Relaxin combined with transarterial chemoembolization achieved synergistic effects and inhibited liver cancer metastasis in a rabbit VX2 model.

OBJECTIVE: To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE). MATERIALS AND METHODS: HCCLM3 and Huh-7 cells were adopted to evaluate the effect of tumor proliferation, migration, and invasion after RLX administration in vitro. The rabbit VX2 model was used to evaluate the biosafety, doxorubicin penetration, local tumor response, tumor metastasis, and survival benefit of RLX combined with TACE treatment. RESULTS: RLX did not affect the proliferation, migration, or invasion of HCCLM3 and Huh-7 cells, and the expression of E-cadherin and HIF-1α also remained unchanged while the MMP-9 protein was upregulated in vitro. In the rabbit VX2 model, compared to the normal saline group (NS), RLX group (RLX) and TACE mono-therapy group (TACE), the group that received TACE combined with RLX (TACE + RLX) showed an improved local tumor response and survival benefit. Furthermore, TACE combined with RLX was found to reduce tumor metastasis. This combination therapy reduced the fibrotic extracellular matrix in the tumor microenvironment, allowing for better penetration of doxorubicin, improved infiltration of CD8+ T cells and affected the secretion of cytokines. Additionally, RLX combined with TACE was able to decrease the expression of HIF-1α and PD-L1. The biosafety of TACE combined with RLX was also confirmed. CONCLUSION: RLX synergized with TACE by mitigating the fibrotic extracellular matrix and tumor hypoxic microenvironment, improving the therapeutic effect and inhibiting metastasis during the treatment of liver cancer.

A scoring system for stratifying the risk of postoperative bone metastases in colorectal cancer.

BACKGROUND: Surveillance recommendations for postoperative high-risk colorectal bone metastases patients remain in a gray area of guidelines. We aimed to develop a risk stratification system to select ideal candidates for follow-up of colorectal bone metastases status. METHODS: Postoperative colorectal cancer patients were included to develop a risk-scoring system to predict bone metastases. Risk scores were calculated based on the predictive factors for bone metastases, which were identified using the Cox proportional hazard regression model. Kaplan-Meier curves visualize the differences between risk groups. RESULTS: Eight risk factors (age, lymph node metastasis, pathologic tumor deposit, KRAS mutation status, suspicious retroperitoneal lymph node metastasis, lung metastasis status, largest thickness of colorectal cancer lesion, largest short diameter of lymph node) were predictors of colorectal bone metastases and incorporated into the risk scoring system, and the patients were categorized into 2 risk groups. In the low-risk group, the 1, 3, and 5-year colorectal bone metastases rates were 2.4%, 4.6%, and 3.7%, respectively, whereas in the high-risk group, the 1, 3, and 5-year colorectal bone metastases rates were 15.6%, 29.9%, and 44.4%, respectively. The risk scoring system exhibited a C-index of 0.706, 0.795, and 0.841 in 1, 3, and 5 years, respectively. The Kaplan-Meier curve demonstrates that the incidence of colorectal bone metastases was higher in the high-risk group than in the low-risk group (50.5% vs 11.4%, P < .001). CONCLUSION: This risk-scoring system may be valuable in predicting colorectal bone metastases in colorectal cancer patients, and we suggest that colorectal bone metastases status surveillance be added in the high-risk group.

Drug-eluting beads transcatheter arterial chemoembolization combined with systemic therapy versus systemic therapy alone as first-line treatment for unresectable colorectal liver metastases.

