The discontinuous peripheral enhancement is a pattern of enhancement usually attributed to typical cavernous hemangioma, that is the most common benign solid lesion of the liver. The discontinuous peripheral enhancement, however, may be encountered in many other benign and malignant focal liver lesions as an atypical presentation or evolution, and hemangiomas with discontinuous peripheral hyperenhancement on hepatic arterial phase may not always have the typical post-contrast pattern on portal venous and delayed phases. Therefore, abdominal radiologists may be challenged in their practice by lesions with discontinuous peripheral enhancement. This pictorial essay aims to review the spectrum of benign and malignant focal liver lesions that may show discontinuous peripheral enhancement. A particular point of interest is the diagnostic tree pathway that may guide the radiologists in the differential diagnosis.

Dieldrin is an organochlorine insecticide that was widely used until 1970 when its use was banned because of its liver carcinogenicity in mice. Several long-term rodent bioassays have reported dieldrin to induce liver tumors in in several strains of mice, but not in rats. This article reviews the available information on dieldrin liver effects and performs an analysis of mode of action (MOA) and human relevance of these liver findings. Scientific evidence strongly supports a MOA based on CAR activation, leading to alterations in gene expression, which result in increased hepatocellular proliferation, clonal expansion leading to altered hepatic foci, and ultimately the formation of hepatocellular adenomas and carcinomas. Associative events include increased liver weight, centrilobular hypertrophy, increased expression of Cyp2b10 and its resulting increased enzymatic activity. Other associative events include alterations of intercellular gap junction communication and oxidative stress. Alternative MOAs are evaluated and shown not to be related to dieldrin administration. Weight of evidence shows that dieldrin is not DNA reactive, it is not mutagenic, and it is not genotoxic in general. Furthermore, activation of other pertinent nuclear receptors, including PXR, PPARα, AhR, and estrogen are not related to dieldrin-induced liver tumors nor is there liver cytotoxicity. In previous studies, rats, dogs, and non-human primates did not show increased cell proliferation or production of pre-neoplastic or neoplastic lesions following dieldrin treatment. Thus, the evidence strongly indicates that dieldrin-induced mouse liver tumors are due to CAR activation and are specific to the mouse, which are qualitatively not relevant to human hepatocarcinogenesis. Thus, there is no carcinogenic risk to humans. This conclusion is also supported by a lack of positive epidemiologic findings for evidence of liver carcinogenicity. Based on current understanding of the mode of action of dieldrin-induced liver tumors in mice, the appropriate conclusion is that dieldrin is a mouse specific liver carcinogen and it does not pose a cancer risk to humans.

Rim arterial phase hyperenhancement is an imaging feature commonly encountered on contrast-enhanced CT and MRI in focal liver lesions. Rim arterial phase hyperenhancement is a subtype of arterial phase hyperenhancement mainly present at the periphery of lesions on the arterial phase. It is caused by a relative arterialization of the periphery compared with the center of the lesion and needs to be differentiated from other patterns of peripheral enhancement, including the peripheral discontinuous nodular enhancement and the corona enhancement. Rim arterial phase hyperenhancement may be a typical or an atypical imaging presentation of many benign and malignant focal liver lesions, challenging the radiologists during imaging interpretation. Benign focal liver lesions that may show rim arterial phase hyperenhancement may have a vascular, infectious, or inflammatory origin. Malignant focal liver lesions displaying rim arterial phase hyperenhancement may have a vascular, hepatocellular, biliary, lymphoid, or secondary origin. The differences in imaging characteristics on contrast-enhanced CT may be subtle, and a multiparametric approach on MRI may be helpful to narrow the list of differentials. This article aims to review the broad spectrum of focal liver lesions that may show rim arterial phase hyperenhancement, using an approach based on the benign and malignant nature of lesions and their histologic origin. CRITICAL RELEVANCE STATEMENT: Rim arterial phase hyperenhancement may be an imaging feature encountered in benign and malignant focal liver lesions and the diagnostic algorithm approach provided in this educational review may guide toward the final diagnosis. KEY POINTS: Several focal liver lesions may demonstrate rim arterial phase hyperenhancement. Rim arterial phase hyperenhancement may occur in vascular, inflammatory, and neoplastic lesions. Rim arterial phase hyperenhancement may challenge radiologists during image interpretation.

