Presence Of Microvascular Invasion Research Articles

Cross-institutional evaluation of deep learning and radiomics models in predicting microvascular invasion in hepatocellular carcinoma: validity, robustness, and ultrasound modality efficacy comparison

PurposeTo conduct a head-to-head comparison between deep learning (DL) and radiomics models across institutions for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) and to investigate the model robustness and generalizability through rigorous internal and external validation.MethodsThis retrospective study included 2304 preoperative images of 576 HCC lesions from two centers, with MVI status determined by postoperative histopathology. We developed DL and radiomics models for predicting the presence of MVI using B-mode ultrasound, contrast-enhanced ultrasound (CEUS) at the arterial, portal, and delayed phases, and a combined modality (B + CEUS). For radiomics, we constructed models with enlarged vs. original regions of interest (ROIs). A cross-validation approach was performed by training models on one center’s dataset and validating the other, and vice versa. This allowed assessment of the validity of different ultrasound modalities and the cross-center robustness of the models. The optimal model combined with alpha-fetoprotein (AFP) was also validated. The head-to-head comparison was based on the area under the receiver operating characteristic curve (AUC).ResultsThirteen DL models and 25 radiomics models using different ultrasound modalities were constructed and compared. B + CEUS was the optimal modality for both DL and radiomics models. The DL model achieved AUCs of 0.802–0.818 internally and 0.667–0.688 externally across the two centers, whereas radiomics achieved AUCs of 0.749–0.869 internally and 0.646–0.697 externally. The radiomics models showed overall improvement with enlarged ROIs (P < 0.05 for both CEUS and B + CEUS modalities). The DL models showed good cross-institutional robustness (P > 0.05 for all modalities, 1.6–2.1% differences in AUC for the optimal modality), whereas the radiomics models had relatively limited robustness across the two centers (12% drop-off in AUC for the optimal modality). Adding AFP improved the DL models (P < 0.05 externally) and well maintained the robustness, but did not benefit the radiomics model (P > 0.05).ConclusionCross-institutional validation indicated that DL demonstrated better robustness than radiomics for preoperative MVI prediction in patients with HCC, representing a promising solution to non-standardized ultrasound examination procedures.

Growth differentiation factor 7 alleviates the proliferation and metastasis of hepatocellular carcinoma

Background and aimInflammatory factors play significant roles in the development and occurrence of hepatocellular carcinoma (HCC). However, the tumor-protective functions of growth differentiation factors (GDFs) in HCC are yet to be clarified. In this study, we aimed to evaluate the expression levels of 10 GDFs in tumor and paratumor tissues from patients with HCC and perform in vitro and in vivo experiments to elucidate the role of GDF7 in regulating the proliferation and metastasis of HCC. MethodsThe gene expression of 10 GDFs was compared between HCC and paratumors using The Cancer Genome Atlas dataset and patient-derived tissues. A tumor microarray containing 108 HCC tissue samples was used to explore the prognostic value of GDF7 expression. Loss-of-function experiments were also performed in vitro and in vivo to investigate the role of GDF7 in HCC. ResultsThe mRNA and protein levels of GDF7 were significantly lower in HCC tumors than in paratumors (P < 0.001). Kaplan–Meier analysis showed that decreased GDF7 expression in HCC was associated with worse overall survival (5-year rate: 61.8% vs. 27.5%, P < 0.001) and increased recurrence risk (P < 0.001). Multivariate Cox regression analysis demonstrated that low GDF7 expression, the presence of microvascular invasion, and elevated alpha-fetoprotein (AFP) levels were independent risk factors for tumor recurrence and poor survival. Downregulation of GDF7 also increased the tumor growth in HCC cells and in an HCC xenograft model. GDF7 knockdown promoted migration and invasion via epithelial–mesenchymal transition. Meanwhile, a negative correlation between JunB proto-oncogene (JUNB) and GDF7 was observed in HCC tissues. Modulating JUNB levels altered GDF7 protein expression. ConclusionGDF7 is a potential biomarker for predicting superior outcomes in patients with HCC. GDF7 amplification is a potential therapeutic option for HCC.

