis is a complex and multistep event during which, a spectrum of nodules develop within the liver parenchyma, including benign small and large regenerative nodule(RN), low-grade dysplastic nodule(LGDN), high-grade dysplastic nodule(HGDN), early HCC, and well differentiated HCC. These nodules may be characterised not only on the basis of their respective different blood supplies, but also on their different hepatocyte function. Recently, in liver imaging the introduction of hepatobiliary magnetic resonance imaging contrast agent offered the clinicians the possibility to obtain, at once, information not only related to the vascular changes of liver nodules but also information on hepatocyte function. For this reasons this new approach becomes the most relevant diagnostic clue for differentiating low-risk nodules(LGDN-RN) from highrisk nodules(HGDN/early HCC or overt HCC) and consequently new diagnostic algorithms for HCC have been proposed. The use of hepatobiliary contrast agents is constantly increasing and gradually changing the standard of diagnosis of HCC. The main purpose of this review is to underline the added value of Gd-EOB-DTPA in early-stage diagnoses of HCC. We also analyse the guidelines for the diagnosis and management of HCC, the key concepts of HCC development, growth and spread and the imaging appearance of precursor nodules that eventually may transform into overt HCC.     

Multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated hepatocellular carcinoma in a patient with alcohol-related liver cirrhosis

We describe a rare case of the transformation of a dysplastic nodule into well-differentiated hepato- cellular carcinoma (HCC) in a 56-year-old man with alcoholrelated liver cirrhosis. Ultrasound (US) disclosed a 10 mm hypoechoic nodule and contrast enhanced US revealed a hypovascular nodule, both in segment seven. US-guided biopsy revealed a high-grade dysplastic nodule characterized by enhanced cellularity with a high N/C ratio, increased cytoplasmic eosinophilia, and slight cell atypia. One year later, the US pattern of the nodule changed from hypoechoic to hyperechoic without any change in size or hypovascularity. US-guided biopsy revealed well-differentiated HCC of the same features as shown in the first biopsy, but with additional pseudoglandular formation and moderate cell atypia. Moreover, immunohistochemical staining of cyclase- associated protein 2, a new molecular marker of well- differentiated HCC, turned positive. This is the first case of multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated HCC within one year in alcohol-related liver cirrhosis.     

磁共振磁敏感加权成像在肝硬化结节多步癌变中的临床应用

肝癌早期发现,早期治疗,明显提高5年生存率。肝硬化患者,绝大部分均经历肝硬化结节多步癌变的过程,即由再生结节发展为异型增生结节,其中高分化异型增生结节发展为癌变结节后（早期肝癌）,再发展为小肝癌,小肝癌最后发展成进展期或晚期肝癌。上述结节的一系列变化过程中,其结节内内源性铁逐步廓清,本文重点介绍利用磁共振磁敏感加权成像（SWI）技术观察结节中内源性铁变化情况,同时结合常规MRT2W1、弥散加权成像（DWI）和动态增强等技术,提高识别肝硬化背景下的癌变／早期肝癌结节能力,从而对进一步提高早期小肝癌的诊疗,具有更重要的临床意义。     

Serum amyloid A and C‐reactive protein positive nodule in alcoholic liver cirrhosis,hard to make definite diagnosis

We describe a case of serum amyloid A (SAA) and C‐reactive protein (CRP) positive nodule detected by immunohistochemical analysis in a 37‐year‐old woman with alcohol‐related cirrhosis. Imaging studies at first admission pointed to hepatocellular carcinoma (HCC), a dysplastic nodule, an inflammatory pseudotumor or focal nodular hyperplasia (FNH). Ultrasonography‐guided biopsy in Segment 2 showed minimal atypical changes, except for a slight increase in cell density and micronodular cirrhosis in the non‐nodular portion. gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid‐enhanced magnetic resonance imaging carried out after a year and a half revealed hypervascularity in the arterial phase and isointensity in the hepatobiliary phase. Three years thereafter, however, the imaging displayed a change from isointensity to a defect in the hepatobiliary phase, and the nodule demonstrated minimal histological atypia. Immunohistochemical staining of the nodule was positive for SAA, CRP, liver fatty acid‐binding protein and glutamine synthetase, but negative for β‐catenin, heat shock protein 70 and Glypican 3. Organic anion transporter (OATP)8 staining was weaker in the nodule than in the non‐nodular portion of the alcohol‐related micronodular cirrhosis. The nodule was diagnosed as an SAA and CRP positive nodule, and HCC was ruled out. Despite the change from isointensity to a defect in the hepatobiliary phase, no evidence of HCC was found in the biopsy specimen. The change may be explained more by the weak OATP8 staining compared with that of alcohol‐related liver cirrhosis than by malignant transformation into HCC.     

