Evaluation of response in patients with hepatocellular carcinoma treated with intratumoral dendritic cell vaccination using intravoxel incoherent motion (IVIM) MRI and histogram analysis

2021 ◽  
pp. 028418512110659
Author(s):  
Mats Andersson ◽  
Oscar Jalnefjord ◽  
Mikael Montelius ◽  
Magnus Rizell ◽  
Malin Sternby Eilard ◽  
...  

Background Immunotherapy of hepatocellular carcinoma (HCC) is an emerging method with promising results. Immunotherapy can have an antitumor effect without affecting tumor size, calling for functional imaging methods for response evaluation. Purpose To evaluate the response to intratumoral injections with the immune primer ilixadencel in HCCs with diffusion-weighted magnetic resonance imaging (DW-MRI) using intravoxel incoherent motion (IVIM) and histogram analysis. Material and Methods A total of 17 patients with advanced HCC were treated with intratumoral injections with ilixadencel on three occasions 2–5 weeks apart. The patients were examined with IVIM before each injection as well as approximately three months after the first injection. Results The 10th percentile of perfusion-related parameter D* decreased significantly after the first and second intratumoral injections of ilixadencel compared to baseline ( P < 0.05). There was a non-significant trend of lower median region of interest f (perfusion fraction) before injection 2 compared to baseline ( P = 0.07). There were significant correlations between the 10th percentile and median of D at baseline and change in tumor size after three months ( r = 0.79, P < 0.01 and r = 0.72, P < 0.05, respectively). Conclusion DW-MRI with IVIM and histogram analysis revealed significant reductions of D* early after treatment as well as an association between D at baseline and smaller tumor growth at three months. The lower percentiles (10th and 50th) were found more important. Further research is needed to confirm our preliminary findings of reduced perfusion after ilixadencel vaccinations, suggesting a treatment effect on HCC.

2017 ◽  
Vol 58 (12) ◽  
pp. 1448-1456 ◽  
Author(s):  
Mei Yuan ◽  
Yan Zhong ◽  
Yu-Dong Zhang ◽  
Tong-Fu Yu ◽  
Hai Li ◽  
...  

Background Differentiating between malignant and benign solitary pulmonary lesions (SPLs) is challenging. Purpose To determine diagnostic performance of intravoxel incoherent motion-based diffusion-weighted imaging (DW-IVIM) in distinguishing malignant from benign SPLs, using histogram analysis derived whole-tumor and single-section region of interest (ROI). Material and Methods This retrospective study received institutional review board approval. A total of 129 patients with diagnosed SPLs underwent DW-IVIM and apparent diffusion coefficient (ADC). ADC, slow diffusion coefficient (D), fast diffusion coefficient (D*), and perfusion fraction (f) were calculated separately by outlining whole-tumor and single-section ROI. Inter-observer reliability was assessed by inter-class correlation coefficient (ICC). ADC and DW-IVIM parameters were analyzed using independent-sample T-test. Receiver operating characteristic (ROC) analysis was constructed to determine diagnostic performance. Multiple logistic regression was performed to identify independent factors associated with malignant SPLs. Results There were 48 benign SPLs found in 35 patients and 94 patients with lung cancer (LC). ICC for whole-tumor ROI (range, 0.89–0.95) was higher than that for single-section ROI (range, 0.61–0.71). Mean ADC and D were significantly lower in the malignant group. ADC and D 10th showed significantly higher AUC values than did mean ADC and D. D showed significantly higher diagnostic accuracy in mean, 10th, and 25th percentiles than ADC values (all Ps < 0.05). D 10th was found to be an independent factor in discriminating LCs with an odds ratio of –1.217. Conclusion Volumetric analysis had higher reproducibility and diagnostic accuracy than did single-section. Further, compared to ADC, D value differentiated benign SPLs from LCs more accurately.


