Eliciting Older Cancer Patients' Preferences for Follow-Up Care to Inform a Primary Healthcare Follow-Up Model in China: A Discrete Choice Experiment.

BACKGROUND AND OBJECTIVES: Increasing longevity and advances in treatment have increased the cancer burden in the elderly, resulting in complex follow-up care needs; however, in China, little is known about the follow-up care preferences of these patients. This study quantified older cancer patients' preferences for follow-up care and examined the trade-offs they are willing to make to accept an alternative follow-up model. METHODS: A discrete choice experiment was conducted among inpatients aged over 60 years with breast, prostate, or colorectal cancer, at two large tertiary hospitals in Nantong, China. Preference weights for follow-up care were estimated using mixed logit analysis. Subgroup analysis and latent class analysis were used to explore preference heterogeneity. RESULTS: Complete results were obtained from 422 patients (144 with breast cancer, 133 with prostate cancer, 145 with colorectal cancer), with a mean age of 70.81 years. Older cancer patients stated a preference for follow-up by specialists over primary healthcare (PHC) providers ( ß = -1.18, 95% confidence interval -1.40 to -0.97). The provider of follow-up care services was the most valued attribute among patients with breast cancer (relative importance [RI] 37.17%), while remote contact services were prioritized by patients with prostate (RI 43.50%) and colorectal cancer (RI 33.01%). The uptake rate of an alternative care model integrating PHC increased compared with the baseline setting when patients were provided with preferred services (continuity of care, individualized care plans, and remote contact services). CONCLUSION: To encourage older cancer patients to use PHC-integrated follow-up care, alternative follow-up care models need to be based on patients' preferences before introducing them as a routine option.

Development of a contrast-enhanced ultrasound guided high intensity focused ultrasound system for coagulation of liver parenchyma.

BACKGROUND: The liver is the most common organ injured in blunt abdominal trauma and makes up roughly 5% of all trauma admissions. Current treatments are invasive and resource-intensive, which may delay care. We aim to develop and validate a contrast-enhanced ultrasound (CEUS)guided noninvasive tool to treat liver lacerations at the bedside. METHODS: Two 1.8 MHz high-intensity focused ultrasound (HIFU) elements were coupled to a C1-6 diagnostic ultrasound probe and a Logiq E10 scanner (GE HealthCare) utilizing a custom enclosure for co-registered imaging and ablation. A phantom was created from polyacrylamide gel combined with thermochromic ink whose color changes above biological ablative temperatures (60 °C). The HIFU wave was focused approximately 0.5 cm below the surface utilizing a 50% duty cycle generating 11.9 MPa for 20, 30, 40, 50, and 60s. Experiments were repeated on ex vivo chicken livers in a water bath. Finally, the livers of 4 live swine underwent up to 6 CEUS-guided treatments using parameters optimized from in vitro work. RESULTS: Treatment of the phantom between 20-60s, produced ablation sizes from 0.016 to 0.4 cm 3 . The relationship between time and size was exponential (R 2 = 0.992). Ablation areas were also well visualized on with ultrasound imaging. The ex vivo liver ablation size at 20s was 0.37 cm 3 , at 30s was 0.66 cm 3 , and at 100 s was 5.0 cm 3 . For the in-vivo swine experiments, the average ablation area measured 2.0x0.75 cm with a maximum of 3.5x1.5 cm. CEUS was utilized with the contrast agent Definity (Lantheus) for identification of lacerations as well as immediate post operative evaluation of therapy. CONCLUSION: These experiments demonstrate the feasibility of CEUS guided transdermal HIFU ablation and the time-dependent size of ablation. This work warrants future investigations into using ultrasound to detect active bleeding and HIFU to coagulate grade III and IV liver laceration. STUDY TYPE: Therapeutic/care management.

Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.

Cost-effectiveness analysis of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma.