The vascular profile of regenerative and dysplastic nodules of the cirrhotic liver: implications for diagnosis and classification.

We investigated the angiogenic phenotype of regenerative and dysplastic hepatocellular nodules to assess whether these lesions have distinct vascular profiles compared with the adjacent nonneoplastic or malignant liver. Forty-three liver nodules surgically removed from 18 patients were classified into regenerative and dysplastic categories. Serial sections of each nodule, adjacent cirrhotic liver (16 patients), and associated hepatocellular carcinoma (HCC) (6 patients), have been immunostained against CD31 and alpha-smooth muscle actin (alphaSMA) to detect capillary and muscular vessels. The study included 20 large regenerative nodules (LRNs), 13 low-grade dysplastic nodules (LGDNs), and 10 high-grade dysplastic nodules (HGDNs). The number of both capillary units and unpaired arteries was significantly increased in HGDNs and malignant lesions over LGDNs, regenerative, and cirrhotic nodules (P <.01), which showed an overlapping vascular profile. In addition, the number of capillary units, but not that of unpaired arteries, was significantly increased in HCC compared with HGDNs (P <.01). These results show that certain angiogenic features segregate HGDNs from other nonmalignant nodules such as LRNs and LGDNs. The former group of lesions is similar to HCC whereas the latter group is undistinguishable from the adjacent cirrhosis as far as their vascular profile is concerned. The adopted investigative approach does not support the morphological distinction between LRNs and LGDNs although it suggests that HGDNs are likely advanced precursors of HCC. An abnormal number of capillary units and/or unpaired arteries in a nonmalignant hepatocellular nodule can be diagnostically helpful to identify a precancerous lesion.     

Differentiation between dysplastic nodule and early-stage hepatocellular carcinoma: The utility of conventional MR imaging

AIM:To elucidate the variety of ways early-stage hepatocellular carcinoma(HCC)can appear on magnetic resonance(MR)imaging by analyzing T1-weighted,T2-weighted,and gadolinium-enhanced dynamic studies.METHODS:Seventy-three patients with well-differentiated HCC(wHCC)or dysplastic nodules were retrospectively identified from medical records,and new histological sections were prepared and reviewed.The tumor nodules were categorized into three groups:dysplastic nodule(DN),wHCC compatible with Edmondson-Steiner grade I HCC(w1-HCC),and wHCC compatible with Edmondson-Steiner gradeⅡHCC(w2-HCC).The signal intensity on pre-contrast MR imaging and the enhancing pattern for each tumor were recorded and compared between the three tumor groups.RESULTS:Among the 73 patients,14 were diagnosed as having DN,40 were diagnosed as having w1-HCC,and 19 were diagnosed as having w2-HCC.Hyperintensity measurements on T2-weighted axial images(T2WI)were statistically significant between DNs and wHCC(P=0.006)and between DN and w1-HCC(P=0.02).The other imaging features revealed no significant differences between DN and wHCC or between DN and w1-HCC.Hyperintensity on both T1W out-phase imaging(P=0.007)and arterial enhancement on dynamic study(P=0.005)showed statistically significant differences between w1-HCC and w2-HCC.The other imaging features revealed no significant differences between w1-HCC and w2-HCC.CONCLUSION:In the follow-up for a cirrhotic nodule,increased signal intensity on T2WI may be a sign of malignant transformation.Furthermore,a noted loss of hyperintensity on T1WI and the detection of arterial enhancement might indicate further progression of the histological grade.     

