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Hepatocellular carcinoma is a highly aggressive malignant tumor. Although the progress of surgical technology has made some achievements in surgical treatment alone, it still fails to significantly improve the long-term survival of patients. Studies have shown that the recurrence rate of hepatocellular carcinoma is extremely high, while microvascular invasion is an important reason for early recurrence and poor prognosis. Therefore, appropriate postoperative adjuvant therapy measures are crucial to improve the survival prognosis of hepatocellular carcinoma patients with microvascular invasion.
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OBJECTIVE@#To investigate the consistency and diagnostic performance of magnetic resonance imaging (MRI) for detecting microvascular invasion (MVI) of hepatocellular carcinoma (HCC) and the validity of deep learning attention mechanisms and clinical features for MVI grade prediction.@*METHODS@#This retrospective study was conducted among 158 patients with HCC treated in Shunde Hospital Affiliated to Southern Medical University between January, 2017 and February, 2020. The imaging data and clinical data of the patients were collected to establish single sequence deep learning models and fusion models based on the EfficientNetB0 and attention modules. The imaging data included conventional MRI sequences (T1WI, T2WI, and DWI), enhanced MRI sequences (AP, PP, EP, and HBP) and synthesized MRI sequences (T1mapping-pre and T1mapping-20 min), and the high-risk areas of MVI were visualized using deep learning visualization techniques.@*RESULTS@#The fusion model based on T1mapping-20min sequence and clinical features outperformed other fusion models with an accuracy of 0.8376, a sensitivity of 0.8378, a specificity of 0.8702, and an AUC of 0.8501 for detecting MVI. The deep fusion models were also capable of displaying the high-risk areas of MVI.@*CONCLUSION@#The fusion models based on multiple MRI sequences can effectively detect MVI in patients with HCC, demonstrating the validity of deep learning algorithm that combines attention mechanism and clinical features for MVI grade prediction.
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Humans , Carcinoma, Hepatocellular , Retrospective Studies , Liver Neoplasms , Magnetic Resonance Imaging , AlgorithmsABSTRACT
Abstract The power of computed tomography (CT) radiomics for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) demonstrated in current research is variable. This systematic review and meta-analysis aim to evaluate the value of CT radiomics for MVI prediction in HCC, and to investigate the methodologic quality in the workflow of radiomics research. Databases of PubMed, Embase, Web of Science, and Cochrane Library were systematically searched. The methodologic quality of included studies was assessed. Validation data from studies with Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) statement type 2a or above were extracted for meta-analysis. Eleven studies were included, among which nine were eligible for meta-analysis. Radiomics quality scores of the enrolled eleven studies varied from 6 to 17, accounting for 16.7%-47.2% of the total points, with an average score of 14. Pooled sensitivity, specificity, and Area Under the summary receiver operator Characteristic Curve (AUC) were 0.82 (95% CI 0.77-0.86), 0.79 (95% CI 0.75-0.83), and 0.87 (95% CI 0.84-0.91) for the predictive performance of CT radiomics, respectively. Meta-regression and subgroup analyses showed radiomics model based on 3D tumor segmentation, and deep learning model achieved superior performances compared to 2D segmentation and non-deep learning model, respectively (AUC: 0.93 vs. 0.83, and 0.97 vs. 0.83, respectively). This study proves that CT radiomics could predict MVI in HCC. The heterogeneity of the included studies precludes a definition of the role of CT radiomics in predicting MVI, but methodology warrants uniformization in the radiology community regarding radiomics in HCC.
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Objective:To develop and validate a nomogram model for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) based on preoperative enhanced computed tomography imaging features and clinical data.Methods:The clinical data of 210 patients with HCC undergoing surgery in the Second Affiliated Hospital of Anhui Medical University from May 2018 to May 2022 were retrospectively analyzed, including 172 males and 38 females, aged (59±10) years old. Patients were randomly divided into the training group ( n=147) and validation group ( n=63) by systematic sampling at a ratio of 7∶3. Preoperative enhanced computed tomography imaging features and clinical data of the patients were collected. Logistic regression was conducted to analyze the risk factors for HCC with MVI, and a nomogram model containing the risk factors was established and validated. The diagnostic efficacy of predicting MVI status in patients with HCC was assessed by receiver operating characteristic (ROC) curve, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) of the subjects in the training and validation groups. Results:The results of multifactorial analysis showed that alpha fetoprotein ≥400 μg/ml, intra-tumor necrosis, tumor length diameter ≥3 cm, unclear tumor border, and subfoci around the tumor were independent risk factors predicting MVI in HCC. A nomogram model was established based on the above factors, in which the area under the curve (AUC) of ROC were 0.866 (95% CI: 0.807-0.924) and 0.834 (95% CI: 0.729-0.939) in the training and validation groups, respectively. The DCA results showed that the predictive model thresholds when the net return is >0 ranging from 7% to 93% and 12% to 87% in the training and validation groups, respectively. The CIC results showed that the group of patients with predictive MVI by the nomogram model are highly matched with the group of patients with confirmed MVI. Conclusion:The nomogram model based on the imaging features and clinical data could predict the MVI in HCC patients prior to surgery.