Purpose: The purpose of this retrospective study was to compare the therapeutic efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with systemic therapy to systemic therapy alone as first-line treatment for unresectable patients with colorectal liver metastases (CRLM). Methods: From December 2017 to December 2022, patients with unresectable CRLM who received systemic therapy with or without DEB-TACE as first-line treatment were included in the study. The primary endpoint was progression-free survival (PFS). Secondary endpoints were tumor response, conversion rate and adverse events. Results: Ninety-eight patients were enrolled in this study, including 46 patients who received systemic therapy combined with DEB-TACE (DEB-TACE group) and 52 patients who received systemic therapy alone (control group). The median PFS was elevated in the DEB-TACE group compared with the control group (12.1 months vs 8.4 months, p = 0.008). The disease control rate was increased in the DEB-TACE group compared with the control group (87.0% vs 67.3%, p = 0.022). Overall response rates (39.1% vs 25.0%; p = 0.133) and conversion rate to liver resection (33.8% vs 25.0%; p = 0.290) were no different between the two groups. The multivariate analysis showed that treatment options, size of liver metastasis, number of liver metastasis, synchronous metastases, and extrahepatic metastases were independent prognostic factor of PFS. Further subgroup analyses illustrated that PFS was beneficial with the DEB-TACE group in patients with age ≥ 60, male, left colon, synchronous metastases, bilobar, number of liver metastasis > 5, extrahepatic metastases, non-extrahepatic metastases, CEA level < 5 (ng/ml), and KRAS wild-type. No grade 4 or 5 toxicities related to DEB-TACE procedures were observed. Conclusion: In patients with unresectable CRLM, systemic chemotherapy with DEB-TACE as first-line treatment may improve progression-free survival and disease control rate outcomes over systemic chemotherapy alone with manageable safety profile.

Bone mineral density as an individual prognostic biomarker in NSCLC patients treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) have left a deep impression in the treatment of non-small cell lung cancer (NSCLC), however, not all patients benefit from it. The purpose of this study was to investigate the prognostic value of baseline bone mineral density (BMD) derived from chest computed tomography (CT) scans in NSCLC patients treated with ICIs. Methods: This study included patients with advanced NSCLC who underwent ICI treatment at the Wuhan Union Hospital from March 2020 to October 2022. Baseline BMD was evaluated at non-contrast chest CT at the level of first lumbar vertebra. Patients were divided into BMD-lower group and BMD-higher group according to the optimal cutoff value calculated by X-tile software. Baseline characteristics of the two groups were compared and variables between the two groups were balanced by propensity score matching (PSM) analysis. We calculated the objective response rate (ORR) and disease control rate (DCR) of the two groups and analyzed overall survival (OS) and progression-free survival (PFS) using BMD and other clinical indexes through Cox regression models and Kaplan-Meier survival curves. Results: A total of 479 patients were included in this study, and all patients were divided into BMD-lower group (n=270) and BMD-higher group (n=209). After PSM analysis, each group consisted of 150 patients. ORR (43.3% vs. 43.5% before PSM, P = 0.964; 44.7% vs. 44.7% after PSM, P = 1.000) and DCR (91.1% vs. 94.3% before PSM, P = 0.195; 93.3% vs. 96.7% after PSM, P =0.190) were similar in two groups. There was no statistically significant relationship between BMD degree and PFS before (16.0 months vs. 18.0 months, P = 0.067) and after PSM analysis (17.0 months vs. 19.0 months, P = 0.095). However, lower BMD was associated with shorter OS both before (20.5 months vs. 23.0 months, P< 0.001) and after PSM analysis (20.0 months vs. 23.0 months, P = 0.008). Conclusion: Lower baseline BMD is associated with worse clinical outcomes in NSCLC patients treated with ICIs. As a reliable and easily obtained individual prognostic biomarker, BMD can become a routine detection indicator before immunotherapy.

Supernatural Beliefs-Based Intervention to Improve Type-2 Diabetes Self-Management: A Pilot Randomized Controlled Trial from China.

China has over 100 million people living with type 2 diabetes mellitus (T2DM). Interventions framed around pre-existing personal beliefs in the supernatural may improve T2DM self-management, but such interventions are lacking in China. This pilot randomized controlled trial (RCT) assessed the feasibility of a full-scale RCT to evaluate the efficacy of a supernatural beliefs-based intervention on T2DM management self-efficacy in China. In 2019, 62 T2DM patients were enrolled at two hospitals in Suzhou, China. Participants were randomly assigned to view a 30-s control or intervention video at baseline. The control video showed general diabetes self-management information. The intervention video showed identical information, but also indicated that some diabetics with supernatural beliefs (chao ziran xinnian) have lower glycemic levels, because their beliefs enhance their confidence in diabetes self-management. Development of the intervention was guided by the theory of planned behavior and literature on spiritual framing health interventions. Baseline and follow-up measures after two weeks were assessed by interviewer administered surveys in-person and by telephone, respectively. Diabetes management self-efficacy was assessed with the diabetes management self-efficacy scale. Randomization of intervention allocation appeared to be successful. However, follow-up retention was low, especially for the intervention group (3% vs. 31%). A full-size efficacy RCT using the current study design is unlikely to succeed. T2DM patients shown the supernatural beliefs-based intervention had significantly higher loss to follow-up that was insurmountable. T2DM patients in Suzhou, China may not be receptive to brief, non-tailored supernatural beliefs-based interventions delivered to a general population in clinical settings.