Adjuvant therapy with donafenib plus anti–PD-1 antibody for patients (pts) with hepatocellular carcinoma (HCC) at high risk of recurrence after resection (PATH study).

e16228 Background: There is no universally accepted standard treatment option or strategy for post-surgery adjuvant therapy for HCC. Among BCLC A/B patients with MVI, adjuvant TACE provided a 1-year recurrence-free survival rate (RFSR) of around 60-70%. We conducted a pilot study to explore the utility of donafenib combined with anti-PD-1 antibody as adjuvant therapy for pts with high risks of recurrence. Methods: It was planned to enroll 30 HCC pts who had undergone radical surgery and with at least one of the following risk factors: a) Presence of microvascular invasion (MVI); b) Presence of satellite nodule(s); c) &gt; 3 tumor nodules; d) Portal vein tumor thrombus. Pts with invasion of main portal venous were excluded. Donafenib plus anti-PD-1 antibody was initiated at 4 to 8 weeks after resection and continued for up to six months. No other adjuvant therapies were allowed before enrollment and during the study, except for anti-virus treatment. The primary endpoint was the cumulative 1-year RFSR. The secondary endpoints included recurrence-free survival (RFS), overall survival, and safety. Results: From June 2020 to November 2023, a total of 30 pts were recruited. 27 pts were included in efficacy analysis. The mean and median follow-up time was 347.9 days and 179.5 days. The mean and median time from surgery to enrollment was 42.5 days and 42.0 days. MVI was the most common risk factor (Table). Majority of the pts had only one risk factor. Relapse occurred in two pts (7.4%) and RFS was very immature. The RFSR at one year was 89.7% (90% CI, 70.6%-96.7%) in all the evaluable pts, and slightly higher in pts with M1 or only one risk factor (92.9% [90% CI, 68.1%-98.6%] and 93.3% [90% CI, 69.9%-98.7%], respectively). No deaths were observed. In 30 pts who had received at least one dose, the incidence of grade 3 treatment-related adverse events (TRAEs) was 40.0% (12/30). No grade 4 or 5 TRAEs were reported. The grade 3 TRAEs occurred in ≥2 pts were palmar-plantar erythrodysesthesia syndrome (13.3%), rash (13.3%), alanine aminotransferase increased (10.0%), and aspartate aminotransferase increased (6.7%). Conclusions: These results showed that a regimen of 6 months of adjuvant therapy with donafenib plus anti-PD-1 antibody may be efficient to reduce recurrence for BCLC A/B pts at high risk of recurrence, particularly those with ≤2 risk factors. No new safety issues were noticed. Clinical trial information: NCT04418401 . [Table: see text]

Nomogram for preoperative estimation of microvascular invasion risk in hepatocellular carcinoma

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167–7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922–41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374–12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780–10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771–0.894) and 0.821 (95 % CI 0.720–0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

Microvascular invasion is associated with poor prognosis in renal cell carcinoma: a retrospective cohort study and meta-analysis.

This retrospective cohort study and meta-analysis aims to explore the association between microvascular invasion (MVI) and clinicopathologiccal features, as well as survival outcomes of patients with renal cell carcinoma (RCC). The retrospective cohort study included 30 RCC patients with positive MVI and another 75 patients with negative MVI as controls. Clinicopathological features and follow-up data were compiled. The meta-analysis conducted searches on PubMed, Cochrane Library, Web of Science, Embase, and WanFang Data from the beginning to 30 September 2023, for comparative studies relevant to MVI patients. The Newcastle-Ottawa Scale and Egger Test were used to assess the risk of biases and certainty of evidence in the included studies. The cohort study showed that MVI was associated with advanced primary tumor stage, high pathological grades, high tumor size, high clinical symptoms and lymph node invasion (P <0.05). Kaplan-Meier analyses demonstrated MVI was associated with worse CSS rates when compared to MVI negative group (P <0.05). However, in the multivariate analysis it was not presented as an independent predictor of cancer survival mortality (P >0.05). The meta-analysis part included 11 cohort studies. The results confirmed that patients with MVI positive had worse 12 and 60 mo CSS rates (HR12mo = 0.86, 95%CI 0.80-0.92; HR60mo = 0.63, 95% CI 0.55-0.72; P < 0.00001). Moreover, the meta-analysis also confirmed that MVI group was associated with higher rate of advanced tumor stage, pathological grades, tumor size diameter, higher rate of clinical symptoms and lymph node invasion (P <0.05). The presence of MVI in renal cell carcinoma patients is linked to poorer survival outcomes and worse clinicopathological features. In spite of this, it does not seem to be an independent predictor for cancer survival mortality in renal cell carcinoma. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023470640, identifier CRD42023470640.

