OBJECTIVE: Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly ultrasounds has been shown to improve survival. However, adherence to biannual screening is currently suboptimal. This study aimed to evaluate the effect of increased HCC surveillance uptake and improved ultrasound sensitivity on mortality among people with HCV-related cirrhosis post HCV cure.
METHODS: This study utilized mathematical modelling to assess HCC progression, surveillance, diagnosis, and treatment among individuals with cirrhosis who had successfully been treated for HCV. The deterministic compartmental model incorporated Barcelona Clinic Liver Cancer (BCLC) stages to simulate disease progression and diagnosis probabilities in 100 people with cirrhosis who had successfully been treated for hepatitis C over 10 years. Four interventions were modelled to assess their potential for improving life expectancy: realistic improvements to surveillance adherence, optimistic improvements to surveillance adherence, diagnosis sensitivity enhancements, and improved treatment efficacy Results: Realistic adherence improvements resulted in 9.8 (95% CI 7.9, 11.6) life years gained per cohort of 100 over a 10-year intervention period; 17.2 (13.9, 20.3) life years were achieved in optimistic adherence improvements. Diagnosis sensitivity improvements led to a 7.0 (3.6, 13.8) year gain in life years, and treatment improvements improved life years by 9.0 (7.5, 10.3) years.
CONCLUSIONS: Regular HCC ultrasound surveillance remains crucial to reduce mortality among people with cured hepatitis C and cirrhosis. Our study highlights that even minor enhancements to adherence to ultrasound surveillance can significantly boost life expectancy across populations more effectively than strategies that increase surveillance sensitivity or treatment efficacy.

Point of care testing (POCT) of nucleic acid (NA) contributes to the timely disease diagnosis, like bacteria and virus screening in households or resource-constrained areas, but its development has always been stagnant. Herein, we proposed an exonuclease III cascaded with CRISPR/Cas12a (Exo-III/Cas12a) amplification strategy and constructed a smartphone-based portable fluorescence detector (SPFD) to repurpose the commercial alpha-fetoprotein (AFP) strip for the ultrasensitive and hand-held detection of NA samples. In detail, the target-initiated-Exo-III/Cas12a strategy realizes the signal amplification and liberates AFP from magnetic beads through the trans-cleavages of activated Cas12a toward the AFP aptamer. After magnetic separation and migration, the fluorescence signals of the test (FT) and control (FC) lines on the AFP strip were digitally output by the SPFD, and the FT/FC was employed for the quantitative analysis to minimize external disturbances and improve accuracy. We experimentally assessed the universe applicability of the proposed NA-POCT platform toward miRNA-155, 16S rRNA of Staphylococcus aureus, and ORF1a/b RNA of Covid-19 pseudovirus, achieving favorable detection limits of 42 aM, 18 CFU/mL, and 87 copies/μL, respectively. Moreover, its simplicity, universality, and admirable detection performance demonstrate a great potential in the aspect of rapidly transforming the existing POCT devices for multiple new applications at the time of need.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in China. Microvascular invasion (MVI) often indicates poor prognosis and metastasis in HCC patients. 18F-FDG PET-CT is a new imaging method commonly used to screen for tumor occurrence and evaluate tumor stage.
OBJECTIVE: This study attempted to predict the occurrence of MVI in early-stage HCC through 18F-FDG positron emission tomography (PET)/computed tomography (CT) imaging findings and laboratory data.
METHODS: A total of 113 patients who met the inclusion criteria were divided into two groups based on postoperative pathology: the MVI-positive group and MVI-negative group. We retrospectively analyzed the imaging findings and laboratory data of 113 patients. Imaging findings included tumor size, tumor maximum standard uptake value (SUVmaxT), and normal liver maximum standard uptake value (SUVmaxL). The ratios of SUVmaxT to SUVmaxL (SUVmaxT/L) and an SUVmaxT/L > 2 were defined as active tumor metabolism. The tumor size was indicated by the maximum diameter of the tumor, and a diameter greater than 5 cm was defined as a mass lesion. The laboratory data included the alpha-fetoprotein (AFP) level and the HBeAg level. An AFP concentration > 20 ng/mL was defined as a high AFP level. A HBeAg concentration > 0.03 NCU/mL was defined as HB-positive.
RESULTS: The SUVmaxT/L (p = 0.003), AFP level (p = 0.008) and tumor size (p = 0.015) were significantly different between the two groups. Patients with active tumor metabolism, mass lesions and high AFP levels tended to be MVI positive. Binary logistic regression analysis verified that active tumor metabolism (OR = 4.124, 95% CI, 1.566-10.861; p = 0.004) and high AFP levels (OR = 2.702, 95% CI, 1.214-6.021; p = 0.015) were independent risk factors for MVI. The sensitivity of the combination of these two independent risk factors predicting HCC with MVI was 56.9% (29/51), the specificity was 83.9% (52/62) and the accuracy was 71.7% (81/113).
CONCLUSIONS: Active tumor metabolism and high AFP levels can predict the occurrence of MVI in HCC patients.