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Objective:To analyze the value of laminin γ2 (LAMC2) in the diagnosis of hepatocellular carcinoma (HCC) and the difference in patients with different types of microvascular invasion (MVI).Methods:A cohort of 100 patients with HCC who underwent surgical treatment at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital from January 2021 to March 2022 were prospectively enrolled. There were 80 males and 20 females, aged (55.7±11.1) years. The data of 17 patients with hepatic hemangioma without cirrhosis who underwent operation at the same hospital during the study period were collected to serve as the control group (6 males, 11 females), aged (42.8±9.8) years. LAMC2 in serum was determined by enzyme linked immunosorbent assay. The levels of alpha-fetoprotein (AFP) and LAMC2 were compared between the two groups, and receiver operating characteristic (ROC) curves were drawn to compare these two markers in the diagnosis of HCC. The LAMC2 of different MVI patients were compared.Results:The levels of LAMC2 and AFP were 1 334.2(838.9, 2 656.0) pg/ml and 19.0(4.6, 778.6) μg/L in the HCC group, which were significantly higher than 375.2(221.2, 691.7)pg/ml and 3.3(2.5, 3.5) μg/L in the control group ( Z=-4.32, -4.63, both P<0.001). The areas under the ROC curve were 0.829(95% CI: 0.748-0.892) for LAMC2 and 0.852(95% CI: 0.769-0.910) for AFP, and was 0.949(95% CI: 0.911-0.988) for using both in the diagnoses. The diagnostic efficacy of combining LAMC2 and AFP was significantly better than that of LAMC2 alone and AFP alone (area under ROC: Z=3.15, 3.07, P=0.002, 0.002). When the patients were divided into the M0 group (61 patients), the M1 Group (25 patients) and the M2 Group (14 patients) based on MVIs, the concentrations of LAMC2 were 1 168.6(834.3, 2 521.4) pg/ml, 942.2(614.0, 2 056.6) pg/ml and 3 128.4(1 852.7, 7 191.3) pg/ml, respectively. The level of LAMC2 in the M2 group was significantly higher than that in the M0 and M1 groups ( Z=-3.46, -3.32, P=0.001, 0.004). Conclusion:The diagnostic efficacy of LAMC2 combined with AFP for HCC was significantly higher than that of either LAMC2 alone or AFP alone. Serum LAMC2 levels were significant different among the groups of HCC patients with different types of MVI.
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Objective:To explore the risk factors of microvascular invasion (MVI) in hepatocellular carcinoma (HCC), and to predict MVI preoperatively, non-invasively and accurately.Methods:A total of 150 HCC patients (183 HCC lesions) were retrospectively collected in the First Affiliated Hospital of Xi′an Jiaotong University from January 2016 to June 2022.The clinical data and hematological data, gray-scale ultrasonography (US), contrast-enhanced ultrasonography (CEUS), enhanced magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (EOB-MRI) and pathological data of these patients were recorded. According to the pathological diagnosis of MVI, the lesions were divided into MVI (+ ) group and MVI (-) group. The indicators between the two groups were compared. All 183 lesions were put into the training set, and the prediction model with nomogram was constructed according to the risk factors of MVI selected by multivariate Logistic regression. The internal verification was carried out by ten-fold cross-validation method.Results:There were significant statistical differences in the following parameters between MVI (+ ) group ( n=109) and MVI (-) group ( n=74) (all P<0.05). These were cirrhosis, serological parameters (alpha-fetoprotein, albumin, total bilirubin), qualitative indexes of US (size, boundary, internal echo), qualitative indexes of CEUS (hyper/iso/hypovascularity of lesions in arterial phase, portal phase, and delayed phase compared with hepatic parenchyma), and quantitative indexes of EOB-MRI [post enhancement rate (post ratio) and gadolinium disodium rate (EOB ratio)] calculated mainly in terms of lesions and surrounding liver parenchyma in hepatobiliary phase and unenhanced T1 images). Finally, cirrhosis of patients, the size, boundary, internal echo of lesions in US; arterial phase (AP), portal phase (PP), post-vascular phase (PVP) features in CEUS; the EOB rate and post rate of EOB-MRI entered the prediction model of MVI. The training set exhibited good calibration and net gain rate. The areas under the ROC curve for the training set and the validation set were 0.981 and 0.961, respectively, while the diagnostic accuracy were 92.9% and 85.8%, respectively. Conclusions:The model constructed mainly by multimodality imaging methods can achieve favorable predictive performance for MVI, which provides valuable ideas for noninvasively predicting the incidence of MVI and optimizing the MVI-related treatment of MVI in HCC patients.
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Hepatectomy and liver transplantation are the most effective radical treatment for patients with hepatocellular carcinoma, but the high recurrence rate after surgery which seriously affects the prognosis of patients cannot be ignored. Microvascular invasion (MVI) is a risk factor for postoperative recurrence and metastasis in patients with hepatocellular carcinoma. There is no consensus or guideline recommendation locally or intermutually on postoperative adjuvant therapy of patients with hepatocellular carcinoma with MVI. Appropriate selection of postoperative adjuvant therapy is worth more in-depth discussion. This article reviews recent and relevant studies on postoperative adjuvant therapy for patients with hepatocellular carcinoma and MVI, including local anti-tumor therapy, systemic chemotherapy, immunotherapy, targeted therapy and combination therapy, with the aim to provide better reference to clinicians in managing these patients with postoperative adjuvant therapy.
