Insights into the pattern of choroidal vascularity index changes in idiopathic macular hole.

This retrospective study aimed to investigate the changes in choroidal vascularity index (CVI) before and after surgery for idiopathic macular hole (MH). Enhanced depth imaging optical coherence tomography (EDI-OCT) images were analyzed at baseline and at 1-week, 1-month, and 3-month postoperative visits. A total of 97 patients (97 eyes) were included in the study. At baseline, overall CVI and macular CVI showed negative correlation with axial length (AL) and positive correlation with central corneal thickness (CCT). There were no significant differences in macular CVI or overall CVI between affected and healthy eyes, as well as in subgroup analysis of different stages of macular CVI. Following surgery, there was a significant decrease in CVI at 1 week postoperatively, followed by a gradual recovery to baseline levels over time. The observed changes in CVI may be attributed to factors such as air tamponade, pressure changes, and photoreceptor metabolism. This study provides insights into the pattern of CVI changes associated with MH surgery. The findings suggest that stage 4 MH is associated with decreased macular CVI in affected eyes. These results contribute to a better understanding of the effects of surgery on choroidal blood flow in MH patients.

Impact of preoperative [18F]FDG PET/CT vs. contrast-enhanced CT in the staging and survival of patients with clinical stage I and II non-small cell lung cancer: a 10-year follow-up study.

OBJECTIVES: To elucidate the impact of [18F]FDG positron emission tomography/computed tomography (PET/CT) vs. CT workup on staging and prognostic evaluation of clinical stage (c) I-II NSCLC. METHODS: We retrospectively identified 659 cI-II NSCLC who underwent CT (267 patients) or preoperative CT followed by PET/CT (392 patients), followed by curative-intended complete resection in our hospital from January 2008 to December 2013. Differences were assessed between preoperative and postoperative stage. Five-year disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier approach and compared with log-rank test. Impact of preoperative PET/CT on survival was assessed by Cox regression analysis. RESULTS: The study included 659 patients [mean age, 59.5 years ± 10.8 (standard deviation); 379 men]. The PET/CT group was superior over CT group in DFS [12.6 vs. 6.9 years, HR 0.67 (95% CI 0.53-0.84), p < 0.001] and OS [13.9 vs. 10.5 years, HR 0.64 (95% CI 0.50-0.81), p < 0.001]. In CT group, more patients thought to have cN0 migrated to pN1/2 disease as compared with PET/CT group [26.4% (66/250) vs. 19.2% (67/349), p < 0.001], resulting in more stage cI cases being upstaged to pII-IV [24.7% (49/198) vs. 16.1% (47/292), p = 0.02], yet this was not found in cII NSCLC [27.5% (19/69) vs. 27.0% (27/100), p = 0.94]. Cox regression analysis identified preoperative PET/CT as an independent prognostic factor of OS and DFS (p = 0.002, HR = 0.69, 95% CI 0.54-0.88; p = 0.004, HR = 0.72, 95% CI 0.58-0.90). CONCLUSION: Addition of preoperative [18F]FDG PET/CT was associated with superior DFS and OS in resectable cI-II NSCLC, which may result from accurate staging and stage-appropriate therapy.

Immune cell identity behind the Ktrans mapping of mouse glioblastoma.

Dynamic contrast-enhanced MR imaging (DCE-MRI) can assess the integrity of the blood brain barrier (BBB) and has been used in GBM patients to determine glioma grade, predict prognosis, evaluate treatment response, and differentiate treatment-induced effect from recurrence. The volume transfer constant Ktrans is the most frequently used metric in tumor assessment. Based on previous studies that a higher WHO grade of brain tumor was associated with greater impairments of immunity and that Ktrans value was associated with the pathological grading, the relationship between differential composition of immune cells in GBM tissue and dynamic changes in Ktrans mapping was anticipated in this study. The present study utilized an orthotopic allograft model of GBM in which mouse GL26 cells are implanted into Ccr2RFP/wtCx3cr1GFP/wt mice on a C57 background. The brain tumors exhibited heterogenous Ktrans values with the coefficients of variation (CV) above 75%, or relatively homogeneous Ktrans maps with CV values below 50%. The Ktrans values of homogeneous tumors ranged between 0.02/min-0.32/min with a median value of 0.10/min. The immune cell composition defined by quantitative immunohistochemistry and cell sorting was compared between the tumors with Ktrans values above 0.10/min (higher Ktrans) or below 0.10/min (lower Ktrans). Histological analysis showed that tumors with higher Ktrans values exhibited greater numbers of CCR2pos cells (257.60 ± 16.42/mm2 vs 203.23 ± 12.20/mm2, p = 0.04) and an increased ratio of CCR2pos cells to CX3CR1pos cells (1.20 ± 0.02 vs 0.38 ± 0.04, p = 0.001), the numbers of CX3CR1pos cells did not differ significantly based on Ktrans values (219.70 ± 16.20/mm2 vs 250.38 ± 21.20/mm2, p = 0.19). Flowcytometry analysis showed that tumors with higher Ktrans values (above 0.1/min) were associated with greater numbers of both overall monocytes (54.93 ± 6.81% vs 29.75 ± 3.54%, p = 0.01) and inflammatory monocytes (72.38 ± 1.49% vs 59.52 ± 2.44%, p = 0.001). In contrast, tumors with lower Ktrans values (below 0.1/min) exhibited greater numbers of patrolling monocytes (75.65 ± 4.14% vs 63 ± 6.94%, p = 0.05). In the tumors with lower Ktrans values, all three types of tumor associated cells, including patrolling monocytes, inflammatory monocytes, and microglia cells possessed a higher proportion of cells at pro-inflammatory status (41.77 ± 6.13% vs 25.06 ± 6.72%, p = 0.05; 27.50 ± 2.11% vs 20.62 ± 1.87%, p = 0.03; and 55.80 ± 9.88% vs 31.12 ± 7.31%, p = 0.05), inflammatory monocytes showed fewer anti-inflammatory cells (1.25 ± 0.62% vs 3.16 ± 3.56%, p = 0.04). Taken together, differences in Ktrans values were associated with differential immune cell phenotypes and polarizations. Ktrans mapping may therefore represent a novel approach for defining the immune status of GBM.