BACKGROUND: To evaluate the cost-effectiveness of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma (HCC) from the perspective of the Chinese health service system. METHODS: A lifetime partitioned survival model (PSM) was developed to cost-effectively analyze Tislelizumab vs Sorafenib as the first-line treatment of unresectable HCC. The clinical and safety data were derived from a recently randomized clinical trial (RATIONALE-301). Utilities were collected from the published literature. Costs were obtained from an open-access database (http://www.yaozh.com) and previous studies. The model cycle was 21 days, according to the RATIONALE-301 study, and the simulation period was patients' lifetime. Long-term direct medical costs and quality-adjusted life-years (QALYs) were determined. The incremental cost-effectiveness ratio (ICER) was used as the evaluation index. one-way sensitivity analysis (OSWA) and probabilistic sensitivity analysis (PSA) were used to analyze the uncertainty of parameters and to adjust and verify the stability of the baseline results. RESULTS: The Tislelizumab group generated a cost of $39,746.34 and brought health benefits to 2.146 QALYs, while the cost and utility of the Sorafenib group were $26750.95 and 1.578 QALYs, respectively. The Tislelizumab group increased QALYs by 0.568, the incremental cost was $12995.39, and the ICER was $22869.64/QALY, lower than the willingness to pay threshold (WTP). OSWA results showed that the utility of progressed disease (PD), cost of Camrelizumab, and cost of Tislelizumab were the main factors affecting the ICER. PSA results showed that, within 1000 times the Monte Carlo simulation, the cost of the Tislelizumab group was lower than three times the per capita gross domestic product (GDP) of China ($37653/QALY). The cost-effectiveness acceptability curves (CEAC) revealed that when WTP was no less than $12251.00, the Tislelizumab group was the dominant scheme, and the economic advantage grew with an increasing WTP. When WTP ≥ $19000.00, the Tislelizumab group became the absolute economic advantage. CONCLUSION: Under the current economic conditions in China, the Tislelizumab therapeutic scheme is more cost-effective than the Sorafenib therapeutic scheme for treating patients with unresectable HCC.

The power and the promise of synthetic lethality for clinical application in cancer treatment.

Synthetic lethality is a phenomenon wherein the simultaneous deficiency of two or more genes results in cell death, while the deficiency of any individual gene does not lead to cell death. In recent years, synthetic lethality has emerged as a significant topic in the field of targeted cancer therapy, with certain drugs based on this concept exhibiting promising outcomes in clinical trials. Nevertheless, the presence of tumor heterogeneity and the intricate DNA repair mechanisms pose challenges to the effective implementation of synthetic lethality. This review aims to explore the concepts, development, and ethical quandaries surrounding synthetic lethality. Additionally, it will provide an in-depth analysis of the clinical application and underlying mechanism of synthetic lethality.

The power and the promise of CAR-mediated cell immunotherapy for clinical application in pancreatic cancer.

BACKGROUND: Pancreatic cancer, referred to as the "monarch of malignancies," is a neoplastic growth mostly arising from the epithelial cells of the pancreatic duct and acinar cells. This particular neoplasm has a highly unfavorable prognosis due to its marked malignancy, inconspicuous initial manifestation, challenging early detection, rapid advancement, and limited survival duration. Cellular immunotherapy is the ex vivo culture and expansion of immune effector cells, granting them the capacity to selectively target malignant cells using specialized techniques. Subsequently, these modified cells are reintroduced into the patient's organism with the purpose of eradicating tumor cells and providing therapeutic intervention for cancer. PRESENT SITUATION: Presently, the primary cellular therapeutic modalities employed in the treatment of pancreatic cancer encompass CAR T-cell therapy, TCR T-cell therapy, NK-cell therapy, and CAR NK-cell therapy. AIM OF REVIEW: This review provides a concise overview of the mechanisms and primary targets associated with various cell therapies. Additionally, we will explore the prospective outlook of cell therapy in the context of treating pancreatic cancer.

