Objectives
To evaluate the relationship between contrast-enhanced (CE) ultrasound Liver Reporting and Data System (LI-RADS) classification of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and ...their histopathological component predominance, and to determine if the CEUS LI-RADS category can be used to predict the patient’s survival after surgical resection.
Methods
Between January 2011 and December 2018, medical records and CEUS of patients with pathologically proven cHCC-CCA were studied. The predominance of hepatocellular carcinoma (HCC)/intrahepatic cholangiocarcinoma (ICC) component of cHCC-CCA was analyzed by histopathology. The proportion of HCC-predominant cHCC-CCA in different LI-RADS category was compared by using Fisher’s exact test. Factors affecting tumor recurrence were analyzed by Cox proportional hazard model. Disease-free survival (DFS) was estimated by using Kaplan-Meier survival curve and compared by log-rank test.
Results
The study included 37 cHCC-CCA patients (33 men, 4 women; average age, 50.4 ± 11.0 years) and 37 nodules (mean diameter, 6.1 ± 3.9 cm). According to CEUS LI-RADS, 62.2% (23/37), 18.9% (7/37), and 18.9% (7/37) of cHCC-CCA were classified as LR-M, LR-5, and LR-TIV, respectively. The ratio of HCC predominance in LR-5 was 100% (10/10) vs 81.5% (22/27) in the LR-M group (
p
= 0.591). In our population, LR-5 patients had longer DFS than LR-M and LR-TIV patients combined (median DFS: 18.0 vs 6.4 months,
p
= 0.016). Multiple lesions (hazard ratio, 3.1;
p
= 0.007), tumor size (≥ 5 cm, hazard ratio, 4.1;
p
= 0.003), and CEUS LI-RADS category (LR-M and LR-TIV, hazard ratio, 4.7;
p
= 0.011) showed independent association with shorter DFS.
Conclusion
cHCC-CCA characterized as LR-5 on CEUS tend to represent HCC-predominant tumors with significantly longer disease-free survival compared to cHCC-CCA categorized as LR-M and LR-TIV.
Key Points
•
By using the American College of Radiology contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS), majority (30/37, 81.1%) of cHCC-CCA tumors were classified as LR-M or LR-TIV and only 18.9% (7/30) of cHCC-CCA were categorized as LR-5.
•
Patients with CEUS LR-5 cHCC-CCA had statistically significant longer disease-free time than those with LR-M and TIV cHCC-CCA (median DFS: 18.0 vs 6.4 months, p = 0.016).
•
Multiple lesions (hazard ratio, 3.1; p = 0.007), tumor size (≥ 5 cm, hazard ratio, 4.1; p = 0.003), and CEUS LI-RADS category (LR-M and LR-TIV, hazard ratio, 4.7; p = 0.011) showed independent association with shorter DFS.
Hepatocellular carcinoma (HCC), one of the most common lethal diseases in the world, has a 5-year survival rate of only 7%. Hepatocellular carcinoma has no symptoms in the early stage but obvious ...symptoms in the late stage, leading to delayed diagnosis and reduced treatment efficacy. In recent years, as the scope of HCC research has increased in depth, the clinical development and application of molecular targeted drugs and immunotherapy drugs have brought new breakthroughs in HCC treatment. Targeted therapy drugs for HCC have high specificity, allowing them to selectively kill tumor cells and minimize damage to normal tissues. At present, these targeted drugs are mainly classified into 3 categories: small molecule targeted drugs, HCC antigen-specific targeted drugs, and immune checkpoint targeted drugs. This article reviews the latest research progress on the targeted drugs for HCC.
IMPORTANCE: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of ...relapse and death are needed. OBJECTIVE: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. INTERVENTIONS: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. RESULTS: Among 443 women who were randomized, 434 were included in the full analysis set (mean SD age, 46 9.9 years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio HR for risk of recurrence or death, 0.64 95% CI, 0.42-0.95; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 95% CI, 0.38-0.92; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 95% CI, 0.47-1.19; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 95% CI, 0.46-1.13; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. CONCLUSIONS AND RELEVANCE: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01112826
Long-chain non-coding RNAs (lncRNAs) are RNA molecules with a length greater than 200 nt and no function of encoding proteins. lncRNAs play a precise regulatory function at different levels of ...transcription and post-transcription, and they interact with various regulatory factors to regulate gene expression, and then participate in cell growth, differentiation, apoptosis, and other life processes. In recent years, studies have shown that the abnormal expression of lncRNAs is closely related to the occurrence and development of tumors, which is expected to become an effective biomarker in tumor diagnosis. The sequencing analysis of mutations in the whole tumor genome suggests that mutations in non-coding regions may play an important role in the occurrence and development of tumors. Therefore, in-depth study of lncRNAs is helpful to clarify the molecular mechanism of tumor occurrence and development and to provide new targets for tumor diagnosis and treatment. This review introduces the molecular mechanism and clinical application prospect of lncRNAs affecting tumor development from the perspective of gene expression and regulation.
