Regorafenib for patients with progression of advanced hepatocellular carcinoma after treatment with atezolizumab plus bevacizumab: a case series.

Background: Immunotherapy has reshaped the systemic treatment of hepatocellular carcinoma (HCC), with atezolizumab plus bevacizumab (TA) regimen and regorafenib being the first-line and second-line treatment options for advanced HCC, respectively. However, the efficacy of using the second-line therapeutic agent regorafenib in patients with HCC that has progressed after TA regimen treatment is unknown, and there is a lack of supporting clinical data. The purpose of this case series was to evaluate the clinical efficacy of the second-line therapeutic agent regorafenib in patients with advanced HCC who progressed after treatment with a first-line TA regimen. Case Description: This case series included five patients with intermediate to advanced HCC treated with regorafenib after progression on a TA regimen. We retrospectively report the clinical data, clinical outcomes, and adverse events of these five patients. According to modified Response Evaluation Criteria in Solid Tumors (mRECIST), one patient achieved partial response (PR), three patients achieved stable disease (SD), and one patient experienced progressive disease (PD); the disease control rate (DCR) reached 80%, and the objective response rate (ORR) reached 20%. Conclusions: In patients with intermediate to advanced HCC who experience disease progression after TA therapy, second-line treatment with regorafenib may be effective in delaying progression and may be associated with better disease control. However, these findings need to be further confirmed in prospective studies with larger cohorts.

Immunotherapy combined with cranial radiotherapy for driver-negative non-small-cell lung cancer brain metastases: a retrospective study.

Background: This study assesses immune checkpoint inhibitors' efficacy for non-small-cell lung cancer (NSCLC) with brain metastases (BM) and explores the role of cranial radiation therapy (CRT) in the immunotherapy era. Methods: The retrospective analysis screened NSCLC patients with BMs from July 2018 to December 2021. Treatment involved chemotherapy combined with immune checkpoint inhibitors as the first-line, with patients divided into CRT and non-CRT groups. Overall survival (OS), progression-free survival and intracranial progression-free survival were calculated and compared. Results: Among 113 patients, 74 who received CRT had significantly better median OS (not reached vs 15.31 months), particularly among those with one to three BMs. Factors correlating with better OS included CRT, PD-L1 expression and diagnosis-specific graded prognostic assessment scores. Conclusion: Integrating CRT with anti-PD-1 therapy notably enhanced long-term survival in NSCLC patients with BMs.

[Box: see text].

Nanomaterials modulate tumor-associated macrophages for the treatment of digestive system tumors.

The treatment of digestive system tumors presents challenges, particularly in immunotherapy, owing to the advanced immune tolerance of the digestive system. Nanomaterials have emerged as a promising approach for addressing these challenges. They provide targeted drug delivery, enhanced permeability, high bioavailability, and low toxicity. Additionally, nanomaterials target immunosuppressive cells and reshape the tumor immune microenvironment (TIME). Among the various cells in the TIME, tumor-associated macrophages (TAMs) are the most abundant and play a crucial role in tumor progression. Therefore, investigating the modulation of TAMs by nanomaterials for the treatment of digestive system tumors is of great significance. Here, we present a comprehensive review of the utilization of nanomaterials to modulate TAMs for the treatment of gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic cancer. We also investigated the underlying mechanisms by which nanomaterials modulate TAMs to treat tumors in the digestive system. Furthermore, this review summarizes the role of macrophage-derived nanomaterials in the treatment of digestive system tumors. Overall, this research offers valuable insights into the development of nanomaterials tailored for the treatment of digestive system tumors.

Development and validation of a nomogram for radiation-induced hepatic toxicity after intensity modulated radiotherapy for hepatocellular carcinoma: a retrospective study.