Survival effects of postoperative adjuvant TACE in early-HCC patients with microvascular invasion: A multicenter propensity score matching.

Background: The presence of microvascular invasion (MVI) significantly worsens the surgical outcome of hepatocellular carcinoma (HCC). The purpose of this research was to investigate the survival benefit of adjuvant transarterial chemoembolization (TACE) in patients with MVI after hepatectomy. Methods: A retrospective analysis was conducted on 1372 HCC patients who underwent curative liver resection in four medical institutions. In order to minimize confounding factors and selection bias between groups, Propensity Score Matching (PSM) (1:1) was performed to ensure balanced clinical characteristics. Results: A total of 1056 patients were enrolled after PSM, including 672 patients with MVI and 384 patients without MVI. Adjuvant TACE improves DFS (Median, 36 months vs 14 months, p < 0.001) and OS (Median, NA vs 32 months, p < 0.001) in patients harboring MVI, but not in those (all p > 0.05) lacking MVI. In different different CNLC stages, adjuvant TACE improved DFS (CNLC stage I, Median, 37 vs 15 months; CNLC stage II, Median, 25 vs 11 months, p < 0.001) and OS (CNLC stage I, Median, NA vs 32 months, p < 0.001; CNLC stage II, Median, NA vs 26 months, p = 0.002) in patients who carried MVI, but not in those (CNLC stage I-II, all p > 0.05) who lacked MVI. Conclusions: Adjuvant TACE may be a potentially effective treatment option for improving survival outcomes in early-HCC patients harboring MVI, but not in those lacking MVI.

Prognostic potential of preoperative circulating tumor cells to predict the early progression recurrence in hepatocellular carcinoma patients after hepatectomy

BackgroundThe role of circulating tumor cells (CTCs) in prognosis prediction has been actively studied in hepatocellular carcinoma (HCC) patients. However, their efficiency in accurately predicting early progression recurrence (EPR) is unclear. This study aimed to investigate the clinical potential of preoperative CTCs to predict EPR in HCC patients after hepatectomy.MethodsOne hundred forty-five HCC patients, whose preoperative CTCs were detected, were enrolled. Based on the recurrence times and types, the patients were divided into four groups, including early oligo-recurrence (EOR), EPR, late oligo-recurrence (LOR), and late progression recurrence (LPR).ResultsAmong the 145 patients, 133 (91.7%) patients had a postoperative recurrence, including 51 EOR, 42 EPR, 39 LOR, and 1 LPR patient. Kaplan–Meier survival curve analysis indicated that the HCC patients with EPR had the worst OS. There were significant differences in the total-CTCs (T-CTCs) and CTCs subtypes count between the EPR group with EOR and LOR groups. Cox regression analysis indicated that the T-CTC count of > 5/5 mL, the presence of microvascular invasion (MVI) and satellite nodules were the independent risk factors for EPR. The efficiency of T-CTCs was superior as compared to those of the other indicators in predicting EPR. Moreover, the combined model demonstrated a markedly superior area under the curve (AUC).ConclusionsThe HCC patients with EPR had the worst OS. The preoperative CTCs was served as a prognostic indicator of EPR for HCC patients. The combined models, including T-CTCs, MVI, and satellite nodules, had the best performance to predict EPR after hepatectomy.

MRI-based radiomics signature: a potential imaging biomarker for prediction of microvascular invasion in combined hepatocellular-cholangiocarcinoma.