Non-small cell lung cancer and immune checkpoint inhibitor therapy: does non-alcoholic fatty liver disease have an effect?

BACKGROUND: Immunotherapy based on the application of immune checkpoint inhibitors (ICIs) is one of the standard treatments for advanced non-small cell lung cancer (NSCLC). Non-alcoholic fatty liver Disease (NAFLD) has demonstrated predictive value for response to immunotherapy in non-lung cancer types. Our study investigated the effect of NAFLD on the efficacy of real-life use of ICIs for patients with stage III / IV NSCLC. METHODS: The clinical and imaging data of patients with stage III / IV NSCLC who were first admitted to Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 2020 to July 2022 were retrospectively collected to ensure that they underwent at least one CT scan before treatment. A total of 479 patients were divided into the NAFLD group (Liver/Spleen density ratio ≤ 1) and the non-NAFLD group (Liver/Spleen density ratio > 1) by measuring the baseline liver and spleen CT value. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) of the patients were obtained. RESULTS: A total of 118 patients with NAFLD and 361 patients without NAFLD were included in the study. Patients with NAFLD tended to have higher BMI and higher total bilirubin compared to patients without NAFLD. The median duration of follow-up in the study was 22 m (IQR, 17-29 m). Both of 2 groups had a higher DCR (94% vs. 92%, p = 0.199) and ORR (38.1% vs. 44.9%, p = 0.452) respectively. There was no difference in efficacy between the two groups. In univariate analysis, NAFLD had no significant effect on PFS (p = 0.785) and OS (p = 0.851). Surprisingly, the presence of hypertension was observed to be associated with a higher OS (HR 1.471 95%CI 1.018-2.127, p = 0.040). Besides, based on multivariate analysis, lactic dehydrogenase was associated with PFS (HR 1.001 95%CI 1.000,1.002, p = 0.037) and OS (HR 1.002, 95%CI 1.001-1.003, p < 0.001). CONCLUSIONS: Among patients with NSCLC, NAFLD did not result in changes in survival or disease progression after immune checkpoint inhibitor therapy.

Prognosis and chemotherapy drug sensitivity in liver hepatocellular carcinoma through a disulfidptosis-related lncRNA signature.

Disulfidptosis, a new type of regulated cell death associated with the actin cytoskeleton, provides a new therapeutic tool for cancers. The direct relationship between disulfidptosis-related lncRNAs(DRLs) in liver hepatocellular carcinoma(HCC) remains unclear. We acquired transcriptomic data, corresponding clinical data, and tumor mutation data of HCC from the TCGA database. First of all, DRLs were determined through correlation analysis. Then, a prognostic model containing six DRLs was created by adopting univariate Cox regression, LASSO algorithm and multivariate Cox regression analysis. Based on the model, 424 HCC patients were divided into high- and low-risk groups. Next, we structured ROC curves and PCA through combining the model and clinical data. Enrichment analysis and immune infiltration analysis were adopted to further explore the relationship between the model and prognosis. In addition, we explored the relationship between the model and tumor mutation burden (TMB). There were significant differences between high- and low- risk groups, and patients in the high-risk group showed poor prognosis. Enrichment analysis suggested that metabolic progress was obviously different between the two groups. According to the analysis of immune infiltration, there were several differences in immune cells, function, and checkpoints. Patients with high-risk and high TMB demonstrated the least favorable prognosis. The two risk groups both manifested visiblly in chemotherapy drug sensitivity. To sum up, we set up a DRL-based signature and that may provide a predictable value for the prognosis and use of chemotherapy drugs for HCC patients.

Radiation Dose and Image quality of coronary CT angiography performed with whole-heart coverage CT scanner with 0.25s rotation time in patients with irregular heart rhythm.

