Identification of a cancer-associated fibroblast classifier for predicting prognosis and therapeutic response in lung squamous cell carcinoma.

Reliable prognostic gene signatures for cancer-associated fibroblasts (CAFs) in lung squamous cell carcinoma (LUSC) are still lacking, and the underlying genetic principles remain unclear. Therefore, the 2 main aims of our study were to establish a reliable CAFs prognostic gene signature that can be used to stratify patients with LUSC and to identify promising potential targets for more effective and individualized therapies. Clinical information and mRNA expression were accessed of the cancer genome atlas-LUSC cohort (n = 501) and GSE157011 cohort (n = 484). CAFs abundance were quantified by the multi-estimated algorithms. Stromal CAF-related genes were identified by weighted gene co-expression network analysis. The least absolute shrinkage and selection operator Cox regression method was utilized to identify the most relevant CAFs candidates for predicting prognosis. Chemotherapy sensitivity scores were calculated using the "pRRophetic" package in R software, and the tumor immune dysfunction and exclusion algorithm was employed to evaluate immunotherapy response. Gene set enrichment analysis and the Search Tool for Interaction of Chemicals database were applied to clarify the molecular mechanisms. In this study, we identified 288 hub CAF-related candidate genes by weighted gene co-expression network analysis. Next, 34 potential prognostic CAFs candidate genes were identified by univariate Cox regression in the cancer genome atlas-LUSC cohort. We prioritized the top 8 CAFs prognostic genes (DCBLD1, SLC24A3, ILK, SMAD7, SERPINE1, SNX9, PDGFA, and KLF10) by a least absolute shrinkage and selection operator Cox regression model, and these genes were used to identify low- and high-risk subgroups for unfavorable survival. In silico drug screening identified 6 effective compounds for high-risk CAFs-related LUSC: TAK-715, GW 441756, OSU-03012, MP470, FH535, and KIN001-266. Additionally, search tool for interaction of chemicals database highlighted PI3K-Akt signaling as a potential target pathway for high-risk CAFs-related LUSC. Overall, our findings provide a molecular classifier for high-risk CAFs-related LUSC and suggest that treatment with PI3K-Akt signaling inhibitors could benefit these patients.

Calcifying epithelioma of malherbe (Pilomatrixoma): Clinical and sonographic features.

PURPOSE: The purpose of this study was to describe the clinical and sonographic features of calcifying epitheliomas (pilomatrixomas). METHODS: We retrospectively reviewed the clinical data and sonographic appearances of 59 cases of calcifying epitheliomas in 58 patients that were confirmed pathologically. RESULTS: The mean age of the patients was 26 years (range, 5-69 years) and the female-to-male ratio was 1.2. All masses were located in subcutaneous soft tissues. Overall, 76.3% of the cases were located in the head and neck; the mean tumor size was 13 mm, and 72.9% of the cases were between 10 and 20 mm in size. Of the lesions, 62.7% were hypoechoic masses with internal calcifications, and 74.6% of them showed low or moderate internal vascularity on Doppler imaging. CONCLUSIONS: The diagnosis of calcifying epithelioma should be considered in a patient with a painless, circumscribed, oval-shaped hypoechoic mass with internal calcifications and internal vascularity in the subcutaneous soft tissues of the head or neck. The mass may be small and have well-defined margins, with hypoechogenicity. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:3-7, 2018.

Clinical utility of endoscopic ultrasound elastography for identification of malignant pancreatic masses: a meta-analysis.

BACKGROUND AND AIM: Endoscopic ultrasound (EUS) elastography is not used for detection but rather for characterization of solid pancreatic masses. A meta-analysis was used to assess the accuracy of EUS elastography for identification of malignant pancreatic masses. METHODS: PubMed, the Cochrane Library, and the ISI Web of Knowledge were searched. The studies relating to evaluation accuracy of qualitative or quantitative EUS elastography for identification of malignant pancreatic masses were collected. Language was limited to English. The sensitivity and specificity were used to examine the accuracy. Clinical utility was evaluated by likelihood ratio scattergram. RESULTS: A total of 10 studies including 893 pancreatic masses (646 malignant, 72.3%) were analyzed. The summary sensitivity and specificity for the diagnosis of malignant pancreatic masses were 0.98 (95% confidence interval [CI] 0.93-1.00) and 0.69 (95% CI 0.52-0.82) for qualitative EUS elastography, and 0.96 (95% CI 0.86-0.99) and 0.76 (95% CI 0.58-0.87) for quantitative EUS elastography, respectively. The hierarchical summary receiver operating characteristic curves were 0.94 and 0.93 for qualitative and quantitative EUS elastography. The accuracy of quantitative methods was similar to qualitative methods. The positive and negative likelihood ratios were 3.15 and 0.03 for qualitative EUS elastography, and 3.94 and 0.05 for quantitative EUS elastography, respectively. Both qualitative and quantitative methods were useful for exclusion of presence of malignant pancreatic masses and not for its confirmation. CONCLUSIONS: EUS elastography could be used as a good identification tool for benign and malignant pancreatic masses, with its good performance for exclusion of presence of malignant pancreatic masses.