KLK10/LIPH/PARD6B/SLC52A3 are promising molecular biomarkers for the prognosis of pancreatic cancer through a ceRNA network.

Pancreatic adenocarcinoma (PAAD) remains challenging to diagnose and treat clinically due to its difficult early diagnosis, low surgical resection rate, and high risk of postoperative recurrence and metastasis. SMAD4 is a classical mutated gene in pancreatic cancer and is lost in up to 60%-90 % of PAAD patients, and its mutation often predicts a poor prognosis and treatment resistance. In this study, based on the expression profile data in The Cancer Genome Atlas database, we identified a ceRNA network composed of 2 lncRNAs, 1 miRNA, and 4 mRNAs through differential expression analysis and survival prognosis analysis. Among them, high expression of KLK10/LIPH/PARD6B/SLC52A3 influenced the prognosis and overall survival of PAAD patients. We confirmed the high expression of these target genes in pancreatic tissue of pancreatic-specific SMAD4-deficient mice. In addition, immune infiltration analysis showed that the high expression of these target genes affects the tumor immune environment and contributes to the progression of PAAD. Abnormal overexpression of these target genes may be caused by hypermethylation. In conclusion, we found that KLK10/LIPH/PARD6B/SLC52A3 is a potential prognostic marker for PAAD based on a competing endogenous RNA-mediated mechanism and revealed the potential pathogenic mechanism by which deficient expression of SMAD4 promotes pancreatic cancer progression, which provides a new pathway and theoretical basis for targeted therapy or improved prognosis of pancreatic cancer. These data will help reveal potential therapeutic targets for pancreatic cancer and improve the prognosis of pancreatic cancer patients.

Contrast-enhanced US Evaluation of Hepatocellular Carcinoma Response to Chemoembolization: A Prospective Multicenter Trial.

Background Contrast-enhanced (CE) US has been studied for use in the detection of residual viable hepatocellular carcinoma (HCC) after locoregional therapy, but multicenter data are lacking. Purpose To compare two-dimensional (2D) and three-dimensional (3D) CE US diagnostic performance with that of CE MRI or CT, the current clinical standard, in the detection of residual viable HCC after transarterial chemoembolization (TACE) in a prospective multicenter trial. Materials and Methods Participants aged at least 21 years with US-visible HCC scheduled for TACE were consecutively enrolled at one of three participating academic medical centers from May 2016 to March 2022. Each underwent baseline 2D and 3D CE US before TACE, 2D and 3D CE US 1-2 weeks and/or 4-6 weeks after TACE, and CE MRI or CT 4-6 weeks after TACE. CE US and CE MRI or CT were evaluated by three fellowship-trained radiologists for the presence or absence of viable tumors and were compared with reference standards of pathology (18%), angiography on re-treatment after identification of residual disease at 1-2-month follow-up imaging (31%), 4-8-month CE MRI or CT (42%), or short-term (approximately 1-2 months) CE MRI or CT if clinically decompensated and estimated viability was greater than 50% at imaging (9%). Diagnostic performance criteria, including sensitivity and specificity, were obtained for each modality and time point with generalized estimating equation analysis. Results A total of 132 participants were included (mean age, 64 years ± 7 [SD], 87 male). Sensitivity of 2D CE US 4-6 weeks after TACE was 91% (95% CI: 84, 95), which was higher than that of CE MRI or CT (68%; 95% CI: 58, 76; P < .001). Sensitivity of 3D CE US 4-6 weeks after TACE was 89% (95% CI: 81, 94), which was higher than that of CE MRI or CT (P < .001), with no evidence of a difference from 2D CE US (P = .22). CE MRI or CT had 85% (95% CI: 76, 91) specificity, higher than that of 4-6-week 2D and 3D CE US (70% [95% CI: 56, 80] and 67% [95% CI: 53, 78], respectively; P = .046 and P = .023, respectively). No evidence of differences in any diagnostic criteria were observed between 1-2-week and 4-6-week 2D CE US (P > .21). Conclusion The 2D and 3D CE US examinations 4-6 weeks after TACE revealed higher sensitivity in the detection of residual HCC than CE MRI or CT, albeit with lower specificity. Importantly, CE US performance was independent of follow-up time. Clinical trial registration no. NCT02764801 © RSNA, 2023 Supplemental material is available for this article.