Objectives: To evaluate radiation exposure, image quality, and diagnostic performance of coronary CT angiography (CCTA) using the invasive coronary angiography (ICA) as the reference standard in patients with irregular heart rhythm on a 0.25 s rotation time, 16 cm coverage, single-beat, CT scanner with AI-assisted motion correction. Methods: CCTA data-sheets of 427 patients using a CT scanner with an ECG monitoring system and motion correction algorithm were collected retrospectively. All the patients were divided into two groups: regular heart rhythm (357 patients) and irregular heart rhythm (70 patients). 22 patients in irregular heart rhythm underwent ICA. Image quality and effective dose in both groups were evaluated and compared. Image quality was evaluated on 5-point scales. The diagnostic performance of CCTA in irregular heart rhythm group was compared with the results of ICA. Results: The image quality in both groups was similar (4.34 ± 0.47 vs 4.37 ± 0.48, p > 0.05). No significant difference was observed in effective dose between two groups (2.7 ± 0.7 vs 2.9 ± 1.3, p > 0.05). The diagnostic accuracy was 90.91% in a patient-based analysis, 96.97% in a vessel-based analysis, and 98.61% in a segment-based analysis. In irregular heart rhythm group, gender was an important factor affecting the number of CCTA scans in a single examination and the radiation dose exposed to the patient. Conclusions: For patients with irregular heart rhythm, a CT scanner with an ECG monitoring system and motion correction algorithm can not only reduce the radiation dose to the same level as patients with normal heart rhythms, but also ensure that the images with high diagnostic accuracy.

The impact of pulmonary artery to ascending aorta diameter ratio progression on the prognosis of NSCLC patients treated with immune checkpoint inhibitors.

Background: Immunotherapy, represented by immune checkpoint inhibitors (ICIs), is a major breakthrough in cancer treatment. Studies have reported that the use of ICIs is associated with an increase in the pulmonary artery to ascending aorta diameter (PAD/AoD) ratio. However, the impact of PAD/AoD ratio progression on the prognosis of patients is unclear. Methods: This retrospective cohort study included patients with stage III or IV non-small cell lung cancer (NSCLC) treated with ICIs at the Wuhan Union Hospital between March 1, 2020, and September 1, 2022. The baseline and post-treatment PAD/AoD ratios of patients were evaluated through chest CT scans. The primary outcome of this study was overall survival (OS), while the secondary outcomes included progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Results: The PAD/AoD ratio increased after the initiation of ICIs (from 0.75 to 0.78; P < 0.001). A total of 441 patients were divided into severe group (n=221) and non-severe group (n=220) according to the median increase of PAD/AoD ratio (1.06). Compared with the non-severe group, the severe group had a lower DCR (87.8% vs. 96.0%, P = 0.005) and ORR (87.5% vs. 96.0%, P = 0.063). Over the entire duration of follow-up (median 22.0 months), 85 (38.5%) patients in the severe group and 30 (7.3%) patients in the non-severe group died. An increased PAD/AoD ratio was associated with shorter PFS (Hazard ratio (HR): 1.48 [95% CI, 1.14 to 1.93]; P = 0.003) and OS (HR: 3.50 [95% CI, 2.30 to 5.30]; P < 0.001). Similar results were obtained across subgroups. Conclusions: ICI treatment exacerbates an increase in the PAD/AoD ratio in patients with cancer, and greater increase in the PAD/AoD ratio was associated with a worse prognosis. PAD/AoD ratio could be a biomarker to stratify prognosis of NSCLC patients treated with ICIs.

