Correlation between 18F-FDG PET/CT metabolic parameters and microvascular invasion before liver transplantation in patients with hepatocellular carcinoma.

BACKGROUND: Microvascular infiltration (MVI) before liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is associated with postoperative tumor recurrence and survival. MVI is mainly assessed by pathological analysis of tissue samples, which is invasive and heterogeneous. PET/computed tomography (PET/CT) with 18F-labeled fluorodeoxyglucose (18F-FDG) as a tracer has been widely used in the examination of malignant tumors. This study investigated the association between 18F-FDG PET/CT metabolic parameters and MVI before LT in HCC patients. METHODS: About 124 HCC patients who had 18F-FDG PET/CT examination before LT were included. The patients' clinicopathological features and 18F-FDG PET/CT metabolic parameters were recorded. Correlations between clinicopathological features, 18F-FDG PET/CT metabolic parameters, and MVI were analyzed. ROC curve was used to determine the optimal diagnostic cutoff value, area under the curve (AUC), sensitivity, and specificity for predictors of MVI. RESULT: In total 72 (58.06%) patients were detected with MVI among the 124 HCC patients. Univariate analysis showed that tumor size (P = 0.001), T stage (P < 0.001), maximum standardized uptake value (SUVmax) (P < 0.001), minimum standardized uptake value (SUVmin) (P = 0.031), mean standardized uptake value (SUVmean) (P = 0.001), peak standardized uptake value (SUVpeak) (P = 0.001), tumor-to-liver ratio (SUVratio) (P = 0.010), total lesion glycolysis (TLG) (P = 0.006), metabolic tumor volume (MTV) (P = 0.011) and MVI were significantly different. Multivariate logistic regression showed that tumor size (P = 0.018), T stage (P = 0.017), TLG (P = 0.023), and MTV (P = 0.015) were independent predictors of MVI. In the receiver operating characteristic curve, TLG predicted MVI with an AUC value of 0.645. MTV predicted MVI with an AUC value of 0.635. Patients with tumor size ≥5 cm, T3-4, TLG > 400.67, and MTV > 80.58 had a higher incidence of MVI. CONCLUSION: 18F-FDG PET/CT metabolic parameters correlate with MVI and may be used as a noninvasive technique to predict MVI before LT in HCC patients.

Study on high-precision three-dimensional reconstruction of pulmonary lesions and surrounding blood vessels based on CT images.

The adoption of computerized tomography (CT) technology has significantly elevated the role of pulmonary CT imaging in diagnosing and treating pulmonary diseases. However, challenges persist due to the complex relationship between lesions within pulmonary tissue and the surrounding blood vessels. These challenges involve achieving precise three-dimensional reconstruction while maintaining accurate relative positioning of these elements. To effectively address this issue, this study employs a semi-automatic precise labeling process for the target region. This procedure ensures a high level of consistency in the relative positions of lesions and the surrounding blood vessels. Additionally, a morphological gradient interpolation algorithm, combined with Gaussian filtering, is applied to facilitate high-precision three-dimensional reconstruction of both lesions and blood vessels. Furthermore, this technique enables post-reconstruction slicing at any layer, facilitating intuitive exploration of the correlation between blood vessels and lesion layers. Moreover, the study utilizes physiological knowledge to simulate real-world blood vessel intersections, determining the range of blood vessel branch angles and achieving seamless continuity at internal blood vessel branch points. The experimental results achieved a satisfactory reconstruction with an average Hausdorff distance of 1.5 mm and an average Dice coefficient of 92%, obtained by comparing the reconstructed shape with the original shape,the approach also achieves a high level of accuracy in three-dimensional reconstruction and visualization. In conclusion, this study is a valuable source of technical support for the diagnosis and treatment of pulmonary diseases and holds promising potential for widespread adoption in clinical practice.

Eosinophilia in a patient with aggressive systemic mastocytosis harboring a KIT D816V mutation: A case report.

