High b-Value and Ultra-High b-Value Diffusion Weighted MRI in Stroke.

PURPOSE: To explore the application value of high-b-value and ultra-high b-value DWI in noninvasive evaluation of ischemic infarctions. STUDY TYPE: Prospective. SUBJECTS: Sixty-four patients with clinically diagnosed ischemic lesions based on symptoms and DWI. FIELD STRENGTH/SEQUENCE: 3.0 T/T2-weighted fast spin-echo, fluid-attenuated inversion recovery, pre-contrast T1-weighted magnetization prepared rapid gradient echo sequence, multi-b-value trace DWI and q-space sampling sequences. ASSESSMENT: Lesions were segmented on standard b-value DWI (SB-DWI, 1000 s/mm2), high b-value DWI (HB-DWI, 4000 s/mm2) and ultra-high b-value DWI (UB-DWI, 10,000 s/mm2), and cumulative segmented areas were the final abnormality volumes. Normal white matter (WM) areas were obtained after binarization of segmented brain. In 47 patients, fractional anisotropy (FA) and apparent diffusion coefficients (ADCs) at b values of 1000, 4000, and 10,000 s/mm2 were extracted from symmetrical WM masks and lesion masks of contralateral WM (CWM) and lesion-side WM (LWM). STATISTICAL TESTS: Wilcoxon matched-pairs signed-rank test and Pearson correlation analysis. Two-tailed P-values <0.05 were considered statistically significant. RESULTS: Various signals of HB-/UB-DWI (hypo-, iso- or hyper-intensity) were observed in strokes compared with SB-DWI, and some areas with iso-intensity of SB-DWI manifested with hyper-intensity on HB-/UB-DWI. Abnormality volumes from SB-DWI were significantly smaller than those from HB-DWI and UB-DWI (10.32 ± 16.45 cm3, vs. 12.25 ± 19.71 cm3 and 11.83 ± 19.41 cm3), while no significant difference exist in volume between HB-DWI and UB-DWI (P = 0.32). In CWM, FA significantly correlated with ADC4000 and ADC10,000 (maximum r = -0.51 and -0.64), but did not significantly correlate with ADC1000 (maximum r = -0.20, P = 0.17). ADC1000 or ADC4000 of LWM not significant correlated with FA of CWM (maximum r = -0.28, P = 0.06), while ADC10,000 of LWM significantly correlated with FA of CWM (maximum r = -0.46). DATA CONCLUSION: HB- and UB-DWI have potential to be supplementary tools for the noninvasive evaluation of stroke lesions in clinics. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Driver mutations in ADGRL3 are involved in the evolution of ependymoma.

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

[Clinical genetic analysis of an infant with 1q21.3-qter duplication and Xpter-p11 deletion caused by maternal balanced chromosomal translocation].

OBJECTIVE: To investigate the clinical phenotype and genetic diagnosis of an infant featuring multiple hair and hyperbilirubinemia. METHODS: Conventional G-banding analysis, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) for the patient were conducted, G-banding analyses of peripheral blood for the infant's parents were also performed. RESULTS: We investigated an infant who carries a unbalanced, maternally inherited karyotype 46, X, der (X) t (X;1) (p11.22; q21.3) in which CMA and FISH analyses disclosed a 1q21.3q44 duplication of 93.03 Mb and Xp22.33p11.22 deletion of 54.53 Mb. CONCLUSION: The phenotypes of this infant can probably be attributed to the 1q21.3q44 duplication and Xp22.33p11.22 deletion, which were maternally inherited.

Identify glioma recurrence and treatment effects with triple-tracer PET/CT.