To investigate the potential of radiomics analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in preoperatively predicting microvascular invasion (MVI) in patients with combined hepatocellular-cholangiocarcinoma (cHCC-CC) before surgery. A cohort of 91 patients with histologically confirmed cHCC-CC who underwent preoperative liver DCE-MRI were enrolled and divided into a training cohort (27 MVI-positive and 37 MVI-negative) and a validation cohort (11 MVI-positive and 16 MVI-negative). Clinical characteristics and MR features of the patients were evaluated. Radiomics features were extracted from DCE-MRI, and a radiomics signature was built using the least absolute shrinkage and selection operator (LASSO) algorithm in the training cohort. Prediction performance of the developed radiomics signature was evaluated by utilizing the receiver operating characteristic (ROC) analysis. Larger tumor size and higher Radscore were associated with the presence of MVI in the training cohort (p = 0.026 and < 0.001, respectively), and theses findings were also confirmed in the validation cohort (p = 0.040 and 0.001, respectively). The developed radiomics signature, composed of 4 stable radiomics features, showed high prediction performance in both the training cohort (AUC = 0.866, 95% CI 0.757-0.938, p < 0.001) and validation cohort (AUC = 0.841, 95% CI 0.650-0.952, p < 0.001). The radiomics signature developed from DCE-MRI can be a reliable imaging biomarker to preoperatively predict MVI in cHCC-CC.

Dynamic contrast-enhanced ultrasonography with sonazoid predicts microvascular invasion in early-stage hepatocellular carcinoma.

Microvascular invasion (MVI) is an independent risk factor for the early recurrence and poor survival of hepatocellular carcinoma (HCC). This study aims to investigate the potential clinical value of dynamic contrast-enhanced ultrasound (DCE-ultrasound)-Sonazoid in pre-operatively assessing MVI in HCC. This single centre prospective study included 140 patients with histopathologically confirmed single HCC lesions. Patients were classified according to the post-operative pathological information presence of MVI: MVI+ group (n = 32) and MVI- group (n = 108). All patients underwent DCE-ultrasound within 1 week before surgery. The quantitative perfusion parameters of HCC lesions, margins of HCC lesions, and distal liver parenchyma were obtained and analyzed. Clinicopathological (serum alpha-fetoprotein, Des-gamma-carboxyprothrombin, and pathological grade) and grayscale imaging features (tumor size) were significantly different between the MVI+ and MVI- groups (p < 0.05). Further quantitative analysis showed that when comparing the MVI+ and MVI- groups, half-decrease time and wash-out rate of HCC lesions and peak enhancement in the arterial phase of difference between the margin area of HCC and distal liver parenchyma were significantly different (p = 0.045, p = 0.035, and p = 0.023, respectively). Combining the above three quantitative parameters, the accuracy, sensitivity, specificity, positive-predictive value, and negative-predictive value were 69.3% (97/140), 37.8% (17/45), 84.3% (80/95), 53.1% (17/32), 74.1% (80/108), respectively. DCE-ultrasound with quantitative perfusion analysis has the potential to predict MVI in HCC lesions. DCE-ultrasound with quantitative perfusion analysis has the potential to predict MVI in HCC lesions.

Modality-based attention and dual-stream multiple instance convolutional neural network for predicting microvascular invasion of hepatocellular carcinoma.

The presence of microvascular invasion (MVI) is a crucial indicator of postoperative recurrence in patients with hepatocellular carcinoma (HCC). Detecting MVI before surgery can improve personalized surgical planning and enhance patient survival. However, existing automatic diagnosis methods for MVI have certain limitations. Some methods only analyze information from a single slice and overlook the context of the entire lesion, while others require high computational resources to process the entire tumor with a three-dimension (3D) convolutional neural network (CNN), which could be challenging to train. To address these limitations, this paper proposes a modality-based attention and dual-stream multiple instance learning(MIL) CNN. In this retrospective study, 283 patients with histologically confirmed HCC who underwent surgical resection between April 2017 and September 2019 were included. Five magnetic resonance (MR) modalities including T2-weighted, arterial phase, venous phase, delay phase and apparent diffusion coefficient images were used in image acquisition of each patient. Firstly, Each two-dimension (2D) slice of HCC magnetic resonance image (MRI) was converted into an instance embedding. Secondly, modality attention module was designed to emulates the decision-making process of doctors and helped the model to focus on the important MRI sequences. Thirdly, instance embeddings of 3D scans were aggregated into a bag embedding by a dual-stream MIL aggregator, in which the critical slices were given greater consideration. The dataset was split into a training set and a testing set in a 4:1 ratio, and model performance was evaluated using five-fold cross-validation. Using the proposed method, the prediction of MVI achieved an accuracy of 76.43% and an AUC of 74.22%, significantly surpassing the performance of the baseline methods. Our modality-based attention and dual-stream MIL CNN can achieve outstanding results for MVI prediction.