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Objective:To evaluate the effect of microvascular invasion (MVI) on postoperative prognosis of microhepatocellular carcinoma by a meta-analysis system.Methods:Relevant literatures in PubMed, Cochrane Library, Embase, CNKI, VIP and Wanfang databases were systematically searched. The search period was from January 2012 to January 2022. The Chinese search terms were "liver cancer" , "hepatocellular carcinoma" , "2 cm" , "microvascular invasion" , and "prognosis" . The English search terms were "small" , "solitary small" , "up to 2 cm" , "< 2 cm" , "liver" , "hepatocellular carcinoma" , "microvascular invasion" . The differences in prognosis of patients with microhepatocellular carcinoma in MVI(+ ) group and MVI(-) group were compared. Meta-analysis was performed using Review Manager 5.4 software.Results:Finally, 7 articles were included in the systematic review, with a total of 1 319 patients. All included literatures were scored ≥7 on the modified Newcastle-Ottawa scale. The results of meta-analysis showed that there were no significant differences in 1-year overall survival (OS) between MVI(+ ) group and MVI(-) group ( OR=3.14, 95% CI: 0.92-10.72, P=0.068). The 5-year OS time of patients in the MVI(+ ) group was shorter than that in the MVI(-) group, and the differences were statistically significant ( OR=2.34, 95% CI: 1.62-3.36, P<0.001). The 1-year and 5-year disease-free survival of the MVI(-) group were better than those of the MVI(+ ) group, and the difference was statistically significant (1-year: OR=3.09, 95% CI: 1.75-5.44, P<0.001; 5 years: OR=1.76, 95% CI: 1.24-2.51, P=0.002). Conclusion:The 5-year and long-term survival of MVI(+ ) patients with microhepatocellular carcinoma was poor, and the postoperative recurrence rate was high.
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Objective:To establish a clinical diagnostic scoring model for preoperative predicting hepatocellular carcinoma (HCC) microvascular invasion (MVI) based on gadolinium-ethoxybenzyl-diethylenetriamine pentacetic acid (Gd-EOB-DTPA) enhanced MRI, and verify its effectiveness.Methods:From January 2014 to December 2020, a total of 251 cases with pathologically confirmed HCC from Tianjin First Central Hospital and Jilin University First Hospital were retrospectively collected to serve as the training set, while 57 HCC patients from Tianjin Medical University Cancer Hospital were recruited as an independent external validation set. The HCC patients were divided into MVI positive and MVI negative groups according to the pathological results. The tumor maximum diameters and apparent diffusion coefficient (ADC) values were measured. On the Gd-EOB-DTPA MRI images, tumor morphology, peritumoral enhancement, peritumoral low intensity (PTLI), capsule, intratumoral artery, intratumoral fat, intratumoral hemorrhage, and intratumoral necrosis were observed. Univariate analysis was performed using the χ 2 test or the independent sample t-test. The independent risk factors associated with MVI were obtained in the training set using a multivariate logistic analysis. Points were assigned to each factor according to the weight value to establish a preoperative score model for predicting MVI. The receiver operating characteristic (ROC) curve was used to determine the score threshold and to verify the efficacy of this scoring model in predicting MVI in the independent external validation set. Results:The training set obtained 98 patients in the MVI positive group and 153 patients in the MVI negative group, while the external validation set obtained 16 patients in the MVI positive group and 41 patients in the MVI negative group. According to logistic analysis, tumor maximum diameter>3.66 cm (OR 3.654, 95%CI 1.902-7.018), hepatobiliary PTLI (OR 9.235, 95%CI 4.833-16.896) and incomplete capsule (OR 6.266, 95%CI 1.993-9.345) were independent risk factors for MVI in HCC, which were assigned scores of 3, 4 and 2, respectively. The total score ranged from 0 to 9. In the external validation set, ROC curve analysis showed that the area under the curve of the scoring model was 0.918 (95%CI 0.815-0.974, P=0.001). When the score>4 was used as the threshold, the accuracy, sensitivity, and specificity of the model in predicting MVI were 84.2%, 81.3%, and 85.4%, respectively. Conclusions:A scoring model based on Gd-EOB-DTPA-enhanced MRI provided a convenient and reliable way to predict MVI preoperatively.
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Objective:To investigate the long-term outcome of centrally located hepatocellular carcinoma with microvascular invasion(MVI)after radical resection.Methods:A retrospective cohort study was used to collect and analyze the clinical and pathological data of 81 patients with centrally located HCC who underwent surgery in the Cancer Hospital Chinese Academy of Medical Sciences from January 2016 to January 2018. According to the classification of MVI, patients were divided into 41 low-level group (MVI M1) and 40 high-level group (MVI M2). The 1, 3, 5-year OS and relapse free survival were calculated in all patients. The main outcomes were overall survival (OS), disease-free survival (DFS) and postoperative complications. OS and DFS of patients was estimated using Kaplan-Meier method and the difference between groups was assessed using Log-rank test. COX proportional-hazards regression models were used to estimate the association between exposure factors and prognosis. The measurement data of normal distribution were expressed by mean±standard deviation ( ± s), and t-test was used for comparison between the two groups. Measurement data with non-normal distribution were represented by M ( Q1, Q3), and rank sum test was used for comparison between the two groups.Chi-square test was used for comparison between the two groups of count data. Results:The 1-, 3-, 5-year OS and relapse free survival were 88%, 76%, 73%, and 57%, 42%, 27% for all 81 centrally located HCC patients, respectively. The DFS and OS of the MVI M1 group were 26(11, 39) months and 36(25, 53) months, respectively, and the MVI M2 group were 9(4, 29) months and 22(10, 45)months, respectively, and the difference was statistically significant ( P<0.05). In survival analysis, OS and DFS was significantly different in MVI M1 group compared with that in MVI M2 group ( HR=4.69, 95% CI: 1.539-14.286, P=0.0027; HR=1.92, 95% CI: 1.111-3.333, P=0.016). The incidence of postoperative mild complications in the MVI M1 group and the MVI M2 group was 95.1% and 90.0%, respectively. There was no significant difference between the two groups ( P=0.379). Cox analysis showed that MVI M2 was the independent prognostic factors for centrally located HCC in OS and DFS ( P<0.05). Conclusion:Surgical treatment for centrally located HCC with MVI is safe and effective, and MVI classification is an independent risk factor for its prognosis.