Identification of sentinel lymph nodes in esophageal cancer patients using contrast-enhanced EUS with peritumoral injections.

Objectives: The objective of this pilot study was to compare the performance of contrast-enhanced EUS (CE-EUS)-guided fine-needle aspiration (FNA) with EUS-FNA for lymph node (LN) staging in esophageal cancer. Methods: Thirty-seven subjects with esophageal cancer undergoing EUS staging were enrolled, and 30 completed this institutional review board-approved study. A Prosound F75 US system (Hitachi Medical Systems, Tokyo, Japan) with harmonic contrast imaging software and GF-UCT180 curvilinear endoscope (Olympus, Tokyo, Japan) was utilized. All LNs identified by standard EUS were first noted. Sonazoid (dose: 1 mL; GE Healthcare, Oslo, Norway) was administered peritumorally, and all enhanced LNs were recorded. Fine-needle aspiration was performed on LNs considered suspicious by EUS alone, as well as LNs enhanced on CE-EUS. Performance of each modality was compared using FNA cytology as reference standard. Results: A total of 132 LNs were detected with EUS, of which 59 showed enhancement on CE-EUS. Fifty-three LNs underwent FNA, and 22 LNs were determined to be malignant. Among the latter, 10 were considered suspicious by EUS, whereas the other 12 LNs underwent FNA only because of CE-EUS enhancement. Contrast-enhanced EUS showed enhancement in 19 of the 22 malignant LNs. The rate of metastatic node identification from EUS was 45% (10/22), and it was 86% (19/22; P = 0.008) for CE-EUS. Eight subjects (8/30 [27% of study total]) had nodal status upgraded by the addition of CE-EUS, which influenced LN staging and clinical management. Conclusions: Fine-needle aspiration of LNs identified by CE-EUS may increase metastasis positive rate by ruling out LNs not associated with the tumor drainage pattern. In addition, CE-EUS seems to identify more metastatic LNs that would not be biopsied under the standard EUS criteria.

Surmounting Cancer Drug Resistance: New Perspective on RNA-Binding Proteins.

RNA-binding proteins (RBPs), being pivotal elements in both physiological and pathological processes, possess the ability to directly impact RNA, thereby exerting a profound influence on cellular life. Furthermore, the dysregulation of RBPs not only induces alterations in the expression levels of genes associated with cancer but also impairs the occurrence of post-transcriptional regulatory mechanisms. Consequently, these circumstances can give rise to aberrations in cellular processes, ultimately resulting in alterations within the proteome. An aberrant proteome can disrupt the equilibrium between oncogenes and tumor suppressor genes, promoting cancer progression. Given their significant role in modulating gene expression and post-transcriptional regulation, directing therapeutic interventions towards RBPs represents a viable strategy for combating drug resistance in cancer treatment. RBPs possess significant potential as diagnostic and prognostic markers for diverse cancer types. Gaining comprehensive insights into the structure and functionality of RBPs, along with delving deeper into the molecular mechanisms underlying RBPs in tumor drug resistance, can enhance cancer treatment strategies and augment the prognostic outcomes for individuals afflicted with cancer.

Mendelian randomization analysis identified tumor necrosis factor as being associated with severe COVID-19.