Immune checkpoint inhibitors in cancer: the increased risk of atherosclerotic cardiovascular disease events and progression of coronary artery calcium.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have contributed to a significant advancement in the treatment of cancer, leading to improved clinical outcomes in many individuals with advanced disease. Both preclinical and clinical investigations have shown that ICIs are associated with atherosclerosis and other cardiovascular events; however, the exact mechanism underlying this relationship has not been clarified. METHODS: Patients diagnosed with stages III or IV non-small cell lung cancer (NSCLC) at the Wuhan Union Hospital from March 1, 2020, to April 30, 2022, were included in this retrospective study. Coronary artery calcium (CAC) volume and score were assessed in a subset of patients during non-ECG-gated chest CT scans at baseline and 3, 6, and 12 months after treatment. Propensity score matching (PSM) was performed in a 1:1 ratio to balance the baseline characteristics between the two groups. RESULTS: Overall, 1458 patients (487 with ICI therapy and 971 without ICI therapy) were enrolled in this cardiovascular cohort study. After PSM, 446 patients were included in each group. During the entire period of follow-up (median follow-up 23.1 months), 24 atherosclerotic cardiovascular disease (ASCVD) events (4.9%) occurred in the ICI group, and 14 ASCVD events (1.4%) in the non-ICI group, before PSM; 24 ASCVD events (5.4%) occurred in the ICI group and 5 ASCVD events (1.1%) in the non-ICI group after PSM. The CAC imaging study group comprised 113 patients with ICI therapy and 133 patients without ICI therapy. After PSM, each group consisted of 75 patients. In the ICI group, the CAC volume/score increased from 93.4 mm3/96.9 (baseline) to 125.1 mm3/132.8 (at 12 months). In the non-ICI group, the CAC volume/score was increased from 70.1 mm3/68.8 (baseline) to 84.4 mm3/87.9 (at 12 months). After PSM, the CAC volume/score was increased from 85.1 mm3/76.4 (baseline) to 111.8 mm3/121.1 (12 months) in the ICI group and was increased from 74.9 mm3/76.8 (baseline) to 109.3 mm3/98.7 (12 months) in the non-ICI group. Both cardiovascular events and CAC progression were increased after the initiation of ICIs. CONCLUSIONS: Treatment with ICIs was associated with a higher rate of ASCVD events and a noticeable increase in CAC progression.

Should the Baseline MRI Staging Criteria Differentiate Between Mucinous and Classical Rectal Adenocarcinoma?

RATIONALE AND OBJECTIVES: To compare baseline MR imaging features for pre-treatment staging between rectal mucinous adenocarcinoma (RMAC) and rectal classical adenocarcinoma (RCAC), and to investigate whether the subtype of mucinous carcinoma influences MRI evaluation criteria and high-risk tumors identifying. METHODS: A total of 306 patients who underwent surgical rectal cancer resection were retrospectively reviewed in the study. MR imaging parameters of the primary tumor and lymph nodes (LNs) were compared between two subtypes. Logistic regression and receiver operating characteristic analyses were performed to test significant associations between LN imaging parameters and malignant LN status in RMAC and RCAC, respectively. RESULTS: The length of mucinous tumors was larger than RCAC tumors in pT3 and pT4 stage. For pN0 patients, the long and short diameters of the largest LN on MRI were more likely to be larger in RCAC than RMAC. For pN+ patients, the proportion of LNs exhibiting internal heterogeneity in RMAC was obviously greater than that in RCAC. The best cut-off value of the largest short diameter of malignant LNs was 6.05 mm for RMAC and 8.05 mm for RCAC. And the highest AUC for predicting LNs metastases based on the largest short diameter was 0.794 for RMAC using 6 mm size cut-off, and 0.667 for RCAC using 8 mm cut-off. CONCLUSION: The imaging features that were associated with LN metastases were different between RMAC and RCAC, and different size criteria of LNs was suggested to distinguish high-risk tumors. Clinicians should stay vigilant of LN status and take histologic subtypes into consideration before assigning clinical strategies.

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

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

Exploring functional connectivity alterations in sudden sensorineural hearing loss: A multilevel analysis.

Sudden sensorineural hearing loss (SSNHL) constitutes an urgent otologic emergency, marked by a rapid decline of at least 30 dB across three consecutive frequencies within 72 h. While previous studies have noted brain region alterations encompassing both auditory and non-auditory areas, this research examines functional connectivity changes across integrity, network, and edge levels in SSNHL. The cohort included 184 participants: 107 SSNHL patients and 77 age- and sex-matched healthy controls. Our investigation comprises: (1) characterization of overall functional connectivity degree across 55 nodes in nine networks (p < 0.05, corrected for false discovery rate), exposing integrity level changes; (2) identification of reduced intranetwork connectivity strength within sensory and attention networks (somatomotor network, auditory network, ventral attention network, dorsal attention network) in SSNHL individuals (p < 0.05, Bonferroni corrected), and reduced internetwork connectivity across twelve distinct subnetwork pairs (p < 0.05, FDR corrected); (3) revelation of increased internetwork connectivity in SSNHL patients, primarily spanning dorsal attention network, fronto parietal network, default mode network, and limbic network, alongside widespread reductions in connectivity patterns among the nine distinct resting-state brain networks. The study further uncovers negative correlations between SSNHL duration and intranetwork connectivity of the auditory network (p < 0.001, R = -0.474), and between Tinnitus Handicap Inventory (THI) scores and internetwork connections linking auditory network and dorsal attention network (p < 0.001, R = -0.331). These observed alterations provide crucial insights into the neural mechanisms underpinning SSNHL and extend our comprehension of the brain's network-level responses to sensory loss. By unveiling the intricate interplay between sensory deprivation, adaptation, and cognitive processes, this study lays the groundwork for future research targeting enhanced diagnosis, treatment, and rehabilitation approaches for individuals afflicted by SSNHL.