OBJECTIVE: This study aimed to construct a nomogram to predict radiation-induced hepatic toxicity in patients with hepatocellular carcinoma treated with intensity-modulated radiotherapy. METHODS: This study reviewed the clinical characteristics and dose-volume parameters of 196 patients with hepatocellular carcinoma. Radiation-induced hepatic toxicity was defined as progression of the Child-Pugh score caused by intensity-modulated radiotherapy. Factors relevant to radiation-induced hepatic toxicity were selected using receiver operating characteristic and univariate logistic analysis. A risk assessment model was developed, and its discrimination was validated. RESULTS: Eighty-eight (44.90%) and 28 (14.29%) patients had radiation-induced hepatic toxicity ≥ 1 (Child-Pugh ≥ 1) and radiation-induced hepatic toxicity ≥ 2 (Child-Pugh ≥ 2). Pre-treatment Child-Pugh, body mass index and dose-volume parameters were correlated with radiation-induced hepatic toxicity ≥ 1 using univariate logistic analysis. V15 had the best predictive effectiveness among the dose-volume parameters in both the training (area under the curve: 0.763, 95% confidence interval: 0.683-0.842, P < 0.001) and validation cohorts (area under the curve: 0.759, 95% confidence interval: 0.635-0.883, P < 0.001). The area under the curve values of the model that was constructed by pre-treatment Child-Pugh, body mass index and V15 for radiation-induced hepatic toxicity ≥1 were 0.799 (95% confidence interval: 0.719-0.878, P < 0.001) and 0.775 (95% confidence interval: 0.657-0.894, P < 0.001) in the training and validation cohorts, respectively. Patients with a body mass index ≤ 20.425, Barcelona clinic liver cancer = C, Hepatitis B Virus-positive, Eastern Cooperative Oncology Group = 1-2 and hepatic fibrosis require lower V15 dose limits. CONCLUSIONS: Risk assessment model constructed from Pre-treatment Child-Pugh, V15 and body mass index can guide individualized patient selection of toxicity minimization strategies.

Application of radiomics-based multiomics combinations in the tumor microenvironment and cancer prognosis.

The advent of immunotherapy, a groundbreaking advancement in cancer treatment, has given rise to the prominence of the tumor microenvironment (TME) as a critical area of research. The clinical implications of an improved understanding of the TME are significant and far-reaching. Radiomics has been increasingly utilized in the comprehensive assessment of the TME and cancer prognosis. Similarly, the advancement of pathomics, which is based on pathological images, can offer additional insights into the panoramic view and microscopic information of tumors. The combination of pathomics and radiomics has revolutionized the concept of a "digital biopsy". As genomics and transcriptomics continue to evolve, integrating radiomics with genomic and transcriptomic datasets can offer further insights into tumor and microenvironment heterogeneity and establish correlations with biological significance. Therefore, the synergistic analysis of digital image features (radiomics, pathomics) and genetic phenotypes (genomics) can comprehensively decode and characterize the heterogeneity of the TME as well as predict cancer prognosis. This review presents a comprehensive summary of the research on important radiomics biomarkers for predicting the TME, emphasizing the interplay between radiomics, genomics, transcriptomics, and pathomics, as well as the application of multiomics in decoding the TME and predicting cancer prognosis. Finally, we discuss the challenges and opportunities in multiomics research. In conclusion, this review highlights the crucial role of radiomics and multiomics associations in the assessment of the TME and cancer prognosis. The combined analysis of radiomics, pathomics, genomics, and transcriptomics is a promising research direction with substantial research significance and value for comprehensive TME evaluation and cancer prognosis assessment.

A self-adjusting ant colony clustering algorithm for ECG arrhythmia classification based on a correction mechanism.