Background: Observational studies have shown that anti-tumor necrosis factor (TNF) therapy may be beneficial for patients with coronavirus disease 2019 (COVID-19). Nevertheless, because of the methodological restrictions of traditional observational studies, it is a challenge to make causal inferences. This study involved a two-sample Mendelian randomization analysis to investigate the causal link between nine TNFs and COVID-19 severity using publicly released genome-wide association study summary statistics. Methods: Summary statistics for nine TNFs (21,758 cases) were obtained from a large-scale genome-wide association study. Correlation data between single-nucleotide polymorphisms and severe COVID-19 (18,152 cases vs. 1,145,546 controls) were collected from the COVID-19 host genetics initiative. The causal estimate was calculated by inverse variance-weighted (IVW), MR-Egger, and weighted median methods. Sensitivity tests were conducted to assess the validity of the causal relationship. Results: Genetically predicted TNF receptor superfamily member 6 (FAS) positively correlated with the severity of COVID-19 (IVW, odds ratio = 1.10, 95% confidence interval = 1.01-1.19, p = 0.026), whereas TNF receptor superfamily member 5 (CD40) was protective against severe COVID-19 (IVW, odds ratio = 0.92, 95% confidence interval = 0.87-0.97, p = 0.002). Conclusion: Genetic evidence from this study supports that the increased expression of FAS is associated with the risk of severe COVID-19 and that CD40 may have a potential protective effect against COVID-19.

Anatomy Versus Physiology: Is Breast Lymphatic Drainage to the Internal Thoracic (Internal Mammary) Lymphatic System Clinically Relevant?

Approximately 15%-25% of breast lymphatic drainage passes through the internal thoracic (internal mammary) lymphatic system, draining the inner quadrants of the breast. This study aimed to use lymphosonography to identify sentinel lymph nodes (SLNs) in the axillary and internal thoracic lymphatic systems in patients with breast cancer. Seventy-nine patients received subcutaneous ultrasound contrast agent injections around the tumor. Lymphosonography was used to identify SLNs. In 14 of the 79 patients (17.7%), the tumor was located in the inner quadrant of the breast. Lymphosonography identified 217 SLNs in 79 patients, averaging 2.7 SLNs per patient. The 217 identified SLNs in the 79 patients were located in the axillary lymphatic system; none were located in the internal thoracic (internal mammary) lymphatic system, although it was expected in two to four patients (i.e., 4-11 SLNs). These results implied that SLNs associated with breast cancer are predominantly located in the axillary lymphatic system.

Whole-exome and targeted gene sequencing of large-cell lung carcinoma reveals recurrent mutations in the PI3K pathway.

BACKGROUND: Large cell lung carcinoma (LCLC) is an exceptionally aggressive disease with a poor prognosis. At present, little is known about the molecular pathology of LCLC. METHODS: Ultra-deep sequencing of cancer-related genes and exome sequencing were used to detect the LCLC mutational in 118 tumor-normal pairs. The cell function test was employed to confirm the potential carcinogenic mutation of PI3K pathway. RESULTS: The mutation pattern is determined by the predominance of A > C mutations. Genes with a significant non-silent mutation frequency (FDR) < 0.05) include TP53 (47.5%), EGFR (13.6%) and PTEN (12.1%). Moreover, PI3K signaling (including EGFR, FGRG4, ITGA1, ITGA5, and ITGA2B) is the most mutated pathway, influencing 61.9% (73/118) of the LCLC samples. The cell function test confirmed that the potential carcinogenic mutation of PI3K pathway had a more malignant cell function phenotype. Multivariate analysis further revealed that patients with the PI3K signaling pathway mutations have a poor prognosis (P = 0.007). CONCLUSIONS: These results initially identified frequent mutation of PI3K signaling pathways in LCLC and indicate potential targets for the treatment of this fatal type of LCLC.

Improved Tumor Control Following Radiosensitization with Ultrasound-Sensitive Oxygen Microbubbles and Tumor Mitochondrial Respiration Inhibitors in a Preclinical Model of Head and Neck Cancer.