2020 ◽  
Vol 20 (9) ◽  
pp. 1147-1156
Author(s):  
Hanrui Li ◽  
GeTao Du ◽  
Lu Yang ◽  
Liaojun Pang ◽  
Yonghua Zhan

Background: Hepatocellular carcinoma is cancer with many new cases and the highest mortality rate. Chemotherapy is the most commonly used method for the clinical treatment of hepatocellular carcinoma. Natural products have become clinically important chemotherapeutic drugs due to their great potential for pharmacological development. Many sesquiterpene lactone compounds have been proven to have antitumor effects on hepatocellular carcinoma. Objective: Britanin is a sesquiterpene lactone compound that can be considered for the treatment of hepatocellular carcinoma. The present study aimed to investigate the antitumor effect of britanin. Methods: BEL 7402 and HepG2 cells were used to study the cytotoxicity and antitumor effects of britanin. Preliminary studies on the nuclear factor kappa B pathway were conducted by western blot analysis. A BEL 7402-luc subcutaneous tumor model was established for the in vivo antitumor studies of britanin. In vivo bioluminescence imaging was conducted to monitor changes in tumor size. Results: The results of the cytotoxicity analysis showed that the IC50 values for britanin in BEL 7402 and HepG2 cells were 2.702μM and 6.006μM, respectively. The results of the colony formation demonstrated that the number of cells in a colony was reduced significantly after britanin treatment. And the results of transwell migration assays showed that the migration ability of tumor cells was significantly weakened after treatment with britanin. Tumor size measurements and staining results showed that tumor size was inhibited after britanin treatment. The western blot analysis results showed the inhibition of p65 protein expression and reduced the ratio of Bcl-2/Bax after treatment. Conclusion: A series of in vitro and in vivo experiments demonstrated that britanin had good antitumor effects and provided an option for hepatocellular carcinoma treatment.


Liver Cancer ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 94-106
Author(s):  
Seung Baek Hong ◽  
Sang Hyun Choi ◽  
So Yeon Kim ◽  
Ju Hyun Shim ◽  
Seung Soo Lee ◽  
...  

<b><i>Purpose:</i></b> Microvascular invasion (MVI) is an important prognostic factor in patients with hepatocellular carcinoma (HCC). However, the reported results of magnetic resonance imaging (MRI) features for predicting MVI of HCC are variable and conflicting. Therefore, this meta-analysis aimed to identify the significant MRI features for MVI of HCC and to determine their diagnostic value. <b><i>Methods:</i></b> Original studies reporting the diagnostic performance of MRI for predicting MVI of HCC were identified in MEDLINE and EMBASE up until January 15, 2020. Study quality was assessed using QUADAS-2. A bivariate random-effects model was used to calculate the meta-analytic pooled diagnostic odds ratio (DOR) and 95% confidence interval (CI) for each MRI feature for diagnosing MVI in HCC. The meta-analytic pooled sensitivity and specificity were calculated for the significant MRI features. <b><i>Results:</i></b> Among 235 screened articles, we found 36 studies including 4,274 HCCs. Of the 15 available MRI features, 7 were significantly associated with MVI: larger tumor size (&#x3e;5 cm) (DOR = 5.2, 95% CI [3.0–9.0]), rim arterial enhancement (4.2, 95% CI [1.7–10.6]), arterial peritumoral enhancement (4.4, 95% CI [2.8–6.9]), peritumoral hypointensity on hepatobiliary phase imaging (HBP) (8.2, 95% CI [4.4–15.2]), nonsmooth tumor margin (3.2, 95% CI [2.2–4.4]), multifocality (7.1, 95% CI [2.6–19.5]), and hypointensity on T1-weighted imaging (T1WI) (4.9, 95% CI [2.5–9.6]). Both peritumoral hypointensity on HBP and multifocality showed very high meta-analytic pooled specificities for diagnosing MVI (91.1% [85.4–94.8%] and 93.3% [74.5–98.5%], respectively). <b><i>Conclusions:</i></b> Seven MRI features including larger tumor size, rim arterial enhancement, arterial peritumoral enhancement, peritumoral hypointensity on HBP, nonsmooth margin, multifocality, and hypointensity on T1WI were significant predictors for MVI of HCC. These MRI features predictive of MVI can be useful in the management of HCC.