BACKGROUND AND OBJECTIVE: As a representative type of cardiovascular disease, persistent arrhythmias can often become life-threatening. In recent years, machine learning-based ECG arrhythmia classification aided methods have been effective in assisting physicians with their diagnosis, but these methods have problems such as complex model structures, poor feature perception ability, and low classification accuracy. METHODS: In this paper, a self-adjusting ant colony clustering algorithm for ECG arrhythmia classification based on a correction mechanism is proposed. This method does not distinguish between subjects when establishing the dataset in order to reduce the effect of differences in ECG signal features between individuals, thus improving the robustness of the model. When the classification is achieved, a correction mechanism is introduced to correct outliers caused by the accumulation of errors in the classification process in order to improve the classification accuracy of the model. According to the principle that the flow rate of gas can be increased under the convergence channel, a dynamically updated pheromone volatilization coefficient ρ, namely the increased flow rate ρ, is introduced to help the model converge more stably and faster. As the ants move, the next transfer target is selected by a truly self-adjusting transfer method, and the transfer probability is dynamically adjusted according to the pheromone concentration and the path distance. RESULTS: Based on the MIT-BIH arrhythmia dataset, the new algorithm achieved classification of five heart rhythm types, with an overall accuracy of 99.00%. Compared to other experimental models, the classification accuracy of the proposed method represents a 0.2% to 16.6% improvement, and compared to other current studies, the classification accuracy of the proposed method is 0.65% to 7.5% better. CONCLUSIONS: This paper addresses the shortcomings of ECG arrhythmia classification methods based on feature engineering, traditional machine learning and deep learning, and presents a self-adjusting ant colony clustering algorithm for ECG arrhythmia classification based on a correction mechanism. Experiments demonstrate the superiority of the proposed method compared to basic models as well as those with improved partial structures. Furthermore, the proposed method achieves very high classification accuracy with a simple structure and fewer iterations than other current methods.

Prevalence and prognostic impact of hepatopulmonary syndrome in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization: a prospective cohort study.

BACKGROUND: To determine the prevalence and prognostic impact of hepatopulmonary syndrome (HPS) in patients with unresectable hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). METHODS: Fifty-four patients with unresectable HCC undergoing TACE between December 2014 and December 2015 were prospectively screened for HPS and were followed up for a maximum of 2 years or until the end of this prospective study. RESULTS: Nineteen of the 54 (35.2%) patients were considered to have HPS, including one (5.3%) with severe HPS, nine (47.4%) with moderate HPS, and nine (47.4%) with mild HPS. The median overall survival (OS) was 10.1 (95% confidence interval [CI], 3.9-16.3) months for patients with HPS and 15.1 (95% CI, 7.3-22.9) months for patients without HPS, which is not a significant difference ( P  = 0.100). The median progression-free survival was also not significantly different between patients with and without HPS (5.2 [95% CI, 0-12.8] vs. 8.4 [95% CI, 3.6-13.1] months; P  = 0.537). In the multivariable Cox regression analyses, carbon monoxide diffusing capacity (hazard ratio [HR] = 1.033 [95% CI, 1.003-1.064]; P  = 0.028) and Child-Pugh class (HR = 1.815 [95% CI, 1.011-3.260]; P  = 0.046) were identified to be the independent prognostic factors of OS. CONCLUSION: Mild or moderate HPS is common in patients with unresectable HCC undergoing TACE, but it does not seem to have a significant prognostic impact.

Spiral Suture of the Lower Uterine Segment with Temporary Aortic Balloon Occlusion in Morbidly Adherent Placenta Previa Cases.

Purpose: We aimed to investigate the combined effect of spiral suture of the lower uterine segment with intraoperative aortic balloon occlusion in morbidly adherent placenta previa cases. Patient and Methods: This retrospective, single-center study involved patients from 2017 to 2020. The study considered 68 cases of morbidly adherent placenta previa cases from medical records retrospectively with age ranging from 23 to 42 years. Bilateral uterine artery embolization was performed, to control excessive bleeding. Perioperative blood loss, hysterectomy rate, amount of blood transfusion, balloon occlusion time, fetal and maternal radiation dose, and postpartum complications were assessed. Results: A total of 68 patients underwent surgery. Hysterectomy was performed in three patients and uterine artery embolization in 21 patients. Of 53 patients who required blood transfusions, the amount of packed red blood cells given was 800 mL and the amount of plasma given was 400 mL. Median abdominal aortic balloon occlusion time was 17 minutes. Fetal and maternal radiation doses were 5 mGy and 12 mGy, respectively. One patient experienced surgery-related complications, a bladder injury. No major catheterization-related and postpartum complications were observed. Conclusion: Fertility-sparing surgery for women with morbidly adherent placenta could include abdominal aortic balloon occlusion and spiral suture of lower uterine segment.