BACKGROUND: Developing biosensors with antifouling properties is essential for accurately detecting low-concentration biomarkers in complex biological matrix, which is imperative for effective disease diagnosis and treatment. Herein, an antifouling electrochemical aptasensor qualifying for probing targets in human serum was explored based on newly-devised peptides that could form inverted U-shaped structures with long-term stability.
RESULTS: The inverted U-shaped peptides (U-Pep) with two terminals of thiol groups grafted onto the Au-modified electrode showcase superior antifouling properties in terms of high stability against enzymatic hydrolysis and long acting against biofouling in actual biofluids. The construction of the outlined antifouling electrochemical aptasensor just involved the fabrication of Au-deposited poly(3,4 ethylenedioxythiophene) (Au/PEDOT) modified electrode, followed by one-step co-incubation in the peptides and the aptamer probes with the Au/PEDOT electrode. Taking a typical biomarker of alpha-fetoprotein (AFP) for detection, this elegant antifouling aptasenor demonstrated a nice response for probing the target AFP with a low detection limit of 0.27 pg/mL and a wide linear scope of 1.0 pg/mL to 1.0 μg/mL, and furthermore qualified for assaying of AFP in human serum samples with satisfactory accuracy and feasibility.
CONCLUSIONS: This engineering strategy of U-Pep with long-lasting antifouling efficacy opens a new horizon for high-performance antifouling biosensors suitable for detection in complex bifluids, and it could spark more inspiration for a follow-up exploration of other featured antifouling biomaterials.

Background: Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are two tumor markers that are widely used in the differential diagnosis in patients with primary liver tumors. Very high levels of AFP are sporadically observed in patients with intrahepatic cholangiocarcinoma (ICC) and may cause an incorrect initial diagnosis of hepatocellular carcinoma (HCC). Methods: Two cases of tumors in cirrhotic livers were described, in which the initial diagnosis, based on very high AFP levels (Patient I: 10,464 ng/mL, Patient II: 2212 ng/mL, reference range: ≤8.04 ng/mL) was HCC. In addition, the PubMed database was searched for cases of ICC with elevated AFP. Discussion: In both individuals, liver cirrhosis was diagnosed, but there was no typical rapid \"washout\" in the contrast-enhanced computed tomography. Based on the histological assessment of samples obtained in the core biopsies, the initially assumed diagnosis of HCC was changed to ICC in both cases. Only nine cases of patients with ICC and high AFP levels were found in the PubMed database. The AFP levels ranged from slightly elevated to over 16,000 ng/mL. Conclusions: A very high AFP level does not necessarily correlate with the presence of HCC. Therefore, the diagnosis has to be verified histologically, when the radiological imaging is uncertain in patients with liver cirrhosis.