Clinical utility of acoustic radiation force impulse imaging for identification of malignant liver lesions: a meta-analysis.

OBJECTIVES: To assess the performance of acoustic radiation force impulse (ARFI) imaging for identification of malignant liver lesions using meta-analysis. METHODS: PubMed, the Cochrane Library, the ISI Web of Knowledge and the China National Knowledge Infrastructure were searched. The studies published in English or Chinese relating to evaluation accuracy of ARFI imaging for identification of malignant liver lesions were collected. A hierarchical summary receiver operating characteristic (HSROC) curve was used to examine the ARFI imaging accuracy. Clinical utility of ARFI imaging for identification of malignant liver lesions was evaluated by Fagan plot analysis. RESULTS: A total of eight studies which included 590 liver lesions were analysed. The summary sensitivity and specificity for identification of malignant liver lesions were 0.86 (95 % confidence interval (CI) 0.74-0.93) and 0.89 (95 % CI 0.81-0.94), respectively. The HSROC was 0.94 (95 % CI 0.91-0.96). After ARFI imaging results over the cut-off value for malignant liver lesions ("positive" result), the corresponding post-test probability for the presence (if pre-test probability was 50 %) was 89 %; in "negative" measurement, the post-test probability was 13 %. CONCLUSIONS: ARFI imaging has a high accuracy in the classification of liver lesions. KEY POINTS: Acoustic radiation force impulse (ARFI) imaging is a novel ultrasound-based elastography method. This study comprehensively assessed the published performance of ARFI for liver lesions. ARFI imaging appears to have high sensitivity and specificity for liver lesions. ARFI can help differentiate liver lesions and may prevent unnecessary biopsies.

Performance of platelet count/spleen diameter ratio for diagnosis of esophageal varices in cirrhosis: a meta-analysis.

BACKGROUND: Platelet count/spleen diameter ratio (PSR) is a non-invasive method for the assessment of esophageal varices (EV), developed as an alternative to endoscopy. AIM: To assess the performance of PSR for diagnosis of EV using meta-analysis. METHODS: PubMed, EMBASE, the Cochrane Library, ISI web of Knowledge, China National Knowledge Infrastructure, and article references were searched. We included studies using endoscopy as a reference standard, with the data necessary to calculate the true and false positive, true and false negative diagnostic results of PSR for EV. The quality of the studies was rated with the QUADAS tool. The hierarchical summary receiver operating characteristic (HSROC) was used to examine the PSR accuracy for the diagnosis of EV. Heterogeneity was explored using meta-regression. Clinical utility of PSR for EV was evaluated by a Fagan plot. RESULTS: In 20 studies (n = 3,063), the HSROC of the PSR for EV was 0.95 at various thresholds. At the threshold of 909, the summary sensitivities and specificities were 0.92 (95% CI, 0.79-0.97) and 0.87 (95% CI, 0.76-0.93), respectively. The HSROC was also 0.95 at the threshold of 909. If PSR was below 909 for EV ("positive" result), the post-test probability (if pre-test probability was 50%) was 87%, while if PSR was at or over 909 ("negative" result), the post-test probability was only 9%. PSR also had a high accuracy in diagnosis of EV in patients with compensated cirrhosis. CONCLUSIONS: PSR can identify EV in cirrhosis with a high accuracy. Application of this index may decrease the need for endoscopy among cirrhotic patients.

Real-time elastography for the differentiation of benign and malignant superficial lymph nodes: a meta-analysis.

BACKGROUND: Real-time elastography (RTE), as a non-invasive method, is used for the classification of benign and malignant lymph nodes (LNs) and developed as an alternative to biopsy. Elasticity score (ES) and strain ratio (SR) are used for the interpretation of RTE. We studied the performance of RTE for diagnosis of malignant LNs using meta-analysis. METHODS: PubMed, the Cochrane Library, ISI Web of Knowledge, China National Knowledge Infrastructure were searched. The studies published in English or Chinese relating to the diagnostic value of RTE for superficial LNs were collected. Hierarchical summary receiver operating characteristic (HSROC) curve was used to examine the RTE accuracy. Clinical utility of RTE for LNs was evaluated by Fagan plot analysis. RESULTS: A total of 9 studies which included 835 LNs were analyzed. The summary sensitivity and specificity for the diagnosis of malignant LNs were 0.74 (95% confidence interval (CI), 0.66-0.81) and 0.90 (95% CI, 0.82-0.94) for ES, and 0.88 (95% CI, 0.79-0.93) and 0.81 (95% CI, 0.49-0.95) for SR, respectively. Compared to ES, SR obviously improved the diagnostic sensitivity value. The HSROCs were 0.88 for ES and 0.91 for SR, respectively. After RTE results over the cut-off value for malignant LNs ("positive" result), the corresponding post-test probability for the presence (if pre-test probability was 50%) was 88% for ES and 82% for SR, respectively; while, in "negative" measurement, the post-test probability was 22% and 13%, respectively. CONCLUSION: RTE has a high accuracy in the classification of superficial LNs and can potentially help to select suspicious LNs for biopsy.