Neoadjuvant Intensity Modulated Radiotherapy for a Single and Small (

The presence of microvascular invasion (MVI) significantly impairs postoperative long-term survival of patients with hepatocellular carcinoma (HCC). The role of neoadjuvant radiotherapy (RT) in treating patients with an early-stage HCC predicted to have high risks of MVI remains to be explored. Consecutive patients with a resectable single and small (<= 5cm) Hepatitis B Virus (HBV)-related HCC predicted to have high risks of MVI were randomized 1:1 to receive either neoadjuvant intensity modulated radiation therapy (18Gy with fractionated doses of 3Gy) followed by surgery 4 weeks later or upfront surgery. The primary endpoint was disease-free survival (DFS). The secondary outcomes included overall survival (OS), objective response rate, RT-related toxicity and surgical complications. There were 30 patients randomized to each of the 2 groups. In the neoadjuvant RT group, 3 patients violated the study protocol, with 2 having upfront hepatectomy and 1 radiofrequency ablation after RT. The objective response rate after RT was 25.0% (7/28), but 2 patients suffered from grade 3 liver toxicity. The median follow-up was 68 months (interquartile range, 58-70mo) in the neoadjuvant RT group, and 68 months (interquartile range, 62-75mo) in the upfront surgery group. On intention-to-treat analysis, the median DFS and median OS were not reached in both the 2 arms. The 1-, 2-, 3- and 5-year DFS rates for the neoadjuvant RT group were 86.7%, 76.7%, 60.0% and 56.3%, versus 90.0%, 66.7%, 52.8% and 45.7% in the upfront surgery group (P = 0.448), respectively. The corresponding OS rates were 96.7%, 86.7%, 83.3% and 72.7%, versus 100.0%, 93.3%, 79.6% and 60.7% (P = 0.399). For patients with a resectable single and small HBV-related HCC predicted to have high risks of MVI, neoadjuvant RT gave a promising response rate with a mild toxicity. Nevertheless, the neoadjuvant RT yielded similar long-term DFS and OS rates compared to patients who underwent upfront surgery.

A novel predictive model of microvascular invasion in hepatocellular carcinoma based on differential protein expression

BackgroundThis study aims to construct and verify a nomogram model for microvascular invasion (MVI) based on hepatocellular carcinoma (HCC) tumor characteristics and differential protein expressions, and explore the clinical application value of the prediction model.MethodsThe clinicopathological data of 200 HCC patients were collected and randomly divided into training set and validation set according to the ratio of 7:3. The correlation between MVI occurrence and primary disease, age, gender, tumor size, tumor stage, and immunohistochemical characteristics of 13 proteins, including GPC3, CK19 and vimentin, were statistically analyzed. Univariate and multivariate analyzes identified risk factors and independent risk factors, respectively. A nomogram model that can be used to predict the presence of MVI was subsequently constructed. Then, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were conducted to assess the performance of the model.ResultsMultivariate logistic regression analysis indicated that tumor size, GPC3, P53, RRM1, BRCA1, and ARG were independent risk factors for MVI. A nomogram was constructed based on the above six predictors. ROC curve, calibration, and DCA analysis demonstrated the good performance and the clinical application potential of the nomogram model.ConclusionsThe predictive model constructed based on the clinical characteristics of HCC tumors and differential protein expression patterns could be helpful to improve the accuracy of MVI diagnosis in HCC patients.

Research progress of radiomics in the evaluation of microvascular invasion in hepatocellular carcinoma

Microvascular invasion (MVI) is an independent predictor of early recurrence and poor prognosis following hepatocellular carcinoma (HCC) resection and transplantation. As a novel non-invasive diagnostic tool, radiomics can extract the quantitative imaging features of tumors and peritumoral tissues with high throughput, providing more information on tumor heterogeneity than conventional and functional imaging of visual analysis and having a good application prospect in predicting the presence of MVI in HCC patients, thereby improving the accuracy of HCC diagnosis and prognosis. The value of the multimodal radiomics method based on various imaging methods in evaluating the possibility of MVI in HCC patients is elucidated here in combination with the latest research progress.