Alpha-foetoprotein (AFP) is taken as a diagnostic tumor marker for the screening and diagnosis of cancer. Nucleic acid-based isothermal amplification strategies are emerging as a potential technology in early screening and clinical diagnosis of AFP. The leakages between hairpins dramatically increase the background and reduce the sensitivity. Thus, it is necessary to develop some strategies to reduce the leakage for isothermal amplification strategies. A DNAzyme-locked leakless enzyme-free amplification system was developed for AFP detection in liver cancer and breast cancer. AFP could open the apt-hairpin and initiate the catalytic hairpin assembly (CHA) reaction to produce a Y-shaped duplex. Two tails of a Y-shaped duplex cleaved the two kinds of leakless hairpins. Then, the third tail of the Y-shaped duplex catalyzed the second CHA between the cleaved leakless hairpins to recover the fluorescent intensity. The limit of detection reached 5 fg/mL by the two levels of signal amplifications. Importantly, the leakless hairpin design effectively reduced leakage between hairpins and weakened the background. In addition, it also showed a great promising potential for AFP detection in early screening and clinical diagnosis.

Transjugular intrahepatic portosystemic shunt (TIPS) reduces portal hypertension complications. Its impact on hepatocellular carcinoma (HCC) remains unclear. We evaluated 42,843 liver transplant candidates with HCC from the Scientific Registry of Transplant Recipients (2002-2022). 4,484 patients with and without TIPS were propensity score-matched 1:3. Analysing wait-list changes in total tumor volume, HCC count, and alpha-fetoprotein levels, and assessing survival from listing and transplantation; TIPS correlated with a decreased nodule count (-0.24 vs. 0.04, p = 0.028) over a median wait period of 284 days (IQR 195-493) and better overall survival from listing (95.6% vs. 91.5% at 1 year, p < 0.0001). It was not associated with changes in tumor volume (0.28 vs. 0.11 cm³/month, p = 0.58) and AFP (14.37 vs. 20.67 ng/mL, p = 0.42). Post-transplant survival rates (91.8% vs. 91.7% at 1 year, p = 0.25) and HCC recurrence (5.1% vs. 5.9% at 5 years, p = 0.14) were similar, with a median follow-up of 4.98 years (IQR 2.5-8.08). While TIPS was associated with a reduced nodule count and improved waitlist survival, it did not significantly impact HCC growth or aggressiveness. These findings suggest potential benefits of TIPS in HCC management, but further studies need to confirm TIPS safety.

OBJECTIVE: To evaluate the association between serum alpha-fetoprotein (AFP) half-life (HL) and prognosis in prepubertal children with elevated AFP values 3 to 4 weeks after surgery for testicular yolk sac tumors (YST).
METHODS: Prepubertal patients with testicular YST treated with radical orchiectomy between January 2016 and December 2022 were retrospectively reviewed. Negative outcomes were defined as relapse, metastasis or death. Univariate and multivariate logistic regression analyses were conducted to select risk factors for negative outcomes.
RESULTS: A total of 42 patients were eventually enrolled into the study. Patients were divided into non-negative and negative outcomes groups, consisting of 35 and 7 patients, respectively. Thirty-five patients were stage I, two cases were stage II, and five cases were stage IV, according to the Children\'s Oncology Group staging system. The overall survival (OS) rate was 100%. Average AFP values significantly decreased after resection (P < 0.001). A significant positive correlation was shown between pre- and postoperative AFP values (r = 0.60, P < 0.001). Long AFP HL was considered as an independent risk factor for negative outcomes in YST patients underwent radical orchiectomy (P = 0.04). The cut-off value for AFP HL was 5.78 days, regardless of age division.
CONCLUSIONS: Testicular YST is a relatively rare disease in children with an OS of 100%, and salvage chemotherapy is effective even in grade IV patients. The postoperative AFP HL was significantly associated with prognosis in prepubertal patients with testicular YST. The cut-off value for AFP HL is 5.78 days regardless of the effect of physiological AFP elevation.