BACKGROUND: Differential diagnosis of tumour recurrence (TuR) from treatment effects (TrE), mostly induced by radiotherapy and chemotherapy, is still difficult by using conventional computed tomography (CT) or magnetic resonance (MR) imaging. We have investigated the diagnostic performance of PET/CT with 3 tracers, 13N-NH3, 18F-FDOPA, and 18F-FDG, to identify TuR and TrE in glioma patients following treatment. METHODS: Forty-three patients with MR-suspected recurrent glioma were included. The maximum and mean standardized uptake values (SUVmax and SUVmean) of the lesion and the lesion-to-normal grey-matter cortex uptake (L/G) ratio were obtained from each tracer PET/CT. TuR or TrE was determined by histopathology or clinical MR follow-up for at least 6 months. RESULTS: In this cohort, 34 patients were confirmed to have TuR, and 9 patients met the diagnostic standard of TrE. The SUVmax and SUVmean of 13N-NH3 and 18F-FDOPA PET/CT at TuR lesions were significantly higher compared with normal brain tissue (13N-NH3 0.696 ± 0.558, 0.625 ± 0.507 vs 0.486 ± 0.413; 18F-FDOPA 0.455 ± 0.518, 0.415 ± 0.477 vs 0.194 ± 0.203; both P < 0.01), but there was no significant difference in 18F-FDG (6.918 ± 3.190, 6.016 ± 2.807 vs 6.356 ± 3.104, P = 0.290 and 0.493). L/G ratios of 13N-NH3 and 18F-FDOPA were significantly higher in TuR than in TrE group (13N-NH3, 1.573 ± 0.099 vs 1.025 ± 0.128, P = 0.008; 18F-FDOPA, 2.729 ± 0.131 vs 1.514 ± 0.141, P < 0.001). The sensitivity, specificity and AUC (area under the curve) by ROC (receiver operating characteristic) analysis were 57.7%, 100% and 0.803, for 13N-NH3; 84.6%, 100% and 0.938, for 18F-FDOPA; and 80.8%, 100%, and 0.952, for the combination, respectively. CONCLUSION: Our results suggest that although multiple tracer PET/CT may improve differential diagnosis efficacy, for glioma TuR from TrE, 18F-FDOPA PET-CT is the most reliable. The combination of 18F-FDOPA and 13N-NH3 does not increase the diagnostic efficiency, while 18F-FDG is not worthy for differential diagnosis of glioma TuR and TrE.

Diagnostic performance of multiparametric MRI in the evaluation of treatment response in glioma patients at 3T.

BACKGROUND: MRI is one of the most important techniques to assess the treatment response of gliomas. However, differentiating tumor recurrence (TuR) from treatment effects (TrE) remains challenging. PURPOSE: To compare the diagnostic performance of MR diffusion-weighted imaging (DWI), arterial spin labeling (ASL), proton MR spectroscopy (MRS), and amide proton transfer (APT) imaging in differentiating between TuR and TrE in posttreatment glioma patients. STUDY TYPE: Prospective. POPULATION: Thirty patients with suspected tumor progression. FIELD STRENGTH/SEQUENCE: DWI, ASL, proton MRS, and APT imaging were performed at 3T MR. ASSESSMENT: MR indices, including ADC, relative cerebral blood flow (rCBF), ratios of Cho/Cr, Cho/NAA, and NAA/Cr and APT-weighted (APTw) effect were obtained from DWI, ASL, proton MRS, and APT imaging, respectively. Indices were measured in the contralateral normal-appearing white matter and lesions defined on the Gd-enhanced T1 w image. TuR or TrE was either determined histologically or clinically from longitudinal MRI follow-up for at least 6 months. STATISTICAL TESTS: The diagnostic performance of the indices was evaluated using Student's t-test, receiver operating characteristic (ROC) curve, and multivariate logistic regression analyses. RESULTS: Among the 30 patients, 16 were diagnosed as having TuR and the rest having TrE. The recurrent tumors showed a significantly higher APTw effect (1.56 ± 1.14%) and rCBF (1.44 ± 0.61) compared with lesions representing treatment effects (-0.44 ± 1.34% and 0.72 ± 0.25, respectively, with P < 0.001). The areas under the curve (AUCs) were 0.87 and 0.90 for APTw and rCBF, respectively, in differentiating between TuR and TrE. Combining APTw and rCBF achieved a higher AUC of 0.93. MRS index ratios of Cho/Cr (P = 0.25), Cho/NAA (P = 0.16), and NAA/Cr (P = 0.86) and ADC (P = 0.37) showed no significant differences between TuR and TrE lesions, with AUCs lower than 0.70. DATA CONCLUSION: Compared with DWI and MRS, ASL and APT imaging techniques showed better diagnostic capability in distinguishing TuR from TrE. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2020;51:1154-1161.

Dual-energy spectral CT quantitative parameters for the differentiation of Glioma recurrence from treatment-related changes: a preliminary study.