OBJECTIVE: Detection of liver metastases is crucial for guiding oncological management. Computed tomography through iterative reconstructions is widely used in this indication but has certain limitations. Deep learning image reconstructions (DLIR) use deep neural networks to achieve a significant noise reduction compared to iterative reconstructions. While reports have demonstrated improvements in image quality, their impact on liver metastases detection remains unclear. Our main objective was to determine whether DLIR affects the number of detected liver metastasis. Our secondary objective was to compare metastases conspicuity between the two reconstruction methods.
METHODS: CT images of 121 patients with liver metastases were reconstructed using a 50% adaptive statistical iterative reconstruction (50%-ASiR-V), and three levels of DLIR (DLIR-low, DLIR-medium, and DLIR-high). For each reconstruction, two double-blinded radiologists counted up to a maximum of ten metastases. Visibility and contour definitions were also assessed. Comparisons between methods for continuous parameters were performed using mixed models.
RESULTS: A higher number of metastases was detected by one reader with DLIR-high: 7 (2-10) (median (Q₁-Q₃); total 733) versus 5 (2-10), respectively for DLIR-medium, DLIR-low, and ASiR-V (p < 0.001). Ten patents were detected with more metastases with DLIR-high simultaneously by both readers and a third reader for confirmation. Metastases visibility and contour definition were better with DLIR than ASiR-V.
CONCLUSIONS: DLIR-high enhanced the detection and visibility of liver metastases compared to ASiR-V, and also increased the number of liver metastases detected.
UNASSIGNED: Deep learning-based reconstruction at high strength allowed an increase in liver metastases detection compared to hybrid iterative reconstruction and can be used in clinical oncology imaging to help overcome the limitations of CT.
CONCLUSIONS: Detection of liver metastases is crucial but limited with standard CT reconstructions. More liver metastases were detected with deep-learning CT reconstruction compared to iterative reconstruction. Deep learning reconstructions are suitable for hepatic metastases staging and follow-up.

Objective: To explore the magnetic resonance imaging (MRI) features and classification of intraductal papillary neoplasm of the bile duct (IPNB). Methods: Data from 90 patients with intraductal papillary neoplasm of the bile duct confirmed pathologically between June 2010 and January 2023 were retrospectively analyzed. The image analysis included the shape and location of the tumor, whether bile ducts had dilatation and the degree of dilation, whether there was a history of liver disease, whether there was a history of schistosomiasis, whether there was cancerous transformation, whether there were concurrent bile duct stones, whether there was hepatic lobe atrophy, whether there was hilar or abdominal lymph node enlargement, whether there was invasion of the bile duct wall, whether there was invasion of surrounding blood vessels, whether the tumor appears on T1-and T2 weighted imaging (T(1)WI and T(2)WI), whether the diffusion was limited, whether there was concurrent bleeding, enhancement rate, and whether there was abdominal fluid accumulation. Intraductal papillary neoplasms of the bile duct were divided into four types according to the morphological classification standards: type I (local bile duct dilation), type II (cystic), type III (free tumor), and type IV (dilated bile duct). The differences in the clinical and MRI features of the four groups of lesions were analyzed. Statistical analysis was performed with a t-test, an analysis of variance, and an χ(2)-test according to the different data. Results: Among the 90 cases with hepatic IPNB, there were 31 cases of type I, 15 cases of type II, 16 cases of type III, and 28 cases of type IV, 41 cases of liver left lobe, 11 cases of right and left lobe liver span, 7 cases of liver right lobes, 2 cases of liver caudate lobe, and 13 cases of hepatic hilar. There were statistically significant differences between the four groups (P < 0.05) in terms of age, clinical symptoms, direct bilirubin, γ-glutamyltransferase, whether they were cancerous, whether they were combined with bile duct stones, whether the liver lobes were atrophying, whether there was limited diffusion, intrahepatic bile duct diameter, and common bile duct diameter. However, there were no statistically significant differences among the four groups in gender, location, carbohydrate antigen 19-9, history of liver disease, history of schistosomiasis, carcinoembryonic antigen, alanine aminotransferase, aspartate aminotransferase, total bilirubin, whether hemorrhage was associated, lesion enhancement rate, whether the hilar/retroperitoneal lymph node was enlarged, whether the bile duct wall was invaded, whether blood vessels were invaded, and whether abdominal fluid was accumulated (P > 0.05). Conclusion: MRI manifestations have certain features for different types of intraductal papillary neoplasm of the bile duct tumors; hence, MRI aids in the diagnosis and differential diagnosis of this disease.
目的： 探讨肝内胆管内乳头状肿瘤（IPNB）的磁共振成像（MRI）特征及其分型。 方法： 回顾性分析2010年6月至2023年1月经病理证实的90例IPNB患者的资料，图像分析包括肿瘤的形态、位置、胆管有无扩张及扩张程度、有无肝病史、有无血吸虫病史、是否癌变、是否合并胆管结石、是否存在肝叶萎缩、有无肝门或腹腔淋巴结肿大、是否侵犯胆管壁、是否侵犯周围血管、肿瘤在T(1)加权成像（WI）、T(2)WI图像上的信号特征、是否扩散受限、是否合并出血、强化率、有无腹腔积液，根据形态学分类标准将IPNB分为4型，I型（局部胆管扩张型）、II型（囊肿型）、III型（无肿瘤型）、IV型(胆管扩张型)，分析4组病灶的临床及MRI特征差异。据资料不同采用t检验或方差分析、χ(2)检验进行统计学分析。 结果： 90例肝脏IPNB患者中I型31例，II型15例，III型16例，IV型28例；肝左叶41例，肝右叶11例，跨越肝左、右叶7例，肝尾状叶2例，肝门部13例；4组间在年龄、有无临床症状、直接胆红素、γ-谷氨酰转移酶、是否癌变、是否合并胆管结石、肝叶是否萎缩、是否扩散受限、肝内胆管直径、胆总管直径的比较差异有统计学意义（P<0.05）；4组间在性别、位置、糖类抗原19-9、有无肝病史、有无血吸虫病史、癌胚抗原、丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素、是否合并出血、病灶强化率、肝门/腹膜后有无肿大淋巴结、是否侵犯胆管壁、是否侵犯血管、有无腹腔积液的比较差异无统计学意义（P>0.05）。 结论： 不同类型的IPNB的MRI表现有一定的特征，MRI有助于该病的诊断与鉴别诊断。.