Tumor hypoxia (oxygen deficiency) is a major contributor to radiotherapy resistance. Ultrasound-sensitive microbubbles containing oxygen have been explored as a mechanism for overcoming tumor hypoxia locally prior to radiotherapy. Previously, our group demonstrated the ability to encapsulate and deliver a pharmacological inhibitor of tumor mitochondrial respiration (lonidamine (LND)), which resulted in ultrasound-sensitive microbubbles loaded with O2 and LND providing prolonged oxygenation relative to oxygenated microbubbles alone. This follow-up study aimed to evaluate the therapeutic response to radiation following the administration of oxygen microbubbles combined with tumor mitochondrial respiration inhibitors in a head and neck squamous cell carcinoma (HNSCC) tumor model. The influences of different radiation dose rates and treatment combinations were also explored. The results demonstrated that the co-delivery of O2 and LND successfully sensitized HNSCC tumors to radiation, and this was also enhanced with oral metformin, significantly slowing tumor growth relative to unsensitized controls (p < 0.01). Microbubble sensitization was also shown to improve overall animal survival. Importantly, effects were found to be radiation dose-rate-dependent, reflecting the transient nature of tumor oxygenation.

Myricetin-induced suicidal erythrocyte death.

BACKGROUND: Myricetin, a type of flavonol commonly found in fruits and herbs, has demonstrated anticancer properties by triggering the process of apoptosis or programmed cell death in tumor cells. Despite the absence of mitochondria and nuclei, erythrocytes can undergo programmed cell death, also known as eryptosis.This process is characterized by cell shrinkage, externalization of phosphatidylserine (PS) on the cell membrane, and the formation of membrane blebs. The signaling of eryptosis involves Ca2+ influx, the formation of reactive oxygen species (ROS), and the accumulation of cell surface ceramide. The present study explored the effects of myricetin on eryptosis. METHODS AND RESULTS: Human erythrocytes were exposed to various concentrations of myricetin (2-8 µM) for 24 h. Flow cytometry was used to assess the markers of eryptosis, including PS exposure, cellular volume, cytosolic Ca2+ concentration, and ceramide accumulation. In addition, the levels of intracellular ROS were measured using the 2',7'-dichlorofluorescin diacetate (DCFDA) assay. The myricetin-treated (8 µM) erythrocytes significantly increased Annexin-positive cells, Fluo-3 fluorescence intensity, DCF fluorescence intensity, and the accumulation of ceramide. The impact of myricetin on the binding of annexin-V was significantly reduced, but not completely eliminated, by the nominal removal of extracellular Ca2+. CONCLUSION: Myricetin triggers eryptosis, which is accompanied and, at least in part, caused by Ca2+ influx, oxidative stress and increase of ceramide abundance.

Ultrasound-Based Machine Learning Approach for Detection of Nonalcoholic Fatty Liver Disease.

OBJECTIVES: Current diagnosis of nonalcoholic fatty liver disease (NAFLD) relies on biopsy or MR-based fat quantification. This prospective study explored the use of ultrasound with artificial intelligence for the detection of NAFLD. METHODS: One hundred and twenty subjects with clinical suspicion of NAFLD and 10 healthy volunteers consented to participate in this institutional review board-approved study. Subjects were categorized as NAFLD and non-NAFLD according to MR proton density fat fraction (PDFF) findings. Ultrasound images from 10 different locations in the right and left hepatic lobes were collected following a standard protocol. MRI-based liver fat quantification was used as the reference standard with >6.4% indicative of NAFLD. A supervised machine learning model was developed for assessment of NAFLD. To validate model performance, a balanced testing dataset of 24 subjects was used. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy with 95% confidence interval were calculated. RESULTS: A total of 1119 images from 106 participants was used for model development. The internal evaluation achieved an average precision of 0.941, recall of 88.2%, and precision of 89.0%. In the testing set AutoML achieved a sensitivity of 72.2% (63.1%-80.1%), specificity of 94.6% (88.7%-98.0%), positive predictive value (PPV) of 93.1% (86.0%-96.7%), negative predictive value of 77.3% (71.6%-82.1%), and accuracy of 83.4% (77.9%-88.0%). The average agreement for an individual subject was 92%. CONCLUSIONS: An ultrasound-based machine learning model for identification of NAFLD showed high specificity and PPV in this prospective trial. This approach may in the future be used as an inexpensive and noninvasive screening tool for identifying NAFLD in high-risk patients.