BACKGROUND: Differentiating glioma recurrence from treatment-related changes can be challenging on conventional imaging. We evaluated the efficacy of quantitative parameters measured by dual-energy spectral computed tomographic (CT) for this differentiation. METHODS: Twenty-eight patients were examined by dual-energy spectral CT. The effective and normalized atomic number (Zeff and Zeff-N, respectively); spectral Hounsfield unit curve (λHU) slope; and iodine and normalized iodine concentration (IC and ICN, respectively) in the post-treatment enhanced areas were calculated. Pathological results or clinicoradiologic follow-up of ≥2 months were used for final diagnosis. Nonparametric and t-tests were used to compare quantitative parameters between glioma recurrence and treatment-related changes. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and accuracy were calculated using receiver operating characteristic (ROC) curves. Predictive probabilities were used to generate ROC curves to determine the diagnostic value. RESULTS: Examination of pre-contrast λHU, Zeff, Zeff-N, IC, ICN, and venous phase ICN showed no significant differences in quantitative parameters (P > 0.05). Venous phase λHU, Zeff, Zeff-N, and IC in glioma recurrence were higher than in treatment-related changes (P < 0.001). The optimal venous phase threshold was 1.03, 7.75, 1.04, and 2.85 mg/cm3, achieving 66.7, 91.7, 83.3, and 91.7% sensitivity; 100.0, 77.8, 88.9, and 77.8% specificity; 100.0, 73.3, 83.3, and 73.3% PPV; 81.8, 93.3, 88.9, and 93.3% NPV; and 86.7, 83.3, 86.7, and 83.3% accuracy, respectively. The respective areas under the curve (AUCs) were 0.912, 0.912, 0.931, and 0.910 in glioma recurrence and treatment-related changes. CONCLUSIONS: Glioma recurrence could be potentially differentiated from treatment-related changes based on quantitative values measured by dual-energy spectral CT imaging.

AgsA response to cadmium and copper effects at different temperatures in Escherichia coli.

Small heat shock proteins (sHsps), present from prokaryotes to eukaryotes, are a highly conserved molecular chaperone family. They play a crucial role in protecting organisms against cellular insults from single or multiple environmental stressors including heavy metal exposure, heat or cold shock, oxidative stress, desiccation, etc. Here, the toxicity of cadmium and copper, and their ability to modify the cellular growth rate at different temperatures in Escherichia coli cells were tested. Also, the response mechanism of the sHSP aggregation-suppressing protein (AgsA) in such multiple stress conditions was investigated. The results showed that the half effect concentration (EC50 ) of cadmium in AgsA-transformed E. coli cells at 37°C, 42°C, and 50°C were 11.106, 29.50, and 4.35 mg/L, respectively, and that of the control cells lacking AgsA were 5.05, 0.93, and 0.18 mg/L, respectively, while the half effect concentration (EC50 ) of copper in AgsA-transformed E. coli cells at 37°C, 42°C, and 50°C were 27.3, 3.40, and 1.28 mg/L, respectively, and that of the control cells lacking AgsA were 27.7, 5.93, and 0.134 mg/L, respectively. The toxicities of cadmium and copper at different temperatures as observed by their modification of the cellular growth rate and inhibitory effects were in a dose-dependent manner. Additionally, biochemical characterization of AgsA protein in cells subjected to cadmium and copper stresses at different temperatures implicated suppressed aggregation of cellular proteins in AgsA-transformed E. coli cells. Altogether, our data implicate the AgsA protein as a sensitive protein-based biomarker for metal-induced toxicity monitoring.

Heterologous expression of AgsA enhances Escherichia coli tolerance to the combined effect of elevated temperature and Zinc toxicity.

Small heat shock proteins (sHSPs) are ubiquitous stress proteins that are able to protect the cells against cellular insults from temperature, heavy metal etc. However, the molecular chaperone roles of sHSPs in enhancing growth and adaptation under combined temperature and metal stresses in Escherichia coli cells have been poorly understood. Here, we analyze the function of recombinant AgsA, a small heat shock protein from Salmonella enterica serovar Typhimurium under combined temperature and zinc stress in E. coli. Our results show that the heterologous expression of AgsA significantly increases the tolerance of E. coli cells to the combined effect of temperature stress and zinc toxicity by maintaining the stability of soluble proteins. Furthermore, there was remarkable and significant difference in the half effect concentration (EC50) of zinc at all temperatures treatments in both test cells. The EC50s of zinc at 37 °C, 42 °C and 50 °C were 15.24 mg/L, 29.30 mg/L, and 5.98 mg/L respectively in the AgsA-transformed E. coli cells, and 3.03 mg/L, 2.38 mg/L, and 0.373 mg/L, respectively in the control cells lacking AgsA. Together, our data indicate a good concentration-response relationship between all three temperatures treatment and zinc toxicity in E. coli, and establish for the first time the combined effects of temperature and zinc toxicity on E. coli cells. Also, the AgsA protein response to combined thermal and metal stress could serve as a molecular biomarker for the assessment of interactive stress damage to the cells.