OBJECTIVE: Transcriptional factor prospero homeobox-1 (PROX-1) is crucial for the embryonic development of various organs and cell fate specification. It exhibits either an oncogenic or tumor suppressive activity depending on cancer types. However, the relationship between PROX-1 and hepatocellular carcinoma (HCC) remains obscure. This study was conducted to investigate the effect of PROX-1 on the invasive and oncogenic phenotypes of human HCC cells.
METHODS: The effect of PROX-1 on tumor cell behavior was investigated by using a pcDNA-myc vector and a small interfering RNA in HepG2 and Huh7 human HCC cell lines. Flow cytometry, migration, invasion, proliferation, and tube formation assays were performed. PROX-1 expression in human HCC cells was explored by western blotting.
RESULTS: PROX-1 overexpression enhanced tumor cell proliferation and inhibited apoptosis and cell cycle arrest by modulating the activities of caspase-3, PARP, and cyclin-dependent kinase inhibitors, including p21, p27, and p57 in HCC cells. After PROX-1 overexpression, the number of migrating and invading HCC cells significantly increased, and the expression levels of N-cadherin and Snail increased in HCC cells. PROX-1 overexpression enhanced angiogenesis through increased VEGF-A and VEGF-C expression and decreased angiostatin expression. PROX-1 overexpression also increased the phosphorylation of glycogen synthase kinase-3β (GSK-3β) and forkhead box O1 (FOXO1) in HCC cells. After PROX-1 knockdown, their phosphorylation was reversed.
CONCLUSIONS: PROX-1 overexpression is associated with the invasive and oncogenic phenotypes of human HCC cells via GSK-3β and FOXO1 phosphorylation.

This case study reports a rare case of a non-functioning metastatic pancreatic neuroendocrine tumor (pNET) transforming into a functioning pNET. A 59-year-old male, previously treated with distal pancreatectomy, splenectomy, lymph node dissection, liver metastasectomy, and pharmacotherapy, presented with weakness, hypoglycemia, and daily episodes of watery diarrhea. A functioning neuroendocrine liver metastasis expressing insulin and gastrin was identified. Surgical intervention, including left lateral hepatectomy and microwave ablation of multiple intrahepatic lesions, resulted in symptom resolution and uneventful recovery. However, metastatic liver disease re-emerged seven months post-surgery, necessitating chemotherapy. This case highlights the importance of vigilance for symptom development in non-functioning pNETs, signaling potential disease relapse and phenotype transformation, and suggests surgical treatment as a viable option in select cases.