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ABSTRACT Objectives: Non-small cell lung cancer (NSCLC) is an incidental and aggressive type of cancer. Although curative treatment can be offered, the recurrence rate is relatively high. Identifying factors that have a prognostic impact may guide changes in the staging system and recommendations for adjuvant therapy. The aim of this study was to evaluate the impact of microvascular invasion on the 5-year overall survival (OS) of patients with resected NSCLC treated at a reference cancer center. Methods: This retrospective, observational cohort study included patients diagnosed with early-stage NSCLC (clinical stages I-IIIA), treated with curative-intent surgery at the Brazilian National Cancer Institute between 2010 and 2016. Results: The dataset comprised 91 surgical patients, mostly females and white, with a mean age of 62 years (range between 29-83). Cases were distributed as stages I, II, and III in 55%, 29%, and 16%. Adenocarcinoma was the predominant histological subtype (67%), and microvascular invasion was present in 25% of the patients. The 5-year OS probability was 60% (95% CI, 48.3-68.9). Among all characteristics, advanced stages (p = 0.001) and the presence of microvascular invasion (p< 0.001) were related to a worse 5-year OS. After adjusting for age group and pathological stage, the presence of microvascular invasion was associated with a 4-fold increased risk of death (HR 3.9, 95% CI, 1.9-8.2). Conclusion: The presence of microvascular invasion was an independent factor related to worse survival and, therefore, should be routinely assessed in resected specimens.
RESUMO Objetivos: O câncer de pulmão não pequenas células (CPNPC) é um tipo incidental e agressivo de câncer. Embora o tratamento curativo possa ser oferecido, a taxa de recidiva é relativamente alta. A identificação de fatores que têm impacto prognóstico pode orientar mudanças no TNM e recomendações para terapia adjuvante. O objetivo deste estudo foi avaliar o impacto da invasão microvascular na sobrevida global (SG) em 5 anos de pacientes com CPNPC ressecado tratados em um centro de referência em câncer. Métodos: Este estudo de coorte retrospectivo e observacional incluiu pacientes diagnosticados com CPNPC em estágio inicial (estágios clínicos I-IIIA), tratados com cirurgia com intenção curativa no Instituto Nacional de Câncer entre 2010 e 2016. Resultados: Foram incluídos 91 pacientes tratados com cirurgia, a maioria mulheres e brancos, com média de idade de 62 anos (variação entre 29-83). Os casos foram distribuídos em estágios I, II e IIIA em 55%, 29% e 16%. Adenocarcinoma foi o subtipo histológico predominante (67%), e a invasão microvascular esteve presente em 25% dos pacientes. A probabilidade de SG em 5 anos foi de 60% (IC 95%, 48,3-68,9). Dentre todas as características analisadas, estágios mais avançados (p = 0,001) e a presença de invasão microvascular (p < 0,001) foram relacionados a uma pior SG em 5 anos. Após ajustar para faixa etária e estágio patológico, a presença de invasão microvascular foi associada a um aumento de 4 vezes no risco de morte (RR 3,9, IC 95%, 1,9-8,2). Conclusão: A presença de invasão microvascular foi um fator independente relacionado a uma pior sobrevida e, portanto, deve ser avaliada rotineiramente em espécimes ressecados.