2021 ◽  
Vol 13 ◽  
pp. 175883592098707
Author(s):  
Carolina Méndez-Blanco ◽  
Paula Fernández-Palanca ◽  
Flavia Fondevila ◽  
Javier González-Gallego ◽  
José L. Mauriz

Background: Hepatocellular carcinoma (HCC) is a highly recurrent tumor after resection and has been closely related to hypoxia. Hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) have been shown to contribute to tumor progression and therapy resistance in HCC. We evaluated the prognostic and clinicopathological significance of HIF-1α and HIF-2α in HCC patients. Methods: We systematically searched Embase, Cochrane, PubMed, Scopus and Web of Science (WOS) from inception to 1 June 2020 for studies evaluating HIF-1α and/or HIF-2α expression in HCC. Selected articles evaluate at least one factor by immunohistochemistry (IHC) in HCC patients who underwent surgical resection, and its relationship with prognosis and/or clinicopathological features. Study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CDR42020191977). We meta-analyzed the data extracted or estimated according to the Parmar method employing STATA software. We evaluated the overall effect size for the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI), as well as heterogeneity across studies with the I2 statistic and chi-square-based Q test. Moreover, we conducted subgroup analysis when heterogeneity was substantial. Publication bias was assessed by funnel plot asymmetry and Egger’s test. Results: HIF-1α overexpression was correlated with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and clinicopathological features including Barcelona Clinic Liver Cancer (BCLC), capsule infiltration, intrahepatic metastasis, lymph node metastasis, tumor–node–metastasis (TNM), tumor differentiation, tumor number, tumor size (3 cm), vascular invasion and vasculogenic mimicry. We also detected a possible correlation of HIF-1α with alpha-fetoprotein (AFP), cirrhosis, histological grade, tumor size (5 cm) and albumin after subgroup analysis. Initially, only DFS/RFS appeared to be associated with HIF-2α overexpression. Subgroup analysis denoted that HIF-2α overexpression was related to OS and capsule infiltration. Conclusions: HIF-1α and HIF-2α overexpression is related to poor OS, DFS/RFS and some clinicopathological features of HCC patients, suggesting that both factors could be useful HCC biomarkers.


Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 486
Author(s):  
Akihiro Funaoka ◽  
Kazushi Numata ◽  
Atsuya Takeda ◽  
Yusuke Saigusa ◽  
Yuichirou Tsurugai ◽  
...  

Radiotherapy is one of the available curative therapies for hepatocellular carcinoma (HCC). We investigate the use of contrast-enhanced ultrasound using Sonazoid (SCEUS) in evaluating the efficacy of radiotherapy for HCC. We enrolled 59 patients with 59 HCCs in this retrospective study. Tumor size and tumor vascularity were evaluated using SCEUS before and 1, 3, 7, 10, and 13 months after radiotherapy. The median follow-up period was 44.5 months (range: 16–82 months). Of the HCCs, 95% (56/59) had no local recurrence, while 5% (3/59) did. At 13 months after radiotherapy, in cases with no local recurrence, SCEUS showed a reduction in tumor vascularity in all cases, while tumor size reduction (>30% reduction, compared with pre-radiotherapy) was observed in 82.1% (46/56). In all three cases of local recurrence, vascularity and tumor size reduction were not observed during the follow-up period and residual HCCs were demonstrated pathologically. Compared with cases with local recurrence, tumor size reduction and reduction in tumor vascularity (p < 0.001) were significantly greater in cases with no local recurrence at 13 months after radiotherapy. SCEUS may be useful in evaluating radiotherapy efficacy for HCC.


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