Papillary thyroid cancer: dual-energy spectral CT quantitative parameters for preoperative diagnosis of metastasis to the cervical lymph nodes.

PURPOSE: To evaluate the use of dual-energy spectral computed tomographic (CT) quantitative parameters compared with the use of conventional CT imaging features for preoperative diagnosis of metastasis to the cervical lymph nodes in patients with papillary thyroid cancer. MATERIALS AND METHODS: This study was approved by the ethics committee and all patients provided written informed consent. Analyses of quantitative gemstone spectral imaging data and qualitative conventional CT imaging features were independently performed by different groups of radiologists. Excised lymph nodes were located and labeled during surgery according to location on preoperative CT images and were evaluated histopathologically. Single and combined parameters were fitted to simple and multiple logistic regression models, respectively, by means of the generalized estimating equations method. Sensitivity and specificity analyses were performed by using receiver operating characteristic curves and were compared with data from the qualitative analysis. RESULTS: The slope of the spectral Hounsfield unit curve ( λHU slope of the spectral Hounsfield unit curve ), normalized iodine concentration, and normalized effective atomic number measured during both arterial and venous phases were significantly higher in metastatic than in benign lymph nodes. The best single parameter for detection of metastatic lymph nodes was venous phase λHU, with sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 62.0%, 91.1%, 80.6%, 79.7%, and 81.0%, respectively. The best combination of parameters was venous phase λHU slope of the spectral Hounsfield unit curve and arterial phase normalized iodine concentration, with values of 73.0%, 88.4%, 82.9%, 78.0%, and 85.3%, respectively. Compared with qualitative analysis, the venous phase λHU slope of the spectral Hounsfield unit curve showed higher specificity (91.1% vs 83.0%, P < .001) and similar sensitivity (62.0% vs 61.9%, P > .99), and the combined venous phase λHU slope of the spectral Hounsfield unit curve and arterial phase normalized iodine concentration showed higher sensitivity (73.0% vs 61.9%, P < .001) and specificity (88.4% vs 83.0%, P < .001). CONCLUSION: Quantitative assessment with gemstone spectral imaging quantitative parameters showed higher accuracy than qualitative assessment of conventional CT imaging features for preoperative diagnosis of metastatic cervical lymph nodes in patients with papillary thyroid cancer.

Retention of iceberg lettuce quality by low temperature storage and postharvest application of 1-methylcyclopropene or gibberellic acid.

This study was conducted to evaluate the changes in quality of iceberg lettuce during storage at different temperatures and the effects of postharvest treatments of 1-methylcyclopropene or gibberellic acid at high temperature. The results showed that quality of the lettuce was remarkably retained during storage at 0 °C, but significantly declined at 20 °C. However, quality of the vegetable at shelf-temperature (20 °C, 85 ~ 95% RH) was effectively delayed by the treatment with 1-methylcyclopropene (1-MCP) or gibberellic acid (GA). Browning of the lettuce leaves was significantly inhibited by the storage at low temperature and by treatment with1-MCP and GA. The biochemical analysis further indicated that the reduction of soluble protein and sugar, decrease in activity of polyphenol oxidase (PPO) and peroxidase (POD) and accumulation of free amino acids in the lettuce leaves during storage could be remarkably prevented by low temperature, treatment with1-MCP or GA. Our result suggested that 1-MCP or GA treatment would provide a potential way for controlling quality of the lettuce under suboptimal postharvest temperature conditions.

A Study on Prognosis of Diffuse Glioma Based on Clinical Factors and Magnetic Resonance Imaging Radiomics.