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Objective:To investigate the patients with hepatocellular carcinoma suitable for transcatheter arterial chemoembolization (TACE) after radical resection who were screened based on microvascular invasion (MVI) and Ki-67 expression.Methods:Of 400 patients with hepatocellular carcinoma who underwent radical resection in the Affiliated Hospital of Qingdao University from January 2013 to December 2019 were included and analyzed retrospectively, including 324 males and 76 females, aged (59.7±9.8) years, ranging from 32 to 87 years. According to whether they received adjuvant TACE treatment after operation, they were divided into simple operation group ( n=210) and TACE + operation group ( n=190). The recurrence in the first year after operation was followed up by outpatient reexamination. Univariate and multivariate Cox regression analysis were used to analyze the influencing factors of recurrence free survival after surgical resection. Subgroup analysis was performed according to Ki-67 and MVI to compare the recurrence free survival. Results:Multivariate Cox regression analysis showed that patients with proportion of Ki-67 positive cells ≥27.5% ( HR=2.073, 95% CI: 1.433-3.000, P<0.001) and MVI positive ( HR=2.339, 95% CI: 1.584-3.456, P<0.001) had increased risk of recurrence after radical resection. The 1-year cumulative recurrence free survival rate in the simple operation group was 70.0%, and there was no significant difference compared with 67.9% in the operation + TACE group( χ 2=0.08, P=0.774). Subgroup analysis: in the low expression of Ki-67 combined with negative MVI group ( n=128), the cumulative recurrence free survival rate of one year after operation in the simple operation group ( n=84) was 91.7%, which was significantly higher than 72.7% in the operation + TACE group ( n=44)( χ 2=8.22, P=0.004). There was no significant difference in the 1-year cumulative recurrence free survival rate between the simple operation group and the operation + TACE group (both P>0.05) in patients of Ki-67 high expression combined with MVI negative or Ki-67 low expression combined with MVI positive. In the Ki-67 high expression combined with MVI positive group ( n=107), the cumulative one-year recurrence free survival rate in the simple operation group ( n=62) was 40.3%, which was significantly lower than 60.0% in the operation + TACE group ( n=45)(χ 2=4.22, P=0.040). Conclusion:High expression of Ki-67 (≥27.5%) combined with positive MVI are the prediction factors for postoperative TACE treatment. Low expression Ki-67 (<27.5%) combined with negative MVI was contraindicated for postoperative TACE treatment.
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Objective:To investigate the application value of peripheral blood circulating tumor cell (CTC) classification in the prediction of preoperative microvascular invasion of hepato-cellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinico-pathological data of 102 HCC patients who were admitted to Zhengzhou University People's Hospital from September 2018 to September 2020 were collected. There were 71 males and 31 females, aged from 29 to 80 years, with a median age of 57 years. Observation indicators: (1) surgical situations; (2) results of CTC detection and microvascular invasion in HCC patients; (3) results of CTC classification and the best cut-off value of CTC classification in the prediction of microvascular invasion in HCC; (4) influencing factors for microvascular invasion in HCC; (5) comparison of clinicopathological features in HCC patients with different cell counts in mesenchymal phenotype of CTC (M-CTC). Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was analyzed using the nonparametric rank sum U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. The receiver operating characteristic (ROC) curve was used to determine the best cut-off value for the risk of microvascular invasion in patients. Univariate and multivariate analysis were performed using the Logistic regression model. Results:(1) Surgical situations. All 102 patients underwent surgery successfully, including 17 cases undergoing local hepatectomy, 43 cases under-going segmentectomy, 22 cases undergoing hepatic lobectomy, 13 cases undergoing hemilectomy and 7 cases undergoing enlarged hemilectomy. The operation time and the volume of intraoperative blood loss were 235(147,293)minutes and 300(110,500)mL of the 102 patients, respectively. (2) Results of CTC detection and microvascular invasion in HCC patients. Of 102 patients, there were 36 casas with epithelial phenotype of CTC (E-CTC), 86 cases with hybrid phenotype of CTC (H-CTC), 30 cases with M-CTC, respectively, and the total CTC (T-CTC) were positive in 89 cases. Results of postoperative pathological examination showed that there were 40 cases with micro-vascular inva-sion and 62 cases without microvascular invasion in the 102 patients. Of the 40 patients with micro-vascular invasion, the count of E-CTC, H-CTC, M-CTC and T-CTC were 0(0,1) per 5 mL, 4(2,5) per 5 mL, 1(0,2) per 5 mL and 5(3,8) per 5mL, respectively. The above indicators of the 62 cases without microvascular invasion were 0(0,1) per 5 mL, 3(1,5) per 5 mL, 0(0,0) per 5 mL and 3(2,6) per 5 mL, respectively. There were significant differences in the count of M-CTC and T-CTC between patients with and without microvascular invasion ( Z=-4.83, -2.96, P<0.05). (3) Results of CTC classi-fication and the best cut-off value of CTC classification in the prediction of microvascular invasion in HCC. The ROC curve showed that best cut-off value of M-CTC and T-CTC counts in the prediction of microvascular invasion in HCC were 1 per 5 mL and 4 per 5 mL, respectively, with the area under curve, the corresponding specificity, sensitivity were 0.70 (95% confidence interval as 0.60-0.81, P<0.05), 75.8%, 62.9% and 0.67 (95% confidence interval as 0.57-0.78, P<0.05), 60.0%, 72.5%, respec-tively. (4) Influencing factors for microvascular invasion in HCC. Result of univariate analysis showed that alpha fetoprotein (AFP), aspartate aminotransferase (AST), tumor diameter, tumor number, tumor margin, Barcelona clinic liver cancer staging, M-CTC counts and T-CTC counts were related factors influencing microvascular invasion in HCC ( odds ratio=3.13, 0.43, 4.92, 5.65, 2.54, 2.93, 8.25, 4.47, 95% confidence interval as 1.34-7.33, 0.19-0.98, 2.09-11.58, 2.35-13.63, 1.13-5.75, 1.27-6.74, 3.13-21.75, 1.88-10.61, P<0.05). Result of multivariate analysis showed that tumor diameter >5 cm, tumor number as multiple and M-CTC counts ≥1 per 5 mL were independent risk factors influencing microvascular invasion in HCC ( odds ratio=2.97, 4.14, 4.36, 95% c onfidence interval as 1.01-8.70, 1.14-15.02, 1.36-13.97, P<0.05). (5) Comparison of clinicopathological features in HCC patients with different cell counts in M-CTC. The 102 HCC patients were divided into the high M-CTC group of 30 cases with M-CTC counts ≥1 per 5 mL and the low M-CTC group of 72 cases with M-CTC counts <1 per 5 mL, according to the best cut-off value of M-CTC counts. Cases with hepatitis, cases with AFP >400 μg/L, cases with AST >35 U/L, cases with irregular tumor margin, cases with tumor diameter >5 cm, cases with tumor number as multiple and cases with micro-vascular invasion were 22, 17, 13, 21, 18, 16 and 22 in the high M-CTC group of 30 cases. The above indicators were 35, 18, 48, 26, 25, 21 and 18 in the low M-CTC group of 72 cases. There were significant differences in the above indicators between the high M-CTC group and the low M-CTC group ( χ2=5.25, 9.42, 4.80, 9.79, 5.55, 5.35, 20.75, P<0.05). Conclusions:The epithelial-mesen-chymal phenotype of peripheral blood CTC can be used to predict the preoperative microvascular invasion in HCC. Tumor diameter >5 cm, tumor number as multiple and M-CTC counts ≥1 per 5 mL are independent risk factors influencing microvascular invasion in HCC patients.