Beneficial effects of ginkgetin on improving nonalcoholic steatohepatitis characterized by bulk and single-cell RNA sequencing analysis.

Background and aims: Nonalcoholic steatohepatitis (NASH) has become one of the major causes of cirrhosis and liver failure. However, there are currently no approved medications for managing NASH. Our study was designed to assess the effects of ginkgetin on NASH and the involved mechanisms. Methods: We constructed a mouse model of NASH by high-fat diet for 24 weeks. The effects of ginkgetin on NASH were evaluated by histological study, Western blot, and biochemical analysis. RNA Sequencing (RNA-Seq) analysis was used to investigate the alteration in gene expression and signaling pathways at bulk and single-cell levels. Results: Administration of ginkgetin resulted in a marked improvement in hepatic lipid accumulation, inflammation, and fibrosis in the NASH model. And these results were supported by bulk RNA-Seq analysis, in which the related signaling pathways and gene expression were markedly downregulated. Furthermore, single-cell RNA-Seq (scRNA-Seq) analysis revealed that the effects of ginkgetin on NASH were associated with the reprogramming of macrophages, hepatic stellate cells, and endothelial cells. Especially, ginkgetin induced a marked decrease in macrophages and a shift from pro-inflammatory to anti-inflammatory phenotype in NASH mice. And the NASH-associated macrophages (NAMs), which emerge during NASH, were also significantly downregulated by ginkgetin. Conclusion: Ginkgetin exhibits beneficial effects on improving NASH, supported by bulk and single-cell RNA-Seq. Our study may promote pharmacological therapy for NASH and raise the existent understanding of NASH.

Robotic versus open surgery for simultaneous resection of rectal cancer and liver metastases: a randomized controlled trial.

OBJECTIVE: This study aimed to compare the short-term and long-term outcomes between robotic-assisted simultaneous resection and open surgery in patients with rectal cancer and liver metastases. BACKGROUND: Open simultaneous resection of colorectal cancer and synchronous liver metastases is widely performed and the potential cure for eligible patients. However, the feasibility of robotic simultaneous resection of primary and secondary liver lesions has not been established as a treatment option for metastatic rectal cancer. PATIENTS AND METHODS: A single-center randomized controlled trial was conducted at a hospital in China. Enrolling patients were aged from 18 to 75 years and diagnosed with surgically resectable metastatic rectal cancer (distal extension to ≤15 cm from the anal margin). Patients selected for simultaneous resection were randomly assigned to have robotic or open surgery at a 1:1 ratio. The primary endpoint was the incidence rate of complications within 30 days after surgery. Secondary endpoints were bladder, sexual function, 3-year disease-free survival, and overall survival. RESULTS: A total of 171 patients were enrolled in this trial with 86 in the robotic group and 85 in the open group. As a result, patients in the robotic group demonstrated fewer complications within 30 days after surgery than those in the open group (31.4 vs. 57.6%, P =0.014) and no mortality seen in either group. Patients in the robotic group had less blood loss [mean (SD), 125.5 (38.3) vs. 211.6 (68.7) ml; P <0.001], faster bowel function recovery [mean (SD), 63.7 (27.4) vs. 93.8 (33.5) h P <0.001] and shorter hospital stay [mean (SD), 8.0 (2.2) vs. 10.7 (5.4) days; P <0.001] compared with those in the open group. The robotic group had a faster recovery of bladder and sexual function at 3 months after surgery than that of the open group. The 3-year disease-free survival rate (39.5 vs. 35.3%, P =0.739) and the 3-year overall survival rate (76.7 vs. 72.9%, P =0.712) were not statistically significant between the two groups. CONCLUSIONS: In our randomized clinical trial, robotic simultaneous resection treatment of patients with rectal cancer and liver metastases resulted in fewer surgical complications, and a faster recovery to those of open surgery. Oncological outcomes showed no significant difference between the two groups.