A nomogram for preoperative prediction of microvascular invasion in ruptured hepatocellular carcinoma.

Microvascular invasion (MVI) is defined as the presence of micrometastatic cancer cell emboli in hepatic vessels, including small vessels, and at present, researchers believe that is an important factor for early postoperative recurrence and survival. Here, we developed and validated a preoperative predictive model for the presence of MVI in patients with ruptured hepatocellular carcinoma (rHCC). We retrospectively collected data for 210 rHCC patients who underwent staged hepatectomy at Wuhan Tongji Hospital, and 91 patients who underwent staged hepatectomy at Zhongshan People's Hospital between January 2010 and March 2021. Then, the former was used as the training cohort and the latter was used as the validation cohort. Logistic regression was used to screen for variables associated with MVI, and these variables were used to construct nomograms. We used R software to assess the discrimination, calibration ability, as well as clinical efficacy of nomograms. Multivariate logistic regression analysis identified four risk factors independently associated with MVI: max tumor length [odds ratio (OR) = 1.385; 95% confidence interval (CI), 1.072-1.790], number of tumors (OR = 2.182; 95% CI, 1.129-5.546), direct bilirubin (OR = 1.515; 95% CI, 1.189-1.930), and alpha-fetoprotein (cutoff = 400 ng/mL) (OR = 2.689; 95% CI, 3.395-13.547). Nomograms were built from the four variables and they were tested for discrimination and calibration, and the results were good. We developed and validated a preoperative predictive model for the presence of MVI in patients with ruptured HCC. This model can help clinicians identify patients at risk of MVI and make better treatment options.

Predictive factors of microvascular invasion in patients with intrahepatic mass-forming cholangiocarcinoma based on magnetic resonance images.

The aim of this retrospective study was to develop and validate a preoperative nomogram for predicting microvascular invasion (MVI) in patients with intrahepatic mass-forming cholangiocarcinoma (IMCC) based on magnetic resonance imaging (MRI). In this retrospective study, 224 consecutive patients with clinicopathologically confirmed IMCC were enrolled. Patients whose data were collected from February 2010 to December 2020 were randomly divided into the training (131 patients) and internal validation (51 patients) datasets. The data from January 2021 to November 2021 (42 patients) were allocated to the time-independent validation dataset. Univariate and multivariate forward logistic regression analyses were used to identify preoperative MRI features that were significantly related to MVI, which were then used to develop the nomogram. We used the area under the receiver operating characteristic curve (AUC) and calibration curve to evaluate the performance of the nomogram. Interobserver agreement of MRI qualitative features was good to excellent, with κ values of 0.613-0.882. Multivariate analyses indicated that the following variables were independent predictors of MVI: multiple tumours (odds ratio [OR]) = 4.819, 95% confidence interval [CI] 1.562-14.864, P = 0.006), ill-defined margin (OR = 6.922, 95% CI 2.883-16.633, P < 0.001), and carbohydrate antigen 19-9 (CA 19-9) > 37U/ml (OR = 2.890, 95% CI 1.211-6.897, P = 0.017). A nomogram incorporating these factors was established using well-fitted calibration curves. The nomogram showed good diagnostic efficacy for MVI, with AUC values of 0.838, 0.819, and 0.874 for the training, internal validation, and time-independent validation datasets, respectively. A nomogram constructed using independent factors, namely the presence of multiple tumours, ill-defined margins, and CA 19-9 > 37U/ml could predict the presence of MVI. This can facilitate personalised therapeutic strategy and clinical management in patients with IMCC.

A diagnostic test of three-dimensional magnetic resonance elastography imaging for preoperative prediction of microvascular invasion in patients with T1 stage clear cell renal carcinoma.