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lncRNAs play a precise regulatory function at different levels of transcription and post-transcription and participate in cell growth, differentiation, and apoptosis, and are related to the occurrence and development of tumors, which is expected to become an effective biomarker in tumor diagnosis and treatment.
Low-intensity pulsed ultrasound (LIPUS) accelerates fracture healing by stimulating the production of bone callus and the mineralization process. This study compared a novel bimodal acoustic signal ...(BMAS) device for bone fracture healing to a clinical LIPUS system (EXOGEN; Bioventus, Durham, NC, USA). Thirty rabbits underwent a bilateral fibular osteotomy. Each rabbits' legs were randomized to receive 20-min treatment daily for 18 days with BMAS or LIPUS. The latter utilizes a longitudinal ultrasonic mode only, while the former employs ultrasound-induced shear stress to promote bone formation. Power Doppler imaging (PDI) was acquired days 0, 2, 4, 7, 11, 14, and 18 post-surgery to monitor treatment response and quantified off-line. X-rays were acquired to evaluate fractures on days 0, 14, 18, and 21. Seventeen rabbits completed the study and were euthanized day 21 post-surgery. The fibulae were analyzed to determine maximum torque, initial torsional stiffness, and angular displacement at failure. ANOVAs and paired t-tests were used to compare pair-wise outcome variables for the two treatment modes on a per rabbit basis. The BMAS system induced better fracture healing with greater stiffness (BMAS 0.21 ± 0.19 versus LIPUS 0.16 ± 0.19 <inline-formula> <tex-math notation="LaTeX">\text{N}\cdot </tex-math></inline-formula>cm/°, <inline-formula> <tex-math notation="LaTeX">{p} =0.050 </tex-math></inline-formula>) and maximum torque (BMAS 7.84 ± 5.55 versus LIPUS 6.26 ± 3.46 <inline-formula> <tex-math notation="LaTeX">\text{N}\cdot </tex-math></inline-formula>cm, <inline-formula> <tex-math notation="LaTeX">{p} =0.022 </tex-math></inline-formula>) than the LIPUS system. Quantitative PDI assessments showed a higher amount of vascularity with LIPUS than BMAS on days 4 and 18 (<inline-formula> <tex-math notation="LaTeX">{p} < 0.04 </tex-math></inline-formula>). In conclusion, the novel BMAS technique achieved better bone fracture healing response than the current Food and Drug Administration (FDA)-approved LIPUS system.
Increase the equivalence ratio is a good way to improve performance of turbocharged hydrogen engines at low engine speeds. To explore the feasibility of this strategy, this paper investigated the ...experimental data of a 2.3 L turbocharged port fuel injection (PFI) hydrogen engine at 1500 rpm and 2000 rpm. The results showed that the power can increase from 6.8 kW to 21 kW at 2000 rpm and from 6.4 kW to 16.5 kW at 1500 rpm with increasing of the equivalence ratio. However, the equivalence ratio corroding to the biggest power is 0.8 at 1500 rpm and 0.9 at 2000 rpm because the turbocharged pressure and the volumetric efficiency at 2000 rpm are higher than the ones at 1500 rpm. The biggest BTE can reach to 30.1% at 2000 rpm and 29.3% at 1500 rpm within the range of 0.65–0.8. The covariance of indicated mean effective pressure (CoVimep) of turbocharged hydrogen is lower than 1.5% at low engine speeds and the combustion stability increased with the increase of equivalence ratio. The NOx can be reduced from 877 ppm to 0 ppm at 1500 rpm and from 1259 ppm to 17 ppm at 2000 rpm, which means the reduction efficiency of H2+TWC can exceed 99%.
•The biggest power is influence by the sum of hydrogen and air mass.•The biggest BTE can reach to 30% with λ = 0.65–0.8 at 1500 rpm and 2000 rpm.•H2+TWC can reduce the NOx more than 99% at λ > 1.•The CoVIMEP of turbocharged hydrogen is lower than 1.5% at low engine speeds.
Ophiolites worldwide show striking diversities in their rock assemblage and structure (i.e., ophiolite diversity), raising a question whether ophiolites are originally similar before intense tectonic ...dismemberment. Comparison between ophiolites and oceanic lithospheres at modern mid-ocean ridges may provide key constraints on the origin of ophiolite diversity, because oceanic lithospheric structures are inherently controlled by spreading rates. Here, we present a case study of the Xigaze ophiolite in southern Tibet focusing on its gabbroic intrusions outcropping in three localities, i.e., Dazhuqu, Baigang and Jiding. Compared to the Jiding sequence, the Dazhuqu and Baigang gabbroic rocks are less evolved, characterized by higher Cr
2
O
3
contents but lower contents of TiO
2
and rare earth element in both clinopyroxene and bulk compositions. It is evident, hence, that the Xigaze ophiolite is characterized by variably evolved and discontinuously distributed gabbroic intrusions, rather by a continuous lower oceanic crust between the mantle and sheeted dike complex as the Penrose-type ophiolites. Our study, along with the identification in previous studies of oceanic detachment faults within the Xigaze ophiolite, demonstrates that the Xigaze ophiolite shows close similarities to oceanic lithospheres at modern slow- and ultraslow-spreading ridges. Hence, the significant structural distinctions between the Xigaze ophiolite and the Penrose-type ophiolites (e.g., the Oman ophiolite) may be inherently associated with different spreading rates of paleo-ridges. Considering the limited scale of the Xigaze gabbroic rocks, here we suggest the Xigaze ophiolite as a typical representative of fossil ultraslow-spreading ridges.