CT Findings of Undifferentiated Pancreatic Cancer With Osteoclast-Like Giant Cells: A Case Series from a Single Center's Experience With 10 Cases.

Little is known about the imaging features of undifferentiated carcinoma with osteoclast-like giant cells of the pancreas (UCOGCP) because of its extremely low incidence. To improve the diagnostic accuracy of this tumor, 10 UCOGCP cases with confirmed histopathology were collected and their clinical and image data features were analyzed. We found that the median age of our study was 61 years (50-76 years in range) and the main clinical manifestations were nonspecific abdominal pain. There were some differences in the degree of enhancement and computed tomography (CT) features between the tumor located at the head and body or tail of the pancreas. Perhaps these subtle imaging findings can provide valuable diagnostic information.

Reversion of liver cirrhosis after endovascular treatment in Chinese patients with Budd-Chiari syndrome.

AIMS: To investigate the impact of endovascular (EV) treatment on liver cirrhosis in Chinese patients with Budd-Chiari syndrome (BCS). METHODS: From September 2011 to March 2022, 97 patients from four hospitals in China who were diagnosed with primary BCS complicated with liver cirrhosis and received EV treatment were retrospectively enrolled in this study for clinical analysis. In addition, liver tissues for basic research were acquired from 25 patients between June 2022 and March 2023, including six with benign liver tumors, 11 with BCS before EV treatment, and eight with EV-treated BCS. Liver cirrhosis was assessed by clinical outcomes, histological studies, and the expression of related genes at the mRNA and protein levels. RESULTS: The patients with BCS had better liver function after EV treatment, evidenced by an increased albumin level and reduced total bilirubin, ALT, and AST. The imaging findings suggested an amelioration of liver cirrhosis and portal hypertension, including increased portal vein velocity (13.52 ± 8.89 cm/s vs. 17.51 ± 6.67 cm/s, p < 0.001) and decreased liver stiffness (30.37 ± 6.39 kPa vs. 23.70 ± 7.99 kPa, p < 0.001), portal vein diameter (14.97 ± 3.42 mm vs. 13.36 ± 2.89 mm, p < 0.001), and spleen volume (870.00 ± 355.61 cm3 vs. 771.36 ± 277.45 cm3 , p < 0.001). Furthermore, histological studies revealed that EV treatment resulted in a restoration of liver architecture with reduced extracellular matrix deposition. Meanwhile, hepatic angiogenesis and inflammation, which have a close relationship with cirrhosis, were also inhibited. In addition, the state of hepatocytes switches from apoptosis to proliferation after EV treatment. CONCLUSIONS: BCS-induced liver cirrhosis could be reversed by EV treatment from macroscopic to microscopic dimensions. Our study may provide further insights into understanding BCS and treating cirrhosis.

Preoperative chemotherapy prior to primary tumour resection for asymptomatic synchronous unresectable colorectal liver-limited metastases: The RECUT multicenter randomised controlled trial.

PURPOSE: Primary tumour resection (PTR) is still a selection for patients with low tumour burden and good condition, especially with conversion therapy purpose for colorectal liver-limited metastases (CRLMs). The objective was to evaluate whether pre-PTR chemotherapy could improve progression-free survival (PFS) for patients with asymptomatic synchronous unresectable CRLMs. PATIENTS AND METHODS: Patients with asymptomatic synchronous unresectable CRLMs were randomly assigned to receive pre-PTR chemotherapy (arm A) or upfront PTR (arm B). Chemotherapy regimens of mFOLFOX6 plus cetuximab, mFOLFOX6 plus bevacizumab or mFOLFOX6 alone were chosen according to the RAS genotype. The primary end-point was PFS; secondary end-points included overall survival (OS), tumour response, disease control rate (DCR), liver metastases resection rate, surgical complications and chemotherapy toxicity. RESULTS: Three hundred and twenty patients were randomly assigned to arm A (160 patients) and arm B (160 patients). Patients in arm A had significantly improved the median PFS compared with arm B (10.5 versus 9.1 months; P = 0.013). Patients in arm A also had significantly better DCR (84.4% versus 75.0%; P = 0.037). The median OS (29.4 versus 27.2 months; P = 0.058), objective response rate (ORR) (53.1% versus 45.0%; P = 0.146) and liver metastases resection rate (21.9% versus 18.1%; P = 0.402) were not significantly different. The Clavien-Dindo 3-4 complications post PTR (4.5% versus 3.8%, P = 0.759) and the incidence of grade 3/4 chemotherapy events (42.2% versus 40.4%, P = 0.744) reached no statistical significance. CONCLUSIONS: For asymptomatic synchronous unresectable CRLMs, Pre-PTR chemotherapy improved the PFS compared with upfront PTR.