Eosinophilia may result from three main causes: secondary (reactive), primary (clonal), and/or idiopathic. The diagnosis of idiopathic eosinophilia must be made based on excluding all reactive or clonal causes. However, some causes may be very rare so as to be misdiagnosed as idiopathic. We present the case of eosinophilia caused by aggressive systemic mastocytosis, originally recognized as idiopathic. Lymphadenopathy, dysmyelopoiesis, and hepatosplenomegaly gradually appeared and deteriorated with increasing eosinophils. This case carried KIT D816V mutation. The BCR::ABL fusion gene and the mutations in JAK2 V617F, PDGFRα, and PDGFRß in bone marrow were all negative. PHF6, PPM1D, and TET2 mutations were demonstrable. The patient was prescribed to avapritinib. The condition was effectively controlled. However, the patient discontinued medication for economic reasons 5 months later. Disease progression happened and died 10 months after diagnosis. Our study indicates that gene mutation detection at diagnosis is helpful for patient accurate diagnosis and targeted therapy of such patients.

Quantitative analysis with multiphase contrast-enhanced computed tomography to evaluate residual tumor activity of hepatocellular carcinoma after DEB-TACE.

Most hepatocellular carcinomas (HCC) treated by transcatheter arterial chemoembolization with drug-eluting beads (DEB-TACE) are characterized by coagulation necrosis; therefore, it is often difficult to distinguish enhancement in the arterial phase that would lead to false negative evaluation. This study aimed to evaluate the specificity and sensitivity of the difference value of multiphase contrast-enhanced computed tomography (CECT) in predicting residual tumor activity in HCC lesions after DEB-TACE. This retrospective diagnostic study analyzed CECT images of 73 HCC lesions in 57 patients 20 to 40 days (average 28 days) after DEB-TACE treatment at our Hospital from January to December 2019. Postoperative pathology or digital subtraction angiography images were used as references. Residual tumor activity after the first intervention was determined based on the presence of tumor staining in digital subtraction angiography or the postoperative pathological discovery of HCC tumor cells. A significant difference was observed between the active and inactive residual groups in ∆ HU difference between CT values of arterial phase and non-contrast scans (AN, P = .000), difference between CT values of venous phase and non-contrast scans (VN, P = .000), difference between CT values of delay phase and non-contrast scans (DN, P = .000), (difference between CT values of venous and arterial phase scans, P = .001), and (difference between CT values of delay and arterial phase scans, P = .005). No statistically significant difference was observed between the delayed and venous phases (difference between CT values of delay and venous phase scans, P = .361). The area under the curve (AUC) of the ROC curve showed that the diagnostic efficacies in difference in CT value of AN (AUC = 0.976), VN (AUC = 0.927), and DN (AUC = 0.924) were higher, and their cutoff values were 4.86, 12.065, 20.19 HU with their sensitivities of 93.3%, 84.4%, 77.8% and specificities of 100%, 96.4%, and 100%, respectively. difference in CT value values of AN, VN, DN, difference between CT values of venous and arterial phase scans and difference between CT values of delay and arterial phase scans can sensitively detect residual tumor activity 20-40 days after DEB-TACE. Thus, more sensitive active residual foci were detected using all 3 enhanced phases rather than only the arterial phase. Quantitative analysis of multiphase CECT can detect residual tumor activity in an early and noninvasive manner, which can provide time for patients to receive early follow-up treatment.

A new classification and regression tree algorithm: Improved diagnostic sensitivity for HCC ≤ 3.0 cm using gadoxetate disodium-enhanced MRI.

PURPOSE: To develop and validate an effective algorithm, based on classification and regression tree (CART) analysis and LI-RADS features, for diagnosing HCC ≤ 3.0 cm with gadoxetate disodium­enhanced MRI (Gd-EOB-MRI). METHOD: We retrospectively included 299 and 90 high-risk patients with hepatic lesions ≤ 3.0 cm that underwent Gd-EOB-MRI from January 2018 to February 2021 in institution 1 (development cohort) and institution 2 (validation cohort), respectively. Through binary and multivariate regression analyses of LI-RADS features in the development cohort, we developed an algorithm using CART analysis, which comprised the targeted appearance and independently significant imaging features. On per-lesion basis, we compared the diagnostic performances of our algorithm, two previously reported CART algorithms, and LI-RADS LR-5 in development and validation cohorts. RESULTS: Our CART algorithm, presenting as a decision tree, included targetoid appearance, HBP hypointensity, nonrim arterial phase hyperenhancement (APHE), and transitional phase hypointensity plus mild-moderate T2 hyperintensity. For definite HCC diagnosis, the overall sensitivity of our algorithm (development cohort 93.2%, validation cohort 92.5%; P < 0.006) was significantly higher than those of Jiang's algorithm modified LR-5 (defined as targetoid appearance, nonperipheral washout, restricted diffusion, and nonrim APHE) and LI-RADS LR-5, with the comparable specificity (development cohort: 84.3%, validation cohort: 86.7%; P ≥ 0.006). Our algorithm, providing the highest balanced accuracy (development cohort: 91.2%, validation cohort: 91.6%), outperformed other criteria for identifying HCCs from non-HCC lesions. CONCLUSIONS: In high-risk patients, our CART algorithm developed with LI-RADS features showed promise for the early diagnosis of HCC ≤ 3.0 cm with Gd-EOB-MRI.