Time Series Forecasting of Motor Bearing Vibration Based on Informer.

Electric energy, as an economical and clean energy, plays a significant role in the development of science and technology and the economy. The motor is the core equipment of the power station; therefore, monitoring the motor vibration and predicting time series of the bearing vibration can effectively avoid hazards such as bearing heating and reduce energy consumption. Time series forecasting methods of motor bearing vibration based on sliding window forecasting, such as CNN, LSTM, etc., have the problem of error accumulation, and the longer the time-series forecasting, the larger the error. In order to solve the problem of error accumulation caused by the conventional methods of time series forecasting of motor bearing vibration, this paper innovatively introduces Informer into time series forecasting of motor bearing vibration. Based on Transformer, Informer introduces ProbSparse self-attention and self-attention distilling, and applies random search to optimize the model parameters to reduce the error accumulation in forecasting, achieve the optimization of time and space complexity and improve the model forecasting. Comparing the forecasting results of Informer and those of other forecasting models in three publicly available datasets, it is verified that Informer has excellent performance in time series forecasting of motor bearing vibration and the forecasting results reach 10-2∼10-6.

Systemic Therapy for Hepatocellular Carcinoma: Chinese Consensus-Based Interdisciplinary Expert Statements.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and causes many cancer-related deaths worldwide; in China, it is the second most prevalent cause of cancer deaths. Most patients are diagnosed clinically with advanced stage disease. Summary: For more than a decade, sorafenib, a small-molecular-weight tyrosine kinase inhibitor (SMW-TKI) was the only molecular targeted drug available with a survival benefit for the treatment of advanced HCC. With the development of novel TKIs and immune checkpoint inhibitors for advanced HCC, the management of patients has been greatly improved. However, though angiogenic-based targeted therapy remains the backbone for the systemic treatment of HCC, to date, no Chinese guidelines for novel molecular targeted therapies to treat advanced HCC have been established. Our interdisciplinary panel on the treatment of advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, pathologists, orthopedic surgeons, traditional Chinese medicine physicians, and interventional radiologists has reviewed the literature in order to develop updated treatment regimens. Key Messages: Panel consensus statements for the appropriate use of new molecular -targeted drugs including doses, combination therapies, adverse reaction management as well as efficacy evaluation, and predictions for treatment of advanced HCC with evidence levels based on published data are presented, thereby providing an overview of molecular targeted therapies for healthcare professionals.

TACE with dicycloplatin in patients with unresectable hepatocellular carcinoma: a multicenter randomized phase II trial.

OBJECTIVES: To investigate the efficacy and safety of dicycloplatin as chemotherapeutic regimen in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). METHODS: In this randomized, open-label, phase II trial, patients with unresectable HCC who were TACE treatment-naïve or experienced recurrence after surgical resection or ablation were enrolled at 7 centers in China from March 2019 to November 2019. Participants were randomly assigned (1:1:1) to receive TACE with chemotherapeutic regimen of dicycloplatin alone (group A1), dicycloplatin plus epirubicin (group A2), or epirubicin alone (group B). The primary endpoint was objective response rate (ORR). The secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and safety. RESULTS: The ORR at 6 months in group A1 (n = 22) was significantly better than that in group B (p = 0.093; 90% confidence interval [CI], 1.03-9.45). The DCR in group A1 was significantly higher than that in group B (p = 0.045; 90% CI, 1.29-12.88). There was no significant difference in DOR among the groups (p = 0.271). The median PFS were 6.00 and 3.05 months in groups A2 (n = 25) and B (n = 24), respectively (p = 0.061). Grade 3 or worse adverse events were similar among groups in the safety population (p = 0.173). CONCLUSION: TACE with dicycloplatin was comparably safe and well tolerable as epirubicin alone in patients with unresectable HCC. Compared with epirubicin alone, significant improvement in ORR and DCR when dicycloplatin was applied, as well as prolonged PFS when dicycloplatin plus epirubicin was applied, was generated. KEY POINTS: • To our knowledge, this is the first multicenter randomized trial to assess the efficacy and safety of TACE with dicycloplatin in patients with unresectable HCC. • This phase II trial showed that TACE with dicycloplatin alone or plus epirubicin was comparably safe and well tolerable as epirubicin alone. • Significant improvements in ORR, DCR when dicycloplatin was applied, and prolonged PFS when dicycloplatin plus epirubicin was applied were recorded compared with epirubicin alone.