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Objective:To evaluate radiofrequency ablation-assisted liver resection on early recurrence of hepatocellular carcinoma(HCC) with microvascular invasion (MVI).Methods:A total of 82 HCC patients from Jun 2015 to Jun 2020 were divided into assisted group ( n=41) and control group ( n=41) after local hepatectomy.And by pathology,both groups were further substratified into with or without MVI subgroups. Results:There was no statistically significant difference in the baseline data between two groups,nor there was difference in recurrence-free survival rate between the two groups ( χ 2=0.177, P=0.674). However, by subgroup analysis, the recurrence-free survival rate of ablation assisted group was higher than that of the simple local hepatectomy group among MVI positive patients ( χ 2=5.096, P = 0.024).Multivariate analysis showed that only tumor diameter ( HR=1.32, 95% CI: 1.02-1.72, P=0.036) was an independent risk factor for local recurrence at the incisal margin, while mode of operation ( HR=0.15 ,95% CI: 0.04-0.52 ,P=0.003) and MVI ( HR=8.65 ,95% CI: 2.19-34.19 ,P=0.002) were independent risk factors for intrahepatic distant metastasis. Conclusion:Local hepatectomy assisted by intraoperative radiofrequency ablation on hepatic cross section could effectively reduce the postoperative early recurrence rate for hepatocellular carcinoma patients with MVI.
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Vascular invasion and systemic immune-inflammation index (SII) are risk factors for the prognosis of patients with hepatocellular carcinoma. At present, the correlation between the two is not clear. This meta-analysis explored the relationship between preoperative SII and vascular invasion in patients with hepatocellular carcinoma. According to the search formula, the Pubmed, Embase, Cochrane, Web of Science, and CNKI databases were searched for the relevant research until March 2020. After the quality evaluation of the included literature, the odds ratio (OR) and its corresponding 95% confidence interval (CI) were used as the effect measure. Stata 15. 0 software was used for statistical analysis. The meta-analysis eventually included seven retrospective cohort studies of 3583 patients with hepatocellular carcinoma. The results showed that the choice of SII cut-off value affects SII's efficiency in predicting the risk of vascular invasion. In the cohort of studies with appropriate SII cut-off value, the high SII preoperative group had a higher risk of vascular invasion (OR=2.62; 95%CI: 2.07-3.32; P=0.000) and microvascular invasion (OR=1.82; 95%CI: 1.01-3.25; P=0.045) than the low SII group. The tumor diameter (OR=2.88; 95%CI: 1.73-4. 80; P=0.000) of the high SII group was larger than that of the low SII group. There was no publication bias in this study (Begg's test, P=0.368). As a routine, cheap, and easily available index, SII can provide a certain reference value for clinicians to evaluate vascular invasion before operation.
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Humans , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Retrospective Studies , Risk Factors , InflammationABSTRACT
Objective:To study the predictive value of combining ultrasound elestography with serological examination on incidences of microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC).Methods:The clinical data of 288 patients with HCC who underwent liver resection at MengChao Hepatobiliary Hospital of Fujian Medical University from January 2018 to September 2020 were retrospectively analyzed. 104 MVI-negative and 184 MVI-positive patients who were confirmed by postoperative histopathology were divided into the MVI-negative and MVI-positive groups respectively. Serological indicators of alanine aminotransferase, aspartate aminotransferase, platelet, albumin, and alpha-fetoprotein were compared between groups. Imaging indexes including elasticity at liver tumor surrounding 1 cm area (S1), elasticity at liver tumor surrounding 2 cm area (S2), S1S2index (S1/S2×10) and longest tumor diameter were compared between groups. Multi-variate analysis was used to screen out independent risk factors in predicting MVI of hepatocellular carcinoma, and then a nomogram model was constructed.Results:Of 288 patients with HCC who met the inclusion criteria of this study, there were 225 males and 63 females, aged (56.3±9.7) years. Multivariate logistic regression analysis revealed that patients with HCC who had multiple tumors ( OR=2.47, 95% CI: 1.41-4.33, P=0.002), long tumor diameter ( OR=1.21, 95% CI: 1.08-1.36, P=0.031), AFP>400 μg/L ( OR=2.83, 95% CI: 1.54-5.22, P=0.015), a high S1S2index ( OR=1.33, 95% CI: 1.17-1.51, P=0.025) had high incidences of MVI. The nomogram model constructed from these risk factors showed the risk of MVI in HCC patients with a mean absolute deviation of compliance between the predicted value and the true value being 0.021. The receiver operating characteristic (ROC) curve showed that the area under ROC curve of the nomogram model which predicted MVI of HCC patients was 0.777 (95% CI: 0.720-0.835). Conclusions:Multiple tumors, long tumor diameter, AFP>400 μg/L and a high S1S2 index were independent risk factors for MVI in HCC patients. The nomogram model established by these factors accurately predicted the risk of MVI and provided a reference for better choice of treatment.