Transarterial Chemoembolization Combined with Apatinib for Treatment of Advanced Hepatocellular Carcinoma: Analysis of Survival and Prognostic Factors.

OBJECTIVE: Apatinib is a novel inhibitor of vascular endothelial growth factor receptor-2. The goal of this study was to evaluate overall survival (OS) after a combination of transarterial chemoembolization (TACE) and apatinib in patients with advanced hepatocellular carcinoma (HCC) and to identify the factors affecting patient survival. METHODS: Fifty-one patients with advanced HCC who received TACE in combination with apatinib in our hospital from June 2015 to May 2017 were enrolled. The OS and progression-free survival (PFS) were calculated using the Kaplan-Meier method. The log-rank test and Cox regression model were used to determine the factors affecting OS. RESULTS: The median OS and PFS of the patients were 15 months and 10 months, respectively. The 1-, 2-, and 3-year survival rates were 64.7%, 23.5%, and 1.8%, respectively. Univariate survival analysis showed that patients with Child-Pugh A (P=0.006), reduction rate of proper hepatic artery (P=0.016), hand-foot syndrome (P=0.005), secondary hypertension (P=0.050), and without ascites (P=0.010) had a better OS. Multivariate analysis showed that hand-foot syndrome (P=0.014), secondary hypertension (P=0.017), and reduction rate of proper hepatic artery (P=0.025) were independent predictors of better OS. CONCLUSION: TACE combined with apatinib is a promising treatment for advanced HCC. Hand-foot syndrome, secondary hypertension, and the reduction rate of proper hepatic artery were associated with a better OS.

Arterial enhancement fraction in evaluating the therapeutic effect and survival for hepatocellular carcinoma patients treated with DEB-TACE.

BACKGROUND: Arterial enhancement fraction (AEF), derived from triphasic CT scans, is considered to indirectly reflect the ratio of hepatic arterial perfusion to total perfusion. The purpose of this study was to retrospectively investigate the relationship between AEF and treatment response and survival in hepatocellular carcinoma (HCC) patients treated with drug-eluting bead (DEB) TACE. METHODS: AEF of primary lesion (AEFpre) and residual tumor (AEFpost) in 158 HCC patients were obtained from triphasic liver CT examinations pre- and post-treatment. Wilcoxon-signed rank test was used to compare the AEFpre and AEFpost for different response groups. Survival curves for overall survival (OS) in patients with different AEF were created by using Kaplan-Meier method. Cox regression analyses were used to determine the association between AEF and OS. RESULTS: There was no correlation between AEFpre and treatment response. After DEB-TACE, AEFpost was significantly lower than AEFpre either in the partial response group (38.9% vs. 52.7%, p <  0.001) or in the stable disease group (49.3% vs. 52.1%, p = 0.029). In the progression disease group, AEFpost was numerically higher than AEFpre (55.5% vs. 53.0%, p = 0.604). Cox regression analyses showed that risk of death increased in patients with AEFpre > 57.95% (HR = 1.66, p = 0.019) or AEFpost > 54.85% (HR = 2.47, p <  0.001), and the risk reduced in patients with any reduction in tumor AEF (decrease ratio ≥ 0) and with increased AEF but not exceeding the ratio of 0.102 (increase ratio <  0.102) (HR = 0.32, p <  0.001). CONCLUSIONS: The change in AEF of viable tumor is correlated with response of HCC to DEB-TACE. In addition, the AEF could be a helpful predictor in future studies on the embolization treatment for HCC.