Detection of microvascular invasion (MVI) of kidney tumors is important for selecting the optimal therapeutic strategy. Currently, the prediction of MVI lacks an accurate imaging biomarker. This study evaluated the performance of three-dimensional (3D) magnetic resonance elastography (MRE) imaging in predicting microvascular invasion (MVI) of T1 stage clear cell renal carcinoma (ccRCC). In this prospective study, we conducted pre-surgical imaging with a clinical 3.0 T magnetic resonance imaging (MRI) system. Firstly, 83 consecutive patients were enrolled in this study. A 3D MRE stiffness map was generated and transferred to a post-processing workstation. Contrast-enhanced computed tomography (CT) was conducted to calculate the tumor enhancement ratio. The presence of MVI was evaluated by histopathological analysis and graded according to the risk stratification based upon the number and distribution. The mean stiffness and CT tumor enhancement ratio was calculated for tumors with or without MVI. The diagnostic performance [sensitivity, specificity, positive predictive value, negative predictive value, area under the curve (AUC)] and independent predicting factors for MVI were investigated. Finally, A total of 80 patients (aged 46.7±13.2 years) were enrolled, including 22 cases of tumors with MVI. The mean MRE stiffness of kidney parenchyma and kidney tumors was 4.8±0.2 and 4.5±0.7 kPa, respectively. There was significant difference in the mean MRE stiffness between tumors with MVI (5.4±0.6 kPa) and tumors without MVI (4.1±0.3 kPa) (P<0.05). The sensitivity, specificity, positive predictive value, negative predictive value, and the AUC for mean stiffness in the prediction of MVI were 100%, 75%, 63%, 96%, and 0.87 [95% confidence interval (CI): 0.72, 0.94], respectively. The corresponding values for the CT tumor enhancement ratio were 90%, 80%, 63%, 96%, and 0.88 (95% CI: 0.71, 0.93), respectively. The odds ratio (OR) value for MRE tumor stiffness and CT kidney tumor enhancement ratio in the prediction of MVI was 2.9 (95% CI: 1.8, 3.7) and 1.2 (95% CI: 1.0, 1.7), respectively (P>0.05). 3D MRE imaging has promising diagnostic performance for predicting MVI in T1 stage ccRCC, which may improve the reliability of surgical strategy selection with T1 stage ccRCC.

Microscopic vascular invasion may not be associated with survival of patients undergoing resection for solitary hepatoma of ≤ 2 cm.

To determine the impact of microvascular invasion (MVI) on outcome in patients with solitary hepatocellular carcinoma (HCC) of ≤ 2 cm undergoing liver resection (LR). This retrospective study enrolled consecutive patients between 2007-2019 with newly diagnosed solitary HCC ≤ 2 cm who were undergoing LR at our institution. Overall survival (OS) and recurrent-free survival (RFS) were compared between patients with or without MVI. Of the 229 patients included in this study, 71 had MVI. The median follow-up period was 28.8 months (interquartile range: 13.5-70.1). Although the 90-day mortality rate was 0, 18 deaths occurred during the study, and the 5-year survival rate was 87.1%. Tumor recurrence occurred in 45 cases, and 5-year RFS was 71.9%. The presence or absence of MVI did not significantly affect the OS and RFS rates (log rank test, p = 0.10 and 0.38, respectively). In univariate and multivariate analysis, the presence of MVI was not associated with OS and RFS. The presence of MVI was not associated with OS and RFS in patients with solitary HCC ≤ 2 cm who underwent LR in this cohort.

High Platelet Count is a Potential Prognostic Factor of the Early Recurrence of Hepatocellular Carcinoma in the Presence of Circulating Tumor Cells.

Recent studies indicated the vital role of platelet in enhancing the survival of circulating tumor cells (CTCs) in the blood, thereby stimulating the metastasis of tumors. CTCs have been considered an indicator of early tumor recurrence. Therefore, this study evaluated the prognostic potential of platelet count in predicting the early recurrence of hepatocellular carcinoma (HCC) in the presence of CTCs. 127 patients, whose preoperative CTCs were detected, were enrolled in this study. Univariate analysis was performed to identify the significant association of factors with the early recurrence of HCC, followed by multivariate analysis to determine the independent prognostic indicators. The prediction potential was evaluated using receiver operating characteristic (ROC) curves. A total of 81 (63.7%) patients showed early HCC recurrence. The platelet count ≥225×109/L (hazard ratio, HR: 1.679, P = 0.041), CTCs >5/5 mL (HR: 2.467, P = 0.001), and presence of microvascular invasion (MVI) (HR: 2.580, P = 0.002) were independent factors correlated with the early recurrence of HCC in multivariate analysis. The prognostic potential of the combined CTCs-platelet count (0.738) was better than that of CTCs (0.703) and platelet (0.604) alone. The subgroup analysis, excluding 23 patients with pathological cirrhosis and splenomegaly, showed that the platelet count ≥225×109/L and CTCs >5/5 mL were also independent factors of early HCC recurrence. The prediction potential of the combined CTCs-platelet count was 0.753, which was better than that of the whole cohort. Kaplan-Meier survival curve analysis indicated that the HCC patients with high platelet or CTCs had the worse recurrence-free survival (RFS). The high platelet count was an independent factor of early HCC recurrence in the presence of CTCs. The combination of preoperative CTCs and platelet count could effectively predict the early recurrence of HCC. The subgroup analysis also showed similar results.