Expert consensus on thermal ablation therapy of pulmonary subsolid nodules (2021 Edition).

The Expert Consensus reviews current literatures and provides clinical practice guidelines for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The main contents include the following: (1) clinical evaluation of GGN; (2) procedures, indications, contraindications, outcomes evaluation, and related complications of thermal ablation for GGN; and (3) future development directions.

Enzyme-induced morphological transformation of drug carriers: Implications for cytotoxicity and the retention time of antitumor agents.

Nanocarriers have been widely employed to deliver chemotherapeutic drugs for cancer treatment. However, the insufficient accumulation of nanoparticles in tumors is an important reason for the poor efficacy of nanodrugs. In this study, a novel drug delivery system with a self-assembled amphiphilic peptide was designed to respond specifically to alkaline phosphatase (ALP), a protease overexpressed in cancer cells. The amphiphilic peptide self-assembled into spherical and fibrous nanostructures, and it easily assembled into spherical drug-loaded peptide nanoparticles after loading of a hydrophobic chemotherapeutic drug. The cytotoxicity of the drug carriers was enhanced against tumor cells over time. These spherical nanoparticles transformed into nanofibers under the induction of ALP, leading to efficient release of the encapsulated drug. This drug delivery strategy relying on responsiveness to an enzyme present in the tumor microenvironment can enhance local drug accumulation at the tumor site. The results of live animal imaging showed that the residence time of the morphologically transformable drug-loaded peptide nanoparticles at the tumor site was prolonged in vivo, confirming their potential use in antitumor therapy. These findings can contribute to a better understanding of the influence of drug carrier morphology on intracellular retention.

[Expert Consensus for Thermal Ablation of Pulmonary Subsolid Nodules (2021 Edition)].

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
.

Percutaneous stent placement for malignant hilar biliary obstruction: side-by-side versus stent-in-stent technique.

BACKGROUND: Currently, side-by-side (SBS) and stent-in-stent (SIS) are the two main techniques for stent deployment to treat hilar biliary obstructions. Previous studies comparing these two techniques are very limited, and thus, no consensus has been reached on which technique is better. The purpose of this study is to compare the clinical efficacy and safety of SBS and SIS deployment via a percutaneous approach for malignant hilar biliary obstruction. METHODS: From July 2012 to April 2019, 65 patients with malignant hilar biliary obstruction who underwent bilateral stenting using either the SBS or SIS techniques were included in this study. Among them, 27 patients underwent SIS stent insertion (SIS group), and the remaining 38 patients underwent SBS stent insertion (SBS group). Technical success, improvement of jaundice, complications, duration of stent patency, and overall survival were evaluated. RESULTS: Technical success was achieved in all patients in the two groups. The serum bilirubin level decreased more rapidly 1 week after the procedures in the SBS group than in the SIS group (P = 0.02). Although the total complication rate did not differ between the two groups, cholangitis was found to be more frequent in the SIS group (P = 0.04). The median stent patency was significantly longer in the SBS group (149 days) than in the SIS group (75 days; P = 0.02). The median overall survival did not significantly differ between the two groups (SBS vs. SIS, 155 days vs. 143 days; P > 0.05). CONCLUSIONS: Percutaneous transhepatic bilateral stenting using either the SBS or SIS technique is safe and effective in the management of malignant hilar biliary obstruction. However, SBS offers a quicker improvement of jaundice, a lower incidence of cholangitis after the procedure, and a longer stent patency period than SIS.