Sentinel Lymph Node Identification in Post Neoadjuvant Chemotherapy Breast Cancer Patients Undergoing Surgical Excision Using Lymphosonography.

OBJECTIVES: This study evaluated the efficacy of lymphosonography in the identification of sentinel lymph nodes (SLNs) in post neoadjuvant chemotherapy patients with breast cancer scheduled to undergo surgical excision. METHODS: Seventy-nine subjects scheduled for breast cancer surgery with SLN excision completed this IRB-approved study, out of which 18 (23%) underwent neoadjuvant chemotherapy before surgery. Subjects underwent percutaneous Sonazoid (GE Healthcare) injections around the tumor area for a total of 1.0 mL. Lymphosonography was performed using CPS on an S3000 HELX scanner (Siemens Healthineers) with a linear probe. Subjects received blue dye and radioactive tracer as part of their standard of care. Excised SLNs were classified as positive or negative for the presence of blue dye, radioactive tracer and Sonazoid. The results were compared between methods and pathology findings. RESULTS: Seventy-two SLNs were surgically excised from 18 subjects, 29 were positive for blue dye, 63 were positive for radioactive tracer and 57 were positive for Sonazoid. Comparison with blue dye showed that both radioactive tracer and lymphosonography achieved an accuracy of 53% (P > .50). Comparison with radioactive tracer showed that blue dye had an accuracy of 53%, while lymphosonography achieved an accuracy of 67% (P < .01). Of the 72 SLNs, 15 were determined malignant by pathology; the detection rate was 47% for blue dye (7/15), 67% for radioactive tracer (10/15) and 100% for lymphosonography (15/15) (P < .001). CONCLUSIONS: Lymphosonography achieved similar accuracy as radioactive tracer and higher accuracy than blue dye for identifying SLNs. The 15 SLNs positive for malignancy were all identified by lymphosonography.

Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinoma.

BACKGROUND: Aberrations in MYC underlie a large proportion of liver hepatocellular carcinoma (LIHC) cases; however, MYC is difficult to target because of its undruggable structure. We aimed to uncover MYC-associated molecular targets to provide new strategies for LIHC treatment. METHODS: LIHC transcriptome datasets and clinical information were obtained from The Cancer Genome Atlas. A series of bioinformatics analyses were performed for 370 patients who were stratified based on the median MYC expression level (high-MYC group and low-MYC group). Correlation analysis was performed to determine relationships between the expression of key MYC-associated genes and prognosis, DNA promotor methylation, and immune cell infiltration. Gene ontology and Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analyses were performed to elucidate the functions of these genes in LIHC. Their expression and functions in LIHC were further verified using transgenic mice overexpressing c-Myc under control of the hepatocyte-specific promoter (Alb-Cre). RESULTS: AURKB, CCNB2, and CDKN3 were overexpressed in LIHC patients with high MYC expression and were associated with poor prognosis. Upregulation of these 3 genes was significantly correlated with hypomethylated promoter status, advanced T stage, metastasis, and immune cell infiltration in LIHC patients. Functional enrichment analyses indicated that these genes participate in the "p53 signaling pathway" and "cell cycle". Furthermore, RT-PCR and IHC analysis revealed that their mRNA and protein expression levels were upregulated in an Alb-Cre;cMYClsl/- mouse model. Drugs that target these 3 MYC-related genes were identified. CONCLUSION: Taken together, our results identify biomarkers of potential utility for managing liver cancer therapy owing to their significance in tumorigenesis, proliferation, and tumor immunity.

Sentinel Lymph Node Identification in Patients With Breast Cancer Using Lymphosonography.