Molecular Identity Changes of Tumor-Associated Macrophages and Microglia After Magnetic Resonance Imaging-Guided Focused Ultrasound-Induced Blood-Brain Barrier Opening in a Mouse Glioblastoma Model.

An orthotopically allografted mouse GL26 glioma model (Ccr2RFP/wt-Cx3cr1GFP/wt) was used to evaluate the effect of transient, focal opening of the blood-brain barrier (BBB) on the composition of tumor-associated macrophages and microglia (TAMs). BBB opening was induced by magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS) combined with microbubbles. CX3CR1-GFP cells and CCR2-RFP cells in brain tumors were quantified in microscopic images. Tumors in animals treated with a single session of MRgFUS did not exhibit significant changes in cell numbers when compared with tumors in animals not receiving FUS. However, tumors that received two or three sessions of MRgFUS had significantly increased amounts of both CX3CR1-GFP and CCR2-RFP cells. The effect of MRgFUS on immune cell composition was also characterized and quantified using flow cytometry. Glioma implantation resulted in increased amounts of lymphocytes, monocytes and neutrophils in the brain parenchyma. Tumors administered MRgFUS exhibited increased numbers of monocytes and monocyte-derived TAMs. In addition, MRgFUS-treated tumors exhibited more CD80+ cells in monocytes and microglia. In summary, transient, focal opening of the BBB using MRgFUS combined with microbubbles can activate the homing and differentiation of monocytes and induce a shift toward a more pro-inflammatory status of the immune environment in glioblastoma.

Insights into the underlying choroid in different stages of idiopathic epiretinal membranes after Viteromacular surgery.

PURPOSE: The purpose of the study was to longitudinally investigate the correlation between choroidal morphologic and vascular parameters and postoperative visual outcome in different stages of idiopathic epiretinal membranes (iERMs). METHODS: A prospective, observational, institutional case series of 102 consecutive patients diagnosed with unilateral iERMs were recruited at Peking University Third Hospital and were followed up for 12 months after surgical treatment with vitrectomy. Participants were classified into four stages according to current staging scheme. All eligible subjects underwent standardized imaging evaluation of choroidal parameters including subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), and choroidal capillary perfusion (CCP) at baseline and each follow-up by enhanced depth optical coherence tomography (EDI-OCT) and OCT angiography (OCTA). Longitudinal follow-up of choroidal parameters over 12 months was analysed, and their correlations with best-corrected visual acuity (BCVA) were also assessed for predictive prognostic value. RESULTS: CVI and CCP were significantly correlated with BCVA at each follow-up examination (all p < 0.05). However, SFCT exhibited no variation among different stages of iERMs at baseline (p = 0.981) or during follow-up (p = 0.520). The preoperative CVI correlated with 12-month postoperative BCVA (p < 0.001) and its predictive prognostic effect on BCVA was validated in multiple regression analysis (p = 0.006). CONCLUSION: CVI varied among different stages of iERM and was significantly correlated with visual outcomes after the surgery. CVI could serve as a predictive prognostic marker in iERMs, which further indicates the underlying choroid should be taken into consideration in clinical evaluation of iERMs.

Dynamic 18 F-FDG PET/CT can predict the major pathological response to neoadjuvant immunotherapy in non-small cell lung cancer.

Major pathological response (MPR) is a potential surrogate for overall survival. We determined whether the dynamic changes in 18 F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) were associated with MPR in patients receiving neoadjuvant immunotherapy. Forty-four patients with stage II-III non-small cell lung cancer (NSCLC) who received neoadjuvant immunotherapy and radical surgery were enrolled. Moreover, 18 F-FDG PET/CT scans were performed at baseline and within 1 week before surgery to evaluate the disease. All histological sections were reviewed to assess MPR. The detailed clinical features of the patients were analyzed. The reliability of the clinical variables was assessed in differentiating between MPR and