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The forkhead box O (FOXO) transcription factors (TFs) family are frequently mutated, deleted, or amplified in various human cancers, making them attractive candidates for therapy. However, their roles in pan-cancer remain unclear. Here, we evaluated the expression, prognostic value, mutation, methylation, and clinical features of four FOXO family genes (FOXO1, FOXO3, FOXO4, and FOXO6) in 33 types of cancers based on the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases. We used a single sample gene set enrichment analysis (ssGSEA) algorithm to establish a novel index called “FOXOs score”. Moreover, we investigated the association between the FOXOs score and tumor microenvironment (TME), the responses to multiple treatments, along with drug resistance. We found that the FOXO family genes participated in tumor progression and were related to the prognosis in various types of cancer. We calculated the FOXOs score and found that it was significantly correlated with multiple malignant pathways in pan-cancer, including Wnt/beta-catenin signaling, TGF-beta signaling, and hedgehog signaling. In addition, the FOXOs score was also associated with multiple immune-related characteristics. Furthermore, the FOXOs score was sensitive for predicting the efficacy of diverse treatments in multiple cancers, especially immunotherapy. In conclusion, FOXO family genes were vital in pan-cancer and were strongly correlated with the TME. A high FOXOs score indicated an excellent immune-activated TME and sensitivity to multiple treatments. Hence, the FOXOs score might potentially be used as a biomarker in patients with a tumor.

Aims With prevalence of hepatocellular carcinoma (HCC) in low-risk population (LRP), establishing a non-invasive diagnostic strategy becomes increasingly urgent to spare unnecessary biopsies in this population. The purposes of this study were to find characterisics of HCC and to establish a proper non-invasive method to diagnose HCC in LRP. Methods A total of 681 patients in LRP (defined as the population without cirrhosis, chronic HBV infection or HCC history) were collected from 2 institutions. The images of computed tomography (CT) and magnetic resonance imaging (MRI) were manually analysed. We divided the patients into the training cohort (n = 324) and the internal validating cohort (n = 139) by admission time in the first institution. The cohort in the second institution was viewed as the external validation (n = 218). A multivariate logistic regression model incorporating both imaging and clinical independent risk predictors was developed. C-statistics was used to evaluate the diagnostic performance. Results Besides the major imaging features of HCC (non-rim enhancement, washout and enhancing capsule), tumor necrosis or severe ischemia (TNSI) on imaging and two clinical characteristics (gender and alpha fetoprotein) were also independently associated with HCC diagnosis (all P Conclusions The clinical model in this study developed a satisfied non-invasive diagnostic performance for HCC in LRP.

Background To determine whether ultrasound elastography can distinguish reactive or metastatic small lymph nodes (sLN) of magnetic resonance imaging (MRI) staged cervical N0 patients with nasopharyngeal carcinoma (NPC). Methods A pilot study was performed involving the diagnostic performances of conventional high-frequency ultrasound (CHFU) and/or shear wave elastography (SWE) for predicting metastases in sLN of MRI-staged N0 NPC patients with reference to the histologically-proven ultrasound guided core needle biopsy (US-CNB). The diagnosis of CHFU was based on the superficial lymph node ultrasonic criteria with the five-point-scale (FPS). The mean (Emean), minimum (Emin) and maximum (Emax) of the elasticity indices were measured by SWE at the stiffest part of the sLN in kilopascal. Diagnostic performances were analyzed using a receiver operating curve (ROC) on a per-node basis. The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (http://www.researchdata.org.cn), with the approval RDD number as RDDA2017000447. Results All 113 cervical sLN of 49 MRI-staged cervical N0 NPC patients underwent evaluation of CHFU and SWE; 38 sLN (FPS

Diagnostic performances of Five-Point-Scale scores for characterizing cervical small lymph node metastasis at different cut-off point. The diagnostic performances of Five-Point-Scale scores for characterizing cervical sLN at different cut-off point showed the optimal cut-off point was at 3 (=2 vsâ >â 2). (DOCX 15 kb)

We sought to combine the Valsalva maneuver with MRI to evaluate eustachian tube function in patients with nasopharyngeal carcinoma (NPC) and to correlate the extent of tumor invasion with the presence of middle ear effusion (MEE) and eustachian tube dysfunction (ETD).We performed MRI along the lengths of the eustachian tubes, before and after the Valsalva maneuver was performed, in 53 patients with untreated NPC. The images were reviewed by two radiologists.A total of 106 eustachian tubes and middle ears were studied. There was dysfunction in 37 eustachian tubes, which was always ipsilateral to the NPC. There was MEE in 26 ears of 22 patients. In all cases of MEE, there was ipsilateral ETD. ETD was correlated with tumor invasion of the ipsilateral pharyngeal recess (p0.001), pharyngeal opening of the eustachian tube (p0.001), the cartilaginous eustachian tube (p0.001), the eustachian cartilage (p0.001), Ostmann fat pad (p0.001), the levator veli palatine muscle (p0.001), and the tensor veli palatine muscle (p0.001). There was a strong correlation between the grade of parapharyngeal space invasion and ETD (r = 0.809; p0.001) and MEE (r = 0.693; p0.001).Combining the Valsalva maneuver with MRI is helpful in assessing the function of the eustachian tube in patients with NPC. The cause of MEE in patients with NPC is dysfunction of the eustachian tube opening, which is associated with tumor invasion around the eustachian tube.

Purpose To analyze the clinical implications of metastatic cervical lymph nodes in unresectable thoracic esophageal squamous cell carcinoma (SCC) after concurrent chemoradiotherapy (CRT). Methods and materials 208 thoracic esophageal SCC patients treated with concurrent CRT were analyzed retrospectively. Patients were divided into 3 groups according to different status of metastatic cervical lymph nodes: 1. CLN(-), no evidence of metastatic cervical lymph nodes; 2. CPLN(+), evidence of enlarged cervical paraesophageal lymph node without any other metastatic cervical lymph nodes; 3. OCLN(+), any other situations of enlarged cervical lymph nodes. The prognostic factors were examined univariately, then selected for inclusion in a multivariate Cox regression model. Results Three-year OS of CLN(−),CPLN(+), and OCLN(+) groups were 39%, 33%, and 15% (logrank p =0.001). On univariate analysis, variables significantly associated with OS included sex, primary esophageal tumor location, length and cervical nodal disease. On multivariate analysis, primary tumor location (HR1.5, 95%CI 1.1–1.9, p =0.005), tumor length (HR1.5, 95%CI 1.1–2.0, p =0.010) and cervical nodal disease (HR1.2, 95%CI 1.0–1.5, p =0.014) were prognostic factors on OS. Conclusions (1) Primary tumor location, tumor length, and cervical nodal disease were significant prognostic factors on OS in esophageal SCC patients. (2) Patients with CPLN(+) disease tended to have a potential better long-term survival than those with OCLN(+) disease, and metastatic CPLN could be considered as local disease. The survival benefit in CPLN(+) subgroup might be contributed by the patients who presented with upper third thoracic tumors and shorter tumor length. Further investigation is needed.

The aim of this study is to discover regional invasion routes for nasopharyngeal adenoid cystic carcinoma (NACC) through analyses of the magnetic resonance (MR) images and comparison with keratinizing squamous cell carcinoma (KSCC). Both MR results and clinical records were retrospectively reviewed for 18 patients with NACC and 182 patients with KSCC. The metastasis routes of NACC were identified by analysis of MR images of patients who underwent magnetic resonance imaging (MRI). There were significant differences in skull base invasion and cavernous sinus invasion (p = 0.020 and 0.028, respectively) while parapharyngeal space invasion rate was not. The laryngopharynx invasion rate and external pterygoid muscle invasion rate were higher in NACC patients than that in KSCC patients (16.7% vs. 0.5 %, p = 0.002; 27.8% vs. 11.0%, p = 0.040, respectively). Paralysis of the cranial nerves had a significant higher incidence in the NACC group compared to the KSCC group (66.7% vs. 8.2%, p < 0.001). There was significant difference in invasion to the neural foramen between the NACC and KSCC groups (66.7% vs. 36.3%, p = 0.020). Foramen ovale was a common invasion site, significantly higher in NACC patients than in KSCC patients (50.0% vs. 24.1%, p = 0.018). Based on the MRI findings, a regional invasion model of NACC with two possible routes has been built, including aggressive local infiltration along submucosa to laryngopharynx or external pterygoid muscle, and extension from pharyngonasal cavity, through cranial nerve canal to cavernous sinus. The significant difference in overall survival (OS) time between the two different invasion routs and the recurrent rates in different regions also supported the validity of the invasion model.

Purpose The aim of the study was to describe the clinical and computed tomography (CT) findings of primary lymphoepithelioma-like carcinoma (LELC) of the lung. Materials and methods The clinical data and CT findings of 35 patients with histologically proven primary LELC of the lung were retrospectively reviewed. The clinical data included age, sex, smoking history, signs and symptoms, tumor location, tumor size, stage, Epstein-Barr virus (EBV)-encoded small nuclear RNA status, treatment, and outcomes. Pretreatment CT scans of the thorax were used to access the tumor site, size, contour, density, vascular and/or bronchial involvement, relationship with pleura, and lymphadenopathy. Results The distinct clinical features of primary lung LELC include no significant predilection for sex, minimal association with a history of smoking, strong association with EBV in Asians, and a predilection for early or locally advanced stage of the disease. Most patients received complete resection and/or chemotherapy and radiotherapy. The 2- and 5-year overall survival rates for all patients were 81% and 51%, respectively. The common CT findings of primary lung LELC include peripheral nodules that have direct contact with the adjacent pleural surface, with a lesion density that is homogenous and sometimes heterogenous. Conclusions Radiologists should consider the diagnosis of LELC when encountering solitary peripheral pulmonary nodules that have direct contact with the pleural surface in EBV endemic areas, and an EBV-encoded small nuclear RNA test should be performed on histologic specimens of patients meeting these clinical criteria.

Rationale and Objectives: To evaluate the dual-phase helical computed tomography (CT) appearance of small hepato- cellular carcinoma (SHCC) with hypodense and to evaluate its correlation with pathology. Materials and Methods: The helical CT dual-phase appearance of 33 lesions with keeping hypodense was retrospectively analyzed, all lesions were confirmed as SHCC by histopathology. CT appearance included border, inner density. Results: In 33 lesions, which were confirmed as SHCC by pathology, keeping hypodense during hepatic arterial phase and portal venous phase, 19 lesions are ill-defined borders and 14 lesions are well-defined borders, 22 lesions show homogenous hypodense and 11 lesions show heterogeneous hypodense in non-enhancing CT scan; however, only 9 lesions are ill-defined borders and the other 24 lesions are well-defined borders with slightly irregular contours, only 9 lesions show homogenous hypodense and the other 24 lesions show heterogenous hypodense with flecks of more hypodense in enhancing CT scan. Conclusion: SHCC with hypodense prefers to have a well-defined border with slightly irregular contour, and flecks of more hypodense in the lesion in dual-phase enhancing helical CT scan.