Previous evidence has highlighted M2 macrophage regulation of cancer cells via exosome shuttling of microRNAs (miRNAs or miRs). The current study set out to explore the possible role of M2 ...macrophage-derived exosomal miR-155-5p in regard to immune escape of colon cancer cells. Experimental data from quantitative reverse-transcriptase PCR (qRT-PCR) and western blot analysis revealed highly expressed miR-155-5p and interleukin (IL)-6 and poorly expressed ZC3H12B in M2 macrophage-derived exosomes. Additionally, miR-155-5p could be transferred by M2 macrophage-isolated exosomes to colon cancer cells, which targeted ZC3H12B by binding to the 3¢ UTR, as identified by dual luciferase reporter gene. Meanwhile, gain- and loss-of function experimentation on miR-155-5p and ZC3H12B in SW48 and HT29 cells cocultured with M2 macrophage-secreted exosomes demonstrated that miR-155-5p overexpression or ZC3H12B silencing promoted the proliferation and antiapoptosis ability of SW48 and HT29 cells, as well as augmenting the CD3+ T cell proliferation and the proportion of interferon (IFN)-γ+ T cells. Xenograft models confirmed that M2 macrophage-derived exosomal miR-155-5p reduced the ZC3H12B expression to upregulate IL-6, which consequently induced immune escape and tumor formation. Collectively, our findings indicated that M2 macrophage-derived exosomal miR-155-5p can potentially promote the immune escape of colon cancer by impairing ZC3H12B-mediated IL-6 stability reduction, thereby promoting the occurrence and development of colon cancer.
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miR-155-5p was transferred by M2 macrophage-derived exosomes into colon cancer cells, where miR-155-5p targeted ZC3H12B, which in turn negatively regulated the stability of IL-6 mRNA. By this mechanism, miR-155-5p inhibited T cell immune response and thus promoted immune escape in colon cancer.
Traditional methods of cancer treatment are usually based on the morphological and histological diagnosis of tumors, and they are not optimized according to the specific situation. Precision medicine ...adjusts the existing treatment regimen based on the patient’s genomic information to make it most suitable for patients. Detection of genetic mutations in tumors is the basis of precise cancer medicine. Through the analysis of genetic mutations in patients with cancer, we can tailor the treatment plan for each patient with cancer to maximize the curative effect, minimize damage to healthy tissues, and optimize resources. In recent years, next-generation sequencing technology has developed rapidly and has become the core technology of precise targeted therapy and immunotherapy for cancer. From early cancer screening to treatment guidance for patients with advanced cancer, liquid biopsy is increasingly used in cancer management. This is as a result of the development of better noninvasive, repeatable, sensitive, and accurate tools used in early screening, diagnosis, evaluation, and monitoring of patients. Cell-free DNA, which is a new noninvasive molecular pathological detection method, often carries tumor-specific gene changes. It plays an important role in optimizing treatment and evaluating the efficacy of different treatment options in clinical trials, and it has broad clinical applications.
Small intestinal ischemia is a challenging diagnosis to make, even with the combination of imaging, laboratory analysis, and physical exam. This pilot study investigated the role of CEUS in ...evaluating small bowel wall vascularity in participants with suspected ischemia.
In this IRB-approved pilot study, CEUS using perflutren lipid microspheres (DEFINITY®; Lantheus Medical Imaging Inc., N. Billerica, MA) was performed on participants determined by the clinical surgical team to have concerns for small intestinal ischemia. CEUS interpretations were performed at both the bedside and later by a blinded radiologist and compared to clinical imaging, surgical findings, or long-term clinical outcomes.
Fifteen CEUS examinations were performed on 14 participants. Five of the participants underwent exploratory laparotomy. Of these, one had small intestinal ischemia (without necrosis). Point of care CEUS demonstrated no evidence of bowel necrosis in any case, and delayed enhancement (indicative of intestinal ischemia) in three cases, resulting in a sensitivity of 100% (95% CI 2.5-100%) and specificity of 85.7% (95% CI 57.2-98.2%). CEUS correctly ruled out ischemia in 91.7% of cases with CT suspicion of small bowel obstruction and 60% of cases that underwent surgical intervention. Additionally, the rate of agreement between bedside interpretation and later radiologist read was high (93%).
CEUS is uniquely positioned for evaluating the small intestine, because of its high temporal resolution and immediacy of results. Combined with multi-sectional imaging for focal areas of ischemia and/or clinical suspicion for pan ischemia, CEUS may be a useful rule out test for small intestinal ischemia.
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