OBJECTIVE: Prospective data on treatment after immune checkpoint inhibitor (ICI) therapy in hepatocellular carcinoma (HCC) are lacking. We conducted a phase II multicentre study on cabozantinib after ICI treatment in HCC.
METHODS: This is an investigator-initiated, single-arm, clinical trial involving academic centres in Hong Kong and Korea. Key eligibility criteria included diagnosis of HCC, refractoriness to prior ICI-based treatment, and Child-Pugh A liver function. A maximum of two prior lines of therapy were allowed. All patients were commenced on cabozantinib at 60 mg/day. The primary endpoint was progression-free survival (PFS).
RESULTS: Forty-seven patients were recruited from Oct 2020 to May 2022; 27 and 20 patients had received one and two prior therapies, respectively. Median follow-up was 11.2 months. The median PFS was 4.1 months (95% CI 3.3-5.3). The median overall survival (OS) was 9.9 months (95% CI 7.3-14.4), and the 1-year OS rate was 45.3%. Partial response and stable disease occurred in 3 (6.4%) and 36 (76.6%) patients, respectively. When used as a second-line treatment (n = 27), cabozantinib was associated with a median PFS and OS of 4.3 (95% CI 3.3-6.7) and 14.3 (95% CI 8.9-NR) months, respectively. The corresponding median PFS and OS were 4.3 (95% CI 3.3-11.0) and 14.3 (95% CI 9.0-NR) months, respectively, for those receiving ICI-based regimens with proven benefits (n = 17). The most common grade 3-4 treatment-related adverse event was thrombocytopenia (6.4%). The median dose of cabozantinib was 40 mg/day. The number of prior therapies was an independent prognosticator (one vs. two; hazard ratio = 0.37; p = 0.03).
CONCLUSIONS: Cabozantinib demonstrated efficacy in patients who had received prior ICI regimens; survival data for second-line cabozantinib following first-line ICI regimens provide a reference for future clinical trial design. The number of prior lines of treatment may be considered a stratification factor in randomised studies.
UNASSIGNED: Prospective data on systemic treatment following prior immune checkpoint inhibitor (ICI) therapy for hepatocellular carcinoma (HCC) are lacking. This phase II clinical trial provides efficacy and safety data on cabozantinib in patients who had received prior ICI-based treatment. Exploratory analyses showed that the performance of cabozantinib differed significantly when used as a second- or third-line treatment. The above data could be used as a reference for clinical practice and the design of future clinical trials on subsequent treatment lines following ICIs.
RESULTS:
UNASSIGNED: NCT04588051.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) reduce the risk of hepatocellular carcinoma (HCC) in patients of hepatitis B. This study compared the difference between ETV and TDF on risk of HCC recurrence and mortality in patients with HBV-related HCC after curative intent treatment.
METHODS: Patients with HBV-related HCC who received HCC treatment (surgery or radiofrequency ablation [RFA]) and underwent long-term ETV or TDF therapy were retrospectively included. Baseline characteristics including age, sex, antiviral therapy, liver reserve, HCC stages, pathology reports and treatment modality were obtained. The risk of tumor recurrence, all-cause mortality, HCC-related mortality, and liver function were compared.
RESULTS: We identified 390 HBV-related HCC patients with curative intent treatment for HCC and treated with ETV (n = 328) or TDF (n = 62) between January 2011 and December 2020. The median age was 60 years, and 90.7% patients were males. After a median follow-up of 29 months, 186 patients developed recurrent HCC and 111 died. The baseline characteristics were comparable except more ALBI grade 3 patients in TDF group (76% vs. 48%, P < 0.001). Compared to ETV group, TDF users had lower all-cause mortality (adjusted hazard ratio [aHR]: 0.38, P = 0.003), and HCC-related mortality (aHR: 0.23, P = 0.005). Lower recurrence rate was noticed in TDF users after inverse probability of treatment weighting (IPTW). TDF users had improved ALBI grade and FIB-4 index compared with ETV groups.
CONCLUSIONS: TDF therapy is associated with a reduced risk of HCC-related outcomes among patients with HBV-related HCC after curative intent treatment compared with ETV usage.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and a leading cause of cancer related death worldwide. Current guidelines for the noninvasive diagnosis of HCC are provided by the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD) which endorsed the Liver Imaging Reporting and Data System (LI-RADS) algorithm, the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC), and the Asian-Pacific Association for the Study of the Liver (APASL). These allow the diagnosis of HCC in high-risk patients in the presence of typical imaging features on contrast-enhanced CT, MRI, or contrast-enhanced ultrasound. Size, non-rim arterial phase hyperenhancement, non-peripheral washout, enhancing capsule, and growth are major imaging features and they should be combined for the diagnosis of HCC. This article provides concise and relevant practice recommendations aimed at general radiologist audience, summarizing the best practice and informing on the essential imaging criteria for the diagnosis of HCC, while also discussing the high-risk population criteria, imaging modalities, and imaging features according to the current guidelines. KEY POINTS: • Noninvasive diagnosis of hepatocellular carcinoma (HCC) can be provided only in patients at high risk. • Contrast-enhanced CT or MRI are the first-line imaging exams for the diagnosis of HCC. • Major imaging features should be combined to provide the diagnosis of definitive HCC.