Imaging features of retinal hemangioblastoma: A case report.

BACKGROUND: Hemangioblastoma typically occurs in the cerebellum, spinal cord, and central nervous system. However, in rare cases, it could occur in the retina or optic nerve. The prevalence of retinal hemangioblastoma is 1 in 73080, and it occurs either alone or as the manifestation of von Hippel Lindau (VHL) disease. Here, we reported a rare case with the imaging features of retinal hemangioblastoma without VHL syndrome, along with the relevant literature review. CASE SUMMARY: A 53-year-old man had progressive swelling, pain and blurred vision in the left eye without obvious inducement for 15 d. Ultrasonography revealed a possible optic nerve head melanoma. Computed tomography (CT) showed punctate calcification on the posterior wall of the left eye ring and small patchy soft tissue density in the posterior part of the eyeball. Magnetic resonance imaging showed slightly hyperintense signal on T1-weighted images and slightly hypointense-to-isointense signal on T2-weighted images at the medial and posterior edges of the left eyeball, a significant enhancement was observed in the contrast-enhanced scans. Positron emission tomography/CT fusion images showed that the glucose metabolism of the lesion was normal. Pathology was consistent with hemangioblastoma. CONCLUSION: Early identification of retinal hemangioblastoma based on imaging features is of great value for its personalized treatment.

Current status and prospect of PET-related imaging radiomics in lung cancer.

Lung cancer is highly aggressive, which has a high mortality rate. Major types encompass lung adenocarcinoma, lung squamous cell carcinoma, lung adenosquamous carcinoma, small cell carcinoma, and large cell carcinoma. Lung adenocarcinoma and lung squamous cell carcinoma together account for more than 80% of cases. Diverse subtypes demand distinct treatment approaches. The application of precision medicine necessitates prompt and accurate evaluation of treatment effectiveness, contributing to the improvement of treatment strategies and outcomes. Medical imaging is crucial in the diagnosis and management of lung cancer, with techniques such as fluoroscopy, computed radiography (CR), digital radiography (DR), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)/CT, and PET/MRI being essential tools. The surge of radiomics in recent times offers fresh promise for cancer diagnosis and treatment. In particular, PET/CT and PET/MRI radiomics, extensively studied in lung cancer research, have made advancements in diagnosing the disease, evaluating metastasis, predicting molecular subtypes, and forecasting patient prognosis. While conventional imaging methods continue to play a primary role in diagnosis and assessment, PET/CT and PET/MRI radiomics simultaneously provide detailed morphological and functional information. This has significant clinical potential value, offering advantages for lung cancer diagnosis and treatment. Hence, this manuscript provides a review of the latest developments in PET-related radiomics for lung cancer.

Combination treatment of radiofrequency ablation and peptide neoantigen vaccination: Promising modality for future cancer immunotherapy.

Background: The safety and immunogenicity of a personalized neoantigen-based peptide vaccine, iNeo-Vac-P01, was reported previously in patients with a variety of cancer types. The current study investigated the synergistic effects of radiofrequency ablation (RFA) and neoantigen vaccination in cancer patients and tumor-bearing mice. Methods: Twenty-eight cancer patients were enrolled in this study, including 10 patients who had received RFA treatment within 6 months before vaccination (Cohort 1), and 18 patients who had not (Cohort 2). Individualized neoantigen peptide vaccines were designed, manufactured, and subcutaneously administrated with GM-CSF as an adjuvant for all patients. Mouse models were employed to validate the synergistic efficacy of combination treatment of RFA and neoantigen vaccination. Results: Longer median progression free survival (mPFS) and median overall survival (mOS) were observed in patients in Cohort 1 compared to patients in Cohort 2 (4.42 and 20.18 months vs. 2.82 and 10.94 months). The results of ex vivo IFN-γ ELISpot assay showed that patients in Cohort 1 had stronger neoantigen-specific immune responses at baseline and post vaccination. Mice receiving combination treatment of RFA and neoantigen vaccines displayed higher antitumor immune responses than mice receiving single modality. The combination of PD-1 blockage with RFA and neoantigen vaccines further enhanced the antitumor response in mice. Conclusion: Neoantigen vaccination after local RFA treatment could improve the clinical and immune response among patients of different cancer types. The synergistic antitumor potentials of these two modalities were also validated in mice, and might be further enhanced by immune checkpoint inhibition. The mechanisms of their synergies require further investigation. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT03662815.

