Mechanical confinement promotes heat resistance of hepatocellular carcinoma via SP1/IL4I1/AHR axis.

Mechanical stress can modulate the fate of cells in both physiological and extreme conditions. Recurrence of tumors after thermal ablation, a radical therapy for many cancers, indicates that some tumor cells can endure temperatures far beyond physiological ones. This unusual heat resistance with unknown mechanisms remains a key obstacle to fully realizing the clinical potential of thermal ablation. By developing a 3D bioprinting-based thermal ablation system, we demonstrate that hepatocellular carcinoma (HCC) cells in this 3D model exhibit enhanced heat resistance as compared with cells on plates. Mechanistically, the activation of transcription factor SP1 under mechanical confinement enhances the transcription of Interleukin-4-Induced-1, which catalyzes tryptophan metabolites to activate the aryl hydrocarbon receptor (AHR), leading to heat resistance. Encouragingly, the AHR inhibitor prevents HCC recurrence after thermal ablation. These findings reveal a previously unknown role of mechanical confinement in heat resistance and provide a rationale for AHR inhibitors as neoadjuvant therapy.

Visceral adipose volume is correlated with surgical tissue fibrosis in Crohn's disease of the small bowel.

Background: This study explored the diagnostic performance of visceral adiposity to predict the degree of intestinal inflammation and fibrosis. Methods: The patients with Crohn's disease (CD) who underwent surgical small bowel resection at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between January 2007 and December 2017 were enrolled. We evaluated the intestinal imaging features of computed tomography enterography (CTE), including mesenteric inflammatory fat stranding, the target sign, mesenteric hypervascularity, bowel wall thickening, lymphadenopathy, stricture diameter, and maximal upstream diameter. We used A.K. software (Artificial Intelligence Kit, version 1.1) to calculate the visceral fat (VF) and subcutaneous fat (SF) volumes at the third lumbar vertebra level. Pathological tissue information was recorded. Diagnostic models were established based on the multivariate regression analysis results, and their effectiveness was evaluated by area under the curve (AUC) and decision curve analyses. Results: Overall, 48 patients with CD were included in this study. The abdominal VF/SF volume ratio (odds ratio, 1.20; 95% confidence interval, 1.05-1.38; P = 0.009) and the stenosis diameter/upstream intestinal dilatation diameter (ND) ratio (odds ratio, 0.90; 95% confidence interval, 0.82-0.99; P = 0.034) were independent risk factors for the severe fibrosis of the small intestine. The AUC values of the VF/SF ratio, the ND ratio, and their combination were 0.760, 0.673, and 0.804, respectively. The combination of the VS/SF volume ratio and ND ratio achieved the highest net benefit on the decision curve. Conclusion: The VF volume on CTE can reflect intestinal fibrosis. The combination of the VF/SF volume ratio and ND ratio of CD patients assessed using CTE can help predict severe fibrosis stenosis of the small intestine.

The presence of microvascular invasion guides treatment strategy in recurrent HBV-related HCC.

OBJECTIVES: We used the status of microvascular invasion (MVI) at primary resection to help treatment selection for hepatitis B virus-positive (HBV+) recurrent hepatocellular carcinoma (rHCC) patients in Barcelona Clinic Liver Cancer (BCLC) stage B-C. METHODS: From 2009 to 2017, we enrolled 221 consecutive HBV+ rHCC patients at BCLC stage B-C who underwent re-resection (RR), radiofrequency ablation (RFA), or transarterial chemoembolization (TACE). Post recurrence survival (PRS) and overall survival (OS) were compared between RR/RFA and TACE according to MVI status. A one-to-one propensity score matching analysis was performed. RESULTS: For MVI(-) patients, the median PRS was 62.3 months for the RR/RFA group and 21.1 months for the TACE group (p = 0.039). The corresponding OS was 71.4 months and 26.6 months, respectively (p = 0.010). For MVI(+) patients, the median PRS in the RR/RFA group and TACE group was 14.7 months and 10.1 months (p = 0.115). The corresponding OS was 23.4 months and 16.4 months, respectively (p = 0.067). After matching, the dominance of RR/RFA over TACE remained in MVI(-) patients for both PRS (62.3 months vs 15.3 months, p = 0.019) and OS (98.1 months vs 33.4 months, p = 0.046). No significant difference was found in MVI(+) patients for either PRS (14.7 months vs 11.8 months, p = 0.593) or OS (23.4 months vs 28.1 months, p = 0.662). CONCLUSIONS: MVI status definitely helps select treatment options in HBV+ rHCC patients. For MVI(-) patients, RR/RFA provided better survival than TACE while for MVI(+) patients, TACE shared similar survival outcomes. KEY POINTS: • This study aimed at the determination of the optimal treatment options (ablation /resection vs TACE) in case of recurrent HBV-related HCC. • It showed that MVI status, established at primary resection of HCC, was a powerful marker for selecting the best treatment option in these patients. • In MVI(-) patients, RR/RFA achieved a better survival than TACE. In MVI(+) patients, TACE shared similar survival.

[Association of the ALOX5AP gene SG13S114 A/T polymorphism with atherosclerosis].

OBJECTIVE: To investigate the relationship between the polymorphism of SG13S114 A/T in the 5-lipoxygenase-activating protein (ALOX5AP) gene and the stability of carotid atherosclerosis. METHODS: Polymorphism of SG13S114 A/T in the ALOX5AP gene was analyzed in 152 cases of acute infarction with stable plaque, and 132 cases of acute infarction with vulnerable plaques, by using polymerase chain reaction and restriction fragment length polymorphism. Carotid artery plaque was analyzed by carotid artery color ultrasound. RESULTS: The frequencies of SG13S114 AA genotype and the A allele in the vulnerable plaque group were higher than that in the stable plaque group (P< 0.01). CONCLUSION: The polymorphism of SG13S114 A/T in the ALOX5AP gene may be associated with the instability of atherosclerosis. And the SG13S114 A allele may be a risk factor of vulnerable plaques.