Objective: To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED). Methods: The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis. Results: Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177-GNAS, AIM1-FGFR3, and EPHA6-ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis (P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone (P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone (P＜0.05). Conclusions: Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.
目的： 探讨血清甲胎蛋白（AFP）升高伴肠母细胞分化胃腺癌（GAED）患者的免疫表型和分子生物学特征。 方法： 收集2018—2020年山西省肿瘤医院收治的13例血清AFP升高且伴有GAED患者的临床病理资料，应用免疫组织化学（IHC）及二代测序方法对13例血清AFP升高伴GAED患者的病理组织进行免疫标志物和分子生物学特征分析，生存分析采用Kaplan-Meier法和Log rank检验。 结果： 13例GAED患者中，男12例，女1例，年龄41～70岁，中位年龄64岁，病灶位置以胃窦部（5例）、胃体部（4例）为主。IHC显示可表达瘤胚胎蛋白（AFP、SALL4、GPC3）、肠上皮分化蛋白（CDX-2、CD10）和一些原始肠上皮表型标志物（OCT3/4、Claudin6），联合应用多种标志物诊断可降低漏诊率。13例患者中，12例存在至少1个基因突变（1个基因突变：1例，2～5个基因突变：3例，6～15个基因突变：8例），1例未检测到突变。突变频率最高的基因是TP53（10例），其他突变基因包括EPHB1（3例）、ATRX（2例）、EPHA5（2例）、GATA3（2例）、LRP1B（2例）和MAP2K4（2例）。13例患者中3例存在基因结构变异，分别为C14orf177-GNAS、AIM1-FGFR3、EPHA6-ROS1基因重排。13例患者均存在拷贝数变异，11例患者存在2个以上基因的拷贝数变异。常见的扩增基因为IRS2（5例）、PTEN（5例）、GNAS（4例）、CCNE1（3例）、CEBPA（3例）、PCK1（3例）、ERBB2（2例），常见的缺失基因为SOX2（5例）、MYC（5例）。13例患者中，死亡4例，死亡患者中有2例出现肝转移；无病生存患者4例，5例患者病情进展，其中3例出现腹腔转移，2例出现肝转移。血清AFP升高伴GAED患者3年生存率为65.9%，3年无进展生存率为30.7%。基因LRP1B点突变与预后不良有关（P＜0.001）。行免疫治疗较单纯化疗的患者预后无明显改善（P=0.595），但进行术后化疗或术后化疗加免疫治疗较只进行手术患者预后好（均P＜0.05）。 结论： 血清AFP升高伴GAED是一种具有高度侵袭性的肿瘤，有独特的分子特征，往往同时伴有多个分子事件，TP53突变是其最常见的基因突变类型，此外，部分患者伴有人表皮生长因子受体2扩增和基因重排。.

BACKGROUND: Several studies have indicated that BALAD score which includes the HCC tumor markers of HCC, AFP, AFP-L3%, DCP, and serum albumin and bilirubin value were good predictors of HCC patients for all treatment modalities. In this study, we aim to clarify the impact of BALAD score as the prognostic factor for HCC patients after curative surgery.
METHODS: This study investigated 578 patients who underwent hepatectomy for HCC between January 2003 and May 2013. Cumulative recurrence rate, overall survival (OS), and clinicopathological parameters were analyzed according to the level of BALAD score.
RESULTS: In patients with higher BALAD score, recurrence rate and OS was poor (p = 0.0015 and p < 0.0001, respectively). Multivariate analyses revealed independent risk factors for recurrence to be male (hazard ratio [HR] 1.52, P = 0.011), HCV-antibody positive (HR 1.33, P = 0.019), multiple tumors (HR 2.16, P < 0.0001), microvascular invasion (HR 1.45, P = 0.0035) and higher BALAD score (RR 1.70, P = 0.015). The independent risk factors for OS were multiple tumors (HR 1.52, P = 0.014), microvascular invasion (HR 1.53, P = 0.012), and higher BALAD score (RR 2.51, P = 0.0012).
CONCLUSIONS: BALAD score is associated with high recurrence rate and poor overall survival of the patients who underwent curative liver resection for HCC.