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Objective:To explore the value of different machine learning models based on Gd-EOB-DTPA enhanced MRI hepatobiliary phase radiomics features in preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC).Methods:The data of 132 patients with HCC confirmed by pathology in the First Affiliated Hospital of Soochow University from January 2015 to May 2020 were retrospectively analyzed, including 72 cases of positive MVI and 60 cases of negative MVI. According to the proportion of 7∶3, the cases were randomly divided into training set and validation set. The radiomics features of hepatobiliary phase images for HCC were extracted by PyRadiomics software. The clinical and radiomics features of the training set were screened by the least absolute shrinkage and selection operator (LASSO) regression with 5 fold cross-validation, and then the optimal feature subset was obtained. Six machine learning algorithms, including decision tree, extreme gradient boosting, random forest, support vector machine (SVM), generalized linear model (GLM) and neural network, were used to build the prediction models, and the ROC curves were used to evaluate the prediction ability of the models. DeLong test was used to compare the differences of area under the curve (AUC) for 6 machine learning algorithms.Results:Totally 14 features selected by LASSO regression were obtained to form the optimal feature subset, including 2 clinical features (maximum tumor diameter and alpha-fetoprotein) and 12 radiomics features. The AUCs of decision tree, extreme gradient boosting, random forest, SVM, GLM and neural network based on the optimal feature subset were 0.969, 1.000, 1.000, 0.991, 0.966, 1.000 in the training set and 0.781, 0.890, 0.920, 0.806, 0.684, 0.703 in the validation set, respectively. There were significant differences in the AUCs between extreme gradient boosting and GLM or neural network ( Z=2.857, 3.220, P=0.004, 0.001). The differences in AUCs between random forest and SVM, GLM, or neural network were significant ( Z=2.371, 3.190, 3.967, P=0.018, 0.001,<0.001). The difference in AUCs between SVM and GLM was statistically significant ( Z=2.621 , P=0.009). There were no significant differences in the AUCs among the other machine learning models ( P>0.05). Conclusion:Machine learning models based on Gd-EOB-DTPA enhanced MRI hepatobiliary phase radiomics features can be used to preoperatively predict MVI of HCC, particularly the extreme gradient boosting and random forest models have high prediction efficiency.
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Objective:To explore the efficacy of precision hepatectomy in the treatment of single hepatocellular carcinoma with microvascular invasion (MVI) of and the risk factors of positive incisal margin after operation.Methods:The clinical data of 212 patients with single hepatocellular carcinoma with MVI treated in Affiliated Hospital of Panzhihua University from July 2016 to July 2019 were analyzed retrospectively. 152 patients were treated with precision hepatectomy and 60 patients with traditional hepatectomy. According to the pathological results of postoperative liver resection, the patients treated with precision hepatectomy were divided into two groups: negative group ( n=129) and positive group ( n=23). The operation-related indexes, postoperative complications and disease-free survival rate of precision hepatectomy and traditional hepatectomy were compared, and the general data of patients with negative and positive liver cutting edge were compared. multivariate analysis of the factors affecting the positive liver cutting edge after operation; to construct a line chart prediction model to predict the positive liver cutting edge after operation, and to evaluate its predictive efficiency. Normally distributed measurement data are represented by mean±standard deviation ( Mean± SD), independent t-test is used for comparison between groups; count data are represented by the number of cases and percentages, and χ2 test is used for comparison between groups. Results:The operative time, intraoperative blood loss, postoperative hospital stay, positive rate of surgical margin, total incidence of postoperative complications, AFP negative conversion rate 6 months after operation, and 1-year disease-free survival rate of precision hepatectomy were (328.62±38.74) min, (496.83±59.76) mL, (15.28±3.61) d, 15.13% (23/152), 3.95% (6/152), 81.58% (124/152), 67.11% (102/152), respectively. The mean values of traditional hepatectomy were (315.29±40.95) min, (681.46±58.27) mL, (23.87±4.65) d, 28.33% (17/60), 21.67% (13/60), 66.67% (40/60) and 46.67% (28/60), respectively, the difference was statistically significant ( P<0.05). Univariate analysis showed that the positive liver resection margin after precision liver resection was related to the maximum diameter of the tumor, vascular tumor thrombus, TNM staging, BCLC staging, liver cirrhosis, AFP 2 months after surgery, and the distance between the tumor and the resection margin ( OR=3.645, 5.248, 4.285, 4.462, 3.883, 3.964, 3.872; 95% CI: 2.875-4.415, 4.426-6.070, 3.271-5.299, 3.354-5.570, 3.062-4.704, 3.248-4.680, 2.987-4.757; P<0.05). Maximum tumor diameter >5 cm, vascular tumor thrombus, TNM stage Ⅲ, BCLC stage C, liver cirrhosis, postoperative AFP ≥20 μg Uniql, the distance between the tumor and the resection margin was <1 mm were the risk factors of positive incisal margin after precision hepatectomy in patients with single liver cancer with MVI( OR=6.685, 8.425, 7.758, 7.854, 7.124, 7.246, 6.926; 95% CI: 5.828-7.542, 7.6385-9.212, 6.926-8.590, 7.062-8.646, 6.583-7.665, 6.618-7.874, 6.028-7.824; P<0.05). The constructed line chart prediction model had better differentiation and higher accuracy. Conclusions:Precision hepatectomy in the treatment of single hepatocellular carcinoma with MVI has the advantages of less intraoperative bleeding, faster postoperative recovery, less postoperative complications, low positive rate of liver incisal margin and high disease-free survival rate. The construction of a risk prediction model with positive surgical margin provides a reference for improving the survival rate of patients in clinic.