A Pan-cancer Clinical Study of Personalized Neoantigen Vaccine Monotherapy in Treating Patients with Various Types of Advanced Solid Tumors.

PURPOSE: Because of their high tumor specificity and immunogenicity, neoantigens have been considered as ultimate targets for cancer immunotherapy. Neoantigen-based vaccines have demonstrated promising efficacy for several cancer types. To further investigate the antitumor potentials for other types of solid tumors, we designed a peptide-based neoantigen vaccine, iNeo-Vac-P01, and conducted a single-arm, open-labeled, investigator-initiated clinical trial (NCT03662815). PATIENTS AND METHODS: Personalized neoantigen vaccines were designed and manufactured according to our bioinformatics analysis results from the whole-exome sequencing of tumor and peripheral blood cell DNAs. Patients were scheduled to be vaccinated subcutaneously with adjuvant on days 1, 4, 8, 15, and 22 (prime phase), and days 78 and 162 (boost phase). Additional immunizations were administrated every 2-3 months as per patient's potential benefit. The safety and efficacy were assessed through adverse events (AE), progression-free survival (PFS), overall survival (OS), and other parameters. RESULTS: Of the 22 patients enrolled with advanced malignancies, 20 had no or mild AEs, while 2 had grade 3 or 4 acute allergic reactions only after their sixth boost vaccination. The disease control rate was 71.4%. The median PFS was 4.6 months, whereas the median OS was not reached (12-month OS = 55.1%). Around 80% of individual peptides or peptide pools elicited measurable specific immune response. In addition, our findings revealed several potential biomarkers for the prediction of better response. CONCLUSIONS: iNeo-Vac-P01 as monotherapy is feasible and safe for patients with advanced solid tumors. It could elicit T-cell-mediated immune response targeting tumor neoantigens, and might have promising antitumor efficacy.See related commentary by Filderman and Storkus, p. 4429.

Effects of transection of cervical sympathetic trunk on cognitive function of traumatic brain injury rats.

Objective: To observe the effects of transection of cervical sympathetic trunk (TCST) on the cognitive function of traumatic brain injury (TBI) rats and the potential mechanisms. Methods: A total of 288 adult male SD rats were divided into 3 groups using a random number table: TBI group (n=96), TBI + TCST group (n=96) and Sham group (n=96). The water maze test was performed before TBI (T0) and at day 1 (T1), day 2 (T2), day 3 (T3), 1 week (T4), 2 weeks (T5), 6 weeks (T6) and 12 weeks (T7) after TBI. The levels of α1-adrenergic receptors (α1-ARs), α2-adrenergic receptors (α2-ARs), toll-like receptor 4 (TLR-4) and P38 in hippocampi were detected by real-time PCR. Hippocampal P38 expression was assayed by Western blot. The expressions of interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and brain-derived neurotrophic factor (BDNF) were examined by immunohistochemistry. Noradrenaline (NE) expression in plasma was evaluated by ELISA. The respiratory control ratio (RCR) of brain mitochondria was detected using a Clark oxygen electrode. Results: TCST effectively improved the cognitive function of TBI rats. TCST significantly inhibited sympathetic activity in the rats and effectively inhibited inflammatory responses. The expression of BDNF at T1-T6 in TBI+TCST group was higher than that in TBI group (P<0.05). Furthermore, P38 expression was inhibited more effectively in TBI+TCST group (P<0.05), than in TBI group (P<0.05), and the RCR of the brain was significantly higher in TBI+TCST group than in TBI group (P<0.05). Conclusions: TCST can enhance cognitive function in TBI rats by inhibiting sympathetic activity, reducing inflammatory responses and brain edema, upregulating BDNF and improving brain mitochondrial function.