Detection of nodules in liver cirrhosis: spiral computed tomography or magnetic resonance imaging? A prospective study of 88 nodules in 34 patients

Detection and characterization of all focal lesions in the liver are critical for screening patients with chronic liver disease. The aim of this prospective study was to investigate the accuracy of magnetic resonance imaging (MRI) and spiral computed tomography for the diagnosis of hepatic nodules in cirrhotic patients when compared with pathological findings of the explanted liver. From February 1997 to July 1999, 34 cirrhotic patients waiting for orthotopic liver transplantation (OLT) (mean age, 53.5 +/- 9.3 years; 24 males) were included. All patients had MRI and spiral computed tomography examinations, and findings were matched with the histological findings. Data analyses were made using the McNemar chi-square test. Mean time between radiological examination (MRI or spiral computed tomography) and OLT was 43.8 +/- 39 days. A total of 88 nodules were found in the 34 patients: 54 hepatocellular carcinoma (HCC) (mean size, 18 +/- 10 mm) in 21 patients, 22 dysplastic nodules (mean size, 10.7 +/- 4.3 mm) in 11 patients, and 12 macroregenerative nodules in 13 patients. Lesion-by-lesion analyses showed that sensitivity of MRI and spiral computed tomography for nodule, HCC or dysplastic nodule diagnosis was 44.3 and 31.8% (P = 0.02), 61.1 and 51.9% (P = 0.2), and 27.3 and 0% (P = 0.04), respectively. Patient-by-patient analyses showed no statistical difference between spiral computed tomography and MRI for nodule diagnosis. In conclusion, in patients with liver cirrhosis, MRI is more accurate than spiral computed tomography for the detection of liver nodules and dysplastic nodules. However, tumour size is always a restricting factor for these two techniques, which are unable to detect small HCC in more than 60% of cases.     

Accuracy and disagreement of computed tomography and magnetic resonance imaging for the diagnosis of small hepatocellular carcinoma and dysplastic nodules: role of biopsy

Liver macronodules, ranging from benign to low-grade or high-grade dysplastic nodules (LGDNs/HGDNs) and hepatocellular carcinoma (HCC), may develop during chronic liver diseases (CLDs). Current guidelines were recently updated and the noninvasive criteria for the diagnosis of small HCC are based on a single typical radiological pattern and nonconclusive coincidental findings with two techniques. This study aimed to assess the accuracy and disagreements of noninvasive multiphasic examinations for the diagnosis of HCC and dysplastic nodules (DNs) and the role of biopsy. Seventy-four consecutive patients with CLD with ultrasound-detected 1-2-cm nodules underwent, within 1 month, multiphasic computed tomography (CT), magnetic resonance imaging (MRI), and biopsy of the nodule. Median age was 60 years; 33 patients (45%) had hepatitis C virus, 20 (27%) had hepatitis B virus, and 13 (18%) patients had no cirrhosis. Biopsy revealed 47 HCCs, 6 HGDNs, 1 LGDNs, 1 cholangiocarcinoma, and 1 epithelioid hemangioendothelioma. There were no tumors in the other 18 patients. All patients (31 of 31; 100%) who had conclusive coincidental findings (i.e., arterial enhancement and washout) on both examinations had HCC or HGDN (sensitivity, 57%; specificity, 100%). All patients (51 of 51; 100%) who had conclusive findings on at least one of the two examinations had HCC or HGDN (sensitivity, 96%; specificity, 100%). There was a disagreement regarding imaging findings between CT and MRI in 21 of 74 (28%) patients and no washout on both examinations in 23 of 74 patients (31%). In these 44 patients, liver biopsy provided an initial accurate diagnosis. CONCLUSION: The noninvasive diagnosis of HCC or HGDN can be obtained if arterial enhancement and washout are found in a single dynamic imaging examination. These findings are frequently discordant on both CT and MRI, supporting the place of biopsy for the diagnosis of small HCCs.     

Combined treatment of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates hepatic dysplastic nodule in a patient with liver cirrhosis

Although it is well known that the hepatocellular carcinoma (HCC) is an ominous complication in patients with liver cirrhosis, there has been no approved drug to prevent the development of HCC to date. We previously reported that the combined treatment of vitamin K2 (VK) and angiotensin-converting enzyme inhibitor (ACE-I) significantly suppressed the experimental hepatocarcinogenesis. A 66-year-old Japanese woman with hepatitis C virus (HCV)-related liver cirrhosis developed a dysplastic nodule in the liver detected by enhanced computed tomography along with elevation of the tumor markers, namely, alpha-fetoprotein (AFP) and lectin-reactive demarcation (AFP-L3), suggesting the presence of latent HCC. After oral administration of VK and ACE-I, the serum levels of both AFP and AFP-L3 gradually decreased without any marked alteration of the serum aminotransferase activity. After one-year treatment, not only the serum levels of AFP and AFP-L3 returned to the normal ranges, but also the dysplastic nodule disappeared. Since both VK and ACE-I are widely used without serious side effects, this combined regimen may become a new strategy for chemoprevention against HCC.