OBJECTIVE: To construct an optimal prognostic model to assess the prognosis of patients with diffuse glioma. METHODS: Preoperative magnetic resonance imaging and clinical data were retrospectively collected from 266 patients (training cohort: validation cohort=7:3) with pathologically confirmed diffuse gliomas. A radiomics prognostic model (R-model) based on the radiomics features was constructed. A prognostic model based on clinical factors (C-model) and a fusion model (F-model) was also constructed. Based on the optimal model of three models, the nomogram was constructed. Finally, a "Prognosis Calculator for Diffuse Glioma" was constructed based on the nomogram. RESULTS: The c-index of the R-, C-, and F-models in the validation cohort was 0.742, 0.796, and 0.814, respectively. In the validation cohort, the 1-year area under the curve of the R-, C-, and F-models was 0.749, 0.806, and 0.836, respectively; the 3-year area under the curve was 0.896, 0.966, and 0.963, respectively. In the training cohort, validation cohort, all cohorts, and different grades of glioma cohorts, F-model (optimal model) could identify low- and high-risk groups well. The "Prognosis Calculator for Diffuse Glioma" was available at https://github.com/HDCurry/prognosis. CONCLUSIONS: Among the three models, the F-model (radiomics combined with clinical factors) had optimal predictive efficacy and could more accurately assess the prognosis of diffuse glioma. The "Prognosis Calculator for Diffuse Glioma" constructed based on this model could assist clinicians in more easily and accurately assessing the prognosis of patients with diffuse glioma, thus enabling them to make more reasonable treatment strategies.

Neurosurgical interventions for patients with nasopharyngeal carcinoma: a single institution experience.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a frequent head and neck cancer in southern China and Southeast Asia. The majority of NPC patients are managed by radiation oncologists, medical oncologists and head and neck surgeons. Actually, neurosurgical interventions are warranted under specific circumstances. In this article, we described our experience as neurosurgeons in the management of NPC patients. METHODS: Medical records of NPC patients who received neurosurgical procedure at Sun Yat-sen University Cancer Center were reviewed. RESULTS: Twenty-seven patients were identified. Among 27 cases, neurosurgical procedures were performed in 18 (66.7%) with radiation-induced temporal necrosis, 2 (7.4%) with radiation-induced sarcoma, 4 (14.8%) with synchronous NPC with primary brain tumors, 2 (7.4%) with recurrent NPC involving skull base, and 1 (3.7%) with metachronous skull eosinophilic granuloma, respectively. The diagnosis is challenging in specific cases and initial misdiagnoses were found in 6 (22.2%) patients. CONCLUSIONS: For NPC patients with intracranial or skull lesions, the initial diagnosis can be occasionally difficult because of the presence or a history of NPC and related treatment. Unawareness of these entities can result in misdiagnosis and subsequent improper treatment. Neurosurgical interventions are necessary for the diagnosis and treatment for these patients.

Adjuvant Temozolomide Chemotherapy With or Without Interferon Alfa Among Patients With Newly Diagnosed High-grade Gliomas: A Randomized Clinical Trial.