The objective of the work described here was to evaluate the efficacy of lymphosonography in identifying sentinel lymph nodes (SLNs) in patients with breast cancer undergoing surgical excision. Of the 86 individuals enrolled, 79 completed this institutional review board-approved study. Participants received subcutaneous 1.0-mL injections of ultrasound contrast agent (UCA) around the tumor. An ultrasound scanner with contrast-enhanced ultrasound (CEUS) capabilities was used to identify SLNs. Participants were administered with blue dye and radioactive tracer to guide SLN excision as standard-of-care. Excised SLNs were classified as positive or negative for the presence of blue dye, radioactive tracer and UCA, and sent for pathology. Two hundred fifty-two SLNs were excised; 158 were positive for blue dye, 222 were positive for radioactive tracer and 223 were positive for UCA. Comparison with blue dye revealed accuracies of 96.2% for radioactive tracer and 99.4% for lymphosonography (p > 0.15). Relative to radioactive tracer, blue dye had an accuracy of 68.5%, and lymphosonography achieved 86.5% (p < 0.0001). Of 252 SLNs excised, 34 were determined to be malignant by pathology; 18 were positive for blue dye (detection rate = 53%), 23 for radioactive tracer (detection rate = 68%) and 34 for UCA (detection rate = 100%) (p < 0.0001). Lymphosonography was similar in accuracy to radioactive tracer and higher in accuracy than blue dye in identifying SLNs. All 34 malignant SLNs were identified by lymphosonography.

Volumetric Quantitative Contrast-enhanced Ultrasonography Evaluation of Complex Renal Cysts: An Adjunctive Metric to the Bosniak Classification System to Predict Malignancy.

BACKGROUND: Management of complex renal cysts is guided by the Bosniak classification system, which may be inadequate for risk stratification of patients for intervention. Fractional tumor vascularity (FV) calculated from volumetric contrast-enhanced ultrasound (CEUS) images may provide additional useful information. OBJECTIVE: To evaluate CEUS and FV calculation for risk stratification of patients with complex renal cysts. DESIGN, SETTING, AND PARTICIPANTS: This was a pilot prospective study with institutional review board approval involving patients undergoing surgery for Bosniak IIF-IV complex renal cysts. CEUS was performed preoperatively on the day of surgery with two-dimensional (2D) and three-dimensional (3D) imaging and sulfur hexafluoride lipid-type A microspheres as the ultrasound contrast agent. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A custom MATLAB program was used to select regions of interest on CEUS scans. FV was calculated according to FV = 1 - (total nonenhancing area/total lesion area). We assessed the ability of 2D- and 3D-derived percentage FV (2DFV%, and 3DFV%) and Bosniak classification schemes (pre-2019 [P2019B] and post-2019 [B2019]) to predict malignancy, aggressive histology, and upstaging on surgical pathology. Performance was assessed as area under the receiver operating characteristic curve (AUC). RESULTS AND LIMITATIONS: Twenty eligible patients were included in final analysis, of whom 85% (n = 17) had Bosniak IV cysts and 85% (n = 17) had malignant disease on final pathology. Four (24%) of the malignant lesions were International Society of Urological Pathology grade 3-4. The AUC for predicting malignancy was 0.980, 0.824, 0.863, and 0.824 with P2019B, B2019, 2DFV%, and 3DFV%, respectively. When the Bosniak classification was combined with FV%, three models had an AUC of 1, while the combined 2DFV% + B2019 model had AUC of 0.980. CONCLUSIONS: FV is a novel metric for evaluating complex cystic renal masses and enhances the ability of the Bosniak classification system to predict malignancy. This metric may serve as an adjunct in risk stratification for surgical intervention. Further prospective evaluation is warranted. PATIENT SUMMARY: Cysts in the kidney are currently classified using a scheme called the Bosniak system. We assessed measurement of the percentage of vascular tissue (called fractional vascularity) in cysts on a special type of ultrasound scan. This promising test adds information when combined with the Bosniak system and can help in guiding appropriate treatment.