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Objective:To study the use of perfluorobutane contrast-enhanced ultrasound (CEUS) in preoperative detection of microvascular invasion (MVI), and postoperative short-term recurrence of hepatocellular carcinoma (HCC).Methods:Patients who underwent hepatectomy with curative intent at the Chinese PLA General Hospital from January 2021 to April 2021 were prospectively enrolled into this study. Of 42 patients in this study, there were 36 males and 6 females, with age of (56.51±11.95) years old. All patients underwent preoperative perfluorobutane CEUS, and the characteristics of ultrasound, the vascular phase and Kupffer phase of perfluorobutane CEUS were recorded. Based on the pathological results, these patients were divided into the MVI and non-MVI groups. These patients underwent liver MRI once every 3 months postoperatively to diagnose tumor recurrence. According to the recurrence of HCC 6 months after operation, these patients were divided into the non-recurrence and the recurrence groups. Independent risk factors for MVI and short-term recurrence were analyzed by univariate and multivariate analyses.Results:Two patients had two lesions, and the remaining 40 patients had a single lesion. The pathological diagnosis of all the lesions were HCC (14 patients in the MVI group and 28 patients in the non-MVI group). The median follow-up was 6 (3, 6) months, and there were 8 patients in the recurrence group and 34 patients in the non-recurrence group. On logistic analysis, independent risk factors for MVI included the number of vessels detected on color Doppler flow imaging (CDFI) ( OR=5.762, 95% CI: 1.597-20.785, P=0.007), increased tumor size by more than 10% after CEUS arterial enhancement ( OR=10.186, 95% CI: 3.647-28.447, P=0.037), and thickness of corona enhancement at Kupffer phase of greater than 5 mm ( OR=17.340, 95% CI: 6.124-49.095, P=0.040). Cox regression showed the independent risk factors for short-term recurrence to include the number of vessels in CDFI ( RR=7.519, 95% CI: 1.086-52.051, P=0.041) and thickness of corona enhancement at Kupffer phase of greater than 5 mm ( RR=10.623, 95% CI: 1.265-89.218, P=0.030). Conclusion:Preoperative perfluorobutane CEUS had potential values in detecting MVI and in predicting postoperative short-term recurrence of HCC.
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Objective To evaluate the effect of microvascular invasion (MVI) on prognosis of recipients after liver transplantation for primary liver cancer (liver cancer). Methods Clinical data of 177 recipients after liver transplantation for liver cancer were retrospectively analyzed. All patients were divided into the MVI-positive group (n=64) and MVI-negative group (n=113) according to postoperative pathological examination results. Clinical data were statistically compared of all recipients between the negative and positive MVI groups. The prognosis and risk factors of liver transplantation recipients for liver cancer were analyzed. Results Among 177 recipients, 64 cases (36.2%) were positive for MVI and 113 (63.8%) negative for MVI. Compared with the MVI-negative recipients, MVI-positive recipients had significantly lower degree of tumor differentiation, higher preoperative alpha-fetaprotein (AFP) level, larger maximal tumor diameter, a larger quantity of tumors, more satellite lesions and more recipients who did not meet the Milan criteria (all P < 0.05). The 1-, 3- and 5-year overall survival (OS) and recurrence-free survival (RFS) of recipients after liver transplantation for liver cancer were 80.2%, 62.1%, 58.5% and 66.3%, 57.5%, 51.2%, respectively. The 1-, 3- and 5-year OS and RFS of MVI-positive recipients were 70%, 39%, 35% and 53%, 39%, 33%, significantly lower than 86%, 75%, 72% and 73%, 68%, 63% of their counterparts negative for MVI (all P < 0.05). Cox regression analysis showed that the maximal tumor diameter >8 cm, preoperative AFP level ≥20 ng/mL, low degree of tumor differentiation and positive MVI were the independent risk factors for OS of recipients after liver transplantation for liver cancer (all P < 0.05). Positive MVI, low degree of tumor differentiation and preoperative down-staging failure were the independent risk factors for RFS of recipients after liver transplantation for liver cancer (all P < 0.05). Conclusions MVI is of significant clinical value in predicting clinical prognosis of recipients after liver transplantation for liver cancer.