Importance: High-grade gliomas (HGGs) constitute the most common and aggressive primary brain tumor, with 5-year survival rates of 30.9% for grade 3 gliomas and 6.6% for grade 4 gliomas. The add-on efficacy of interferon alfa is unclear for the treatment of HGG. Objectives: To compare the therapeutic efficacy and toxic effects of the combination of temozolomide and interferon alfa and temozolomide alone in patients with newly diagnosed HGG. Design, Setting, and Participants: This multicenter, randomized, phase 3 clinical trial enrolled 199 patients with newly diagnosed HGG from May 1, 2012, to March 30, 2016, at 15 Chinese medical centers. Follow-up was completed July 31, 2021, and data were analyzed from September 13 to November 24, 2021. Eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed HGG and had received no prior chemotherapy, radiotherapy, or immunotherapy for their HGG. Interventions: All patients received standard radiotherapy concurrent with temozolomide. After a 4-week break, patients in the temozolomide with interferon alfa group received standard temozolomide combined with interferon alfa every 28 days. Patients in the temozolomide group received standard temozolomide. Main Outcomes and Measures: The primary end point was 2-year overall survival (OS). Secondary end points were 2-year progression-free survival (PFS) and treatment tolerability. Results: A total of 199 patients with HGG were enrolled, with a median follow-up time of 66.0 (95% CI, 59.1-72.9) months. Seventy-nine patients (39.7%) were women and 120 (60.3%) were men, with ages ranging from 18 to 75 years and a median age of 46.9 (95% CI, 45.3-48.7) years. The median OS of patients in the temozolomide plus interferon alfa group (26.7 [95% CI, 21.6-31.7] months) was significantly longer than that in the standard group (18.8 [95% CI, 16.9-20.7] months; hazard ratio [HR], 0.64 [95% CI, 0.47-0.88]; P = .005). Temozolomide plus interferon alfa also significantly improved median OS in patients with O6-methylguanine-DNA methyltransferase (MGMT) unmethylation (24.7 [95% CI, 20.5-28.8] months) compared with temozolomide (17.4 [95% CI, 14.1-20.7] months; HR, 0.57 [95% CI, 0.37-0.87]; P = .008). Seizure and influenzalike symptoms were more common in the temozolomide plus interferon alfa group, with 2 of 100 (2.0%) and 5 of 100 (5.0%) patients with grades 1 and 2 toxic effects, respectively (P = .02). Finally, results suggested that methylation level at the IFNAR1/2 promoter was a marker of sensitivity to temozolomide plus interferon alfa. Conclusions and Relevance: Compared with the standard regimen, temozolomide plus interferon alfa treatment could prolong the survival time of patients with HGG, especially the MGMT promoter unmethylation variant, and the toxic effects remained tolerable. Trial Registration: ClinicalTrials.gov Identifier: NCT01765088.

Aurora-A activation, correlated with hypoxia-inducible factor-1α, promotes radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma.

Previously, we and others showed that hypoxia-inducible factor-1α (HIF-1α) and transcriptionally upregulated Aurora-A were required for disease progression in several tumors. Here, we address the clinicopathologic value of Aurora-A and HIF-1α in locally advanced nasopharyngeal carcinoma (NPC). Aurora-A and HIF-1α expression was semiquantitatively evaluated by immunohistochemistry staining in 144 cases from a randomized controlled trial. Of these patients, 69 received neoadjuvant chemotherapy plus concurrent chemoradiotherapy, and acted as the training set, and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy were used as the testing set to validate the prognostic effect of Aurora-A and HIF-1α. We found that Aurora-A and HIF-1α were highly expressed in NPC, but were deficient in normal adjacent epithelia. In the testing set, Aurora-A overexpression predicted a shortened 5-year overall survival (59.1% vs 82.5%, P = 0.024), progression-free survival (44.8% vs 79.8%, P = 0.004), and distant metastasis-free survival (43.0% vs 17.3%, P = 0.016). Multivariate regression analysis confirmed that Aurora-A was indeed an independent prognostic factor for death, recurrence, and distant metastasis both in the testing set and overall patients. Moreover, a positive correlation between Aurora-A and HIF-1α was detected (P = 0.037). Importantly, although HIF-1α did not show any prognostic effect for patient outcome, the subset with Aurora-A and HIF-1α co-overexpression had the poorest overall, progression-free, and distant metastasis-free survival (all P < 0.05). Our results confirmed that Aurora-A was an independent prognostic factor for NPC. Aurora-A combined with HIF-1α refined the risk definition of the patient subset, thus potentially directing locally advanced NPC patients for more selective therapy.

Nasopharyngeal adenoid cystic carcinoma: magnetic resonance imaging features in ten cases.

Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with high local invasiveness. To date, there is no consensus on the imaging characteristics of NACC. To address this, we retrospectively reviewed 10 cases of NACC and summarized the magnetic resonance imaging (MRI) features. MR images of 10 patients with histologically validated NACC were reviewed by two experienced radiologists. The location, shape, margin, signal intensity, lesion texture, contrast enhancement patterns, local invasion, and cervical lymphadenopathy of all tumors were evaluated. Clinical and pathologic records were also reviewed. No patients were positive for antibodies against Epstein-Barr virus (EBV). The imaging patterns of primary tumors were classified into two types as determined by location, shape, and margin. Of all patients, 7 had tumors with a type 1 imaging pattern and 3 had tumors with a type 2 imaging pattern. The 4 tubular NACCs were all homogeneous tumors, whereas 3 (60%) of 5 cribriform NACCs and the sole solid NACC were heterogeneous tumors with separations or central necrosis on MR images. Five patients had perineural infiltration and intracranial involvement, and only 2 had cervical lymphadenopathy. Based on these results, we conclude that NACC is a local, aggressive neoplasm that is often negative for EBV infection and associated with a low incidence of cervical lymphadenopathy. Furthermore, MRI features of NACC vary in locations and histological subtypes.