Preoperative tumor abnormal protein is a promising biomarker for predicting hepatocellular carcinoma oncological outcome following curative resection.

The objective of this study was to explore the potential relationship between tumor abnormal protein (TAP) and the prognosis of hepatocellular carcinoma (HCC) after a radical hepatectomy. This retrospective study included 168 HCC patients (tumor recurrence in 78 patients) who underwent a curative resection from January 2018 to June 2020. The whole population was categorized into a TAP high (≥224.6 μm2) or a TAP low group (<224.6 μm2). There was no correlation between maximum tumor size and TAP. In the whole population or subgroups stratified by maximum tumor size, the recurrence-free survival (RFS) rate of the TAP low group was significantly higher than TAP high group (P < 0.05 for all). The multivariate analysis revealed that TAP (hazard ratio [HR], 3.47; 95% confidence interval [CI], 2.18-5.51; P < 0.001), large tumor size (HR, 2.18; 95% CI, 1.36-3.49; P < 0.001), poor tumor differentiation (HR, 0.53; 95% CI, 0.33-0.84; P = 0.007), and presence of microvascular invasion (MVI) (HR, 2.03; 95% CI, 1.28-3.22; P = 0.003) were independently associated with RFS. The prognostic implication of the nomogram incorporating TAP, maximum tumor diameter, tumor differentiation, and MVI was stronger than the model without TAP. The present study suggests that higher preoperative TAP is correlated with undesirable prognosis in HCC patients who underwent a radical hepatectomy. Our study provides a robust nomogram for RFS of postoperative HCC patients.

Efficacy of texture analysis of pre-operative magnetic resonance imaging in predicting microvascular invasion in hepatocellular carcinoma.

Presence of microvascular invasion (MVI) indicates poorer prognosis post-curative resection of hepatocellular carcinoma (HCC), with an increased chance of tumour recurrence. By present standards, MVI can only be diagnosed post-operatively on histopathology. Texture analysis potentially allows identification of patients who are considered 'high risk' through analysis of pre-operative magnetic resonance imaging (MRI) studies. This will allow for better patient selection, improved individualised therapy (such as extended surgical margins or adjuvant therapy) and pre-operative prognostication. This study aims to evaluate the accuracy of texture analysis on pre-operative MRI in predicting MVI in HCC. Retrospective review of patients with new cases of HCC who underwent hepatectomy between 2007 and 2015 was performed. Exclusion criteria: No pre-operative MRI, significant movement artefacts, loss-to-follow-up, ruptured HCCs, previous hepatectomy and adjuvant therapy. Fifty patients were divided into MVI (n = 15) and non-MVI (n = 35) groups based on tumour histology. Selected images of the tumour on post-contrast-enhanced T1-weighted MRI were analysed. Both qualitative (performed by radiologists) and quantitative data (performed by software) were obtained. Radiomics texture parameters were extracted based on the largest cross-sectional area of each tumor and analysed using MaZda software. Five separate methods were performed. Methods 1, 2 and 3 exclusively made use of features derived from arterial, portovenous and equilibrium phases respectively. Methods 4 and 5 made use of the comparatively significant features to attain optimal performance. Method 5 achieved the highest accuracy of 87.8% with sensitivity of 73% and specificity of 94%. Texture analysis of tumours on pre-operative MRI can predict presence of MVI in HCC with accuracies of up to 87.8% and can potentially impact clinical management.