Transarterial chemoembolization with medium-sized doxorubicin-eluting Callisphere is safe and effective for patients with hepatocellular carcinoma.

The study aimed to compare the tumor response to and complications of doxorubicin-eluting CalliSphere bead-transarterial chemoembolization (DEB-TACE) using small- and medium-sized beads in patients with hepatocellular carcinoma (HCC) who underwent multiple rounds of oncology therapies. Sixty patients with intermediate stage HCC who had previously received multiple oncology therapies underwent DEB-TACE with CalliSpheres of 100-300 µm (small bead group, n = 34) or 300-500 µm (medium bead group, n = 26) in diameter between October 2016 and December 2018. Adverse events and the response rate of the index tumor based on the modified Response Evaluation Criteria in Solid Tumors at 3 months post-TACE were compared between the groups. The rates of complete response, partial response, stable disease, and progressive disease were 35.4%, 29.4%, 17.6%, and 17.6%, respectively, for the small bead group and 33.1%, 23.1%, 20.8%, and 23.0%, respectively, for the medium bead group, showing no significant between-group differences (P > 0.05). Common Terminology Criteria for Adverse Events version 4.0 grade 3/4 adverse events were reported in 8 patients in the small bead group and in no patients in the medium bead group, showing a significant group difference (P < 0.01). Major complications included 8 events of ischemic hepatitis, 2 of biloma, and 2 of severe liver abscess. DEB-TACE using CalliSpheres of 300-500 µm was associated with a comparable rate of tumor response but lower rate of complications compared with that using CalliSpheres of 100-300 µm for HCC treatment in patients who had already undergone multiple rounds of oncology therapies.

Hydrogen-bond-mediated structural variation of metal guanidinium formate hybrid perovskites under pressure.

The hybrid perovskites are coordination frameworks with the same topology as the inorganic perovskites, but with properties driven by different chemistry, including host-framework hydrogen bonding. Like the inorganic perovskites, these materials exhibit many different phases, including structures with potentially exploitable functionality. However, their phase transformations under pressure are more complex and less well understood. We have studied the structures of manganese and cobalt guanidinium formate under pressure using single-crystal X-ray and powder neutron diffraction. Under pressure, these materials transform to a rhombohedral phase isostructural to cadmium guanidinium formate. This transformation accommodates the reduced cell volume while preserving the perovskite topology of the framework. Using density-functional theory calculations, we show that this behaviour is a consequence of the hydrogen-bonded network of guanidinium ions, which act as struts protecting the metal formate framework against compression within their plane. Our results demonstrate more generally that identifying suitable host-guest hydrogen-bonding geometries may provide a route to engineering hybrid perovskite phases with desirable crystal structures. This article is part of the theme issue 'Mineralomimesis: natural and synthetic frameworks in science and technology'.

Comparison of 10 prognostic staging systems in patients with advanced hepatocellular carcinoma.

PURPOSE: To compare the performance of 10 currently staging systems (TNM, Okuda, GETCH, CLIP, CUPI, JIS, CIS, MELD, mJIS, mCLIP) for predicting survival in advanced hepatocellular carcinoma (HCC) patients. METHODS: A total of 133 consecutive advanced HCC patients between January 2014 and December 2014 were enrolled in the study. The Kaplan-Meier method compared by the log-rank test was used to estimate the survival distribution. Ranking of staging systems was done by using the concordance index (c-index) to compare the discriminatory capacity. The area under the curve (AUC) was performed to assess the mortality prediction. RESULTS: The median survival of all 133 patients was 7.5 months. The survival rates at 6, 12, 18 and 24 months were 56%, 30%, 19% and 15%, respectively. CIS and CUPI systems had better performances in survival distribution. CIS, TNM and CLIP systems were the top three ranking staging systems. CIS had the best mortality prediction at 6, 18 and 24 months and CLIP had the best mortality prediction at 12 months. CONCLUSIONS: The CIS system was the most informative staging system for predicting survival in advanced HCC patients with mainly hepatitis B virus etiology.