Longest survival with primary intracranial malignant melanoma: A case report and literature review.

BACKGROUND: Primary intracranial malignant melanoma (PIMM) is rare, and its prognosis is very poor. It is not clear what systematic treatment strategy can achieve long-term survival. This case study attempted to identify the optimal strategy for long-term survival outcomes by reviewing the PIMM patient with the longest survival following comprehensive treatment and by reviewing the related literature. CASE SUMMARY: The patient is a 47-year-old Chinese man who suffered from dizziness and gait disturbance. He underwent surgery for right cerebellum melanoma and was subsequently diagnosed by pathology in June 2000. After the surgery, the patient received three cycles of chemotherapy but relapsed locally within 4 mo. Following the second surgery for total tumor resection, the patient received an injection of Newcastle disease virus-modified tumor vaccine, interferon, and ß-elemene treatment. The patient was tumor-free with a normal life for 21 years before the onset of the recurrence of melanoma without any symptoms in July 2021. A third gross-total resection with adjuvant radiotherapy and temozolomide therapy was performed. Brain magnetic resonance imaging showed no residual tumor or recurrence 3 mo after the 3rd operation, and the patient recovered well without neurological dysfunction until the last follow-up in June 2022, which was 22 years following the initial treatment. CONCLUSION: It is important for patients with PIMM to receive comprehensive treatment to enable the application of the most appropriate treatment strategies. Long-term survival is not impossible in patients with these malignancies.

A feasible CT feature to differentiate focal-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma.

BACKGROUND: To investigate whether the relative computed tomography (CT) value (rCT) of adjacent pancreatic parenchyma can distinguish focal-type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 13 patients with fAIP and 20 patients with PDAC were included in this study. The rCT was calculated as the ratio of the CT value of adjacent pancreatic parenchyma to that of muscle. The diagnostic performance of rCT for discriminating fAIP from PDAC was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: Both fAIP and PDAC presented hyper-fibrosis histologically and delayed enhancement on CT examination. Moreover, the pancreatic parenchyma of fAIP presented serious inflammation. The mean rCT of the parenchyma was significantly lower in fAIP than in PDAC in all phases. The best diagnostic performance of the rCT value was found in the pancreatic phase, with an area under the ROC curve of 0.912, while the areas under the ROC curve of the portal and delayed phases were 0.812 and 0.754, respectively. The optimal cut-off value for distinguishing fAIP from PDAC was 1.62 in the pancreatic phase. CONCLUSIONS: The rCT of the pancreatic parenchyma during the pancreatic phase may be a feasible CT feature for differentiating fAIP from PDAC.

Molecular Decision Tree Algorithms Predict Individual Recurrence Pattern for Locally Advanced Nasopharyngeal Carcinoma.

Background: Recurrence remains one of the key reasons of relapse after the radical radiation for locally advanced nasopharyngeal carcinoma (NPC). Here, the multiple molecular and clinical variables integrated decision tree algorithms were designed to predict individual recurrence patterns (with VS without recurrence) for locally advanced NPC. Methods: A total of 136 locally advanced NPC patients retrieved from a randomized controlled phase III trial, were included. For each patient, the expression levels of 33 clinicopathological biomarkers in tumor specimen, 3 Epstein-Barr virus related serological antibody titer and 5 clinicopathological variables, were detected and collected to construct the decision tree algorithm. The expression level of 33 clinicopathological biomarkers in tumor specimen was evaluated by immunohistochemistry staining. Results: Three algorithm classifiers, augmented by the adaptive boosting algorithm for variable selection and classification, were designed to predict individual recurrence pattern. The classifiers were trained in the training subset and further tested using a 10-fold cross-validation scheme in the validation subset. In total, 13 molecules expression level in tumor specimen, including AKT1, Aurora-A, Bax, Bcl-2, N-Cadherin, CENP-H, HIF-1α, LMP-1, C-Met, MMP-2, MMP-9, Pontin and Stathmin, and N stage were selected to construct three 10-fold cross-validation decision tree classifiers. These classifiers showed high predictive sensitivity (87.2-93.3%), specificity (69.0-100.0%), and overall accuracy (84.5-95.2%) to predict recurrence pattern individually. Multivariate analyses confirmed the decision tree classifier was an independent prognostic factor to predict individual recurrence (algorithm 1: hazard ration (HR) 0.07, 95% confidence interval (CI) 0.03-0.16, P < 0.01; algorithm 2: HR 0.13, 95% CI 0.04-0.44, P < 0.01; algorithm 3: HR 0.13, 95% CI 0.03-0.68, P = 0.02). Conclusion: Multiple molecular and clinicopathological variables integrated decision tree algorithms may individually predict the recurrence pattern for locally advanced NPC. This decision tree algorism provides a potential tool to select patients with high recurrence risk for intensive follow-up, and to diagnose recurrence at an earlier stage for salvage treatment in the NPC endemic region.

Multiregional radiomics profiling from multiparametric MRI: Identifying an imaging predictor of IDH1 mutation status in glioblastoma.

PURPOSE: Isocitrate dehydrogenase 1 (IDH1) has been proven as a prognostic and predictive marker in glioblastoma (GBM) patients. The purpose was to preoperatively predict IDH mutation status in GBM using multiregional radiomics features from multiparametric magnetic resonance imaging (MRI). METHODS: In this retrospective multicenter study, 225 patients were included. A total of 1614 multiregional features were extracted from enhancement area, non-enhancement area, necrosis, edema, tumor core, and whole tumor in multiparametric MRI. Three multiregional radiomics models were built from tumor core, whole tumor, and all regions using an all-relevant feature selection and a random forest classification for predicting IDH1. Four single-region models and a model combining all-region features with clinical factors (age, sex, and Karnofsky performance status) were also built. All models were built from a training cohort (118 patients) and tested on an independent validation cohort (107 patients). RESULTS: Among the four single-region radiomics models, the edema model achieved the best accuracy of 96% and the best F1-score of 0.75 while the non-enhancement model achieved the best area under the receiver operating characteristic curve (AUC) of 0.88 in the validation cohort. The overall performance of the tumor-core model (accuracy 0.96, AUC 0.86 and F1-score 0.75) and the whole-tumor model (accuracy 0.96, AUC 0.88 and F1-score 0.75) was slightly better than the single-regional models. The 8-feature all-region radiomics model achieved an improved overall performance of an accuracy 96%, an AUC 0.90, and an F1-score 0.78. Among all models, the model combining all-region imaging features with age achieved the best performance of an accuracy 97%, an AUC 0.96, and an F1-score 0.84. CONCLUSIONS: The radiomics model built with multiregional features from multiparametric MRI has the potential to preoperatively detect the IDH1 mutation status in GBM patients. The multiregional model built with all-region features performed better than the single-region models, while combining age with all-region features achieved the best performance.

GSTM1 polymorphism is related to risks of nasopharyngeal cancer and laryngeal cancer: a meta-analysis.

BACKGROUND: Accumulating data have reported that GSTM1 polymorphism may be related to nasopharyngeal cancer (NPC) and laryngeal cancer (LC). This meta-analysis was performed to investigate the relationship between GSTM1 polymorphism and risks of NPC and LC. METHODS: Pubmed, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched for potential articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the relationship of GSTM1 polymorphism with the risks of NPC and LC. I2>50% or P<0.05 indicates significant heterogeneity. When heterogeneity existed, the random-effects model was used to pool data, otherwise, the fixed-effects model was adopted. Publication bias was detected by Begg's funnel plot and Egger's regression. Quality of each study was evaluated by Newcastle-Ottawa Scale. RESULTS: Thirty-two eligible articles were included. Pooled outcome suggested the significant relationship of GSTM1 null genotype with increased risk of LC (OR =1.28, 95% CI =1.05-1.54). Compared with hospital-based (HB) population, GSTM1 null genotype was also related to increased risk of LC (OR =1.38, 95% CI =1.06-1.80). Positive relationship of GSTM1 null genotype with enhanced risk of NPC was observed (OR =1.43, 95% CI =1.26-1.63). A similar trend was also observed in the subgroup analysis by source of control (population-based [PB]: OR =1.39, 95% CI =1.18-1.63; HB: OR =1.52, 95% CI =1.22-1.89). CONCLUSION: GSTM1 null genotype is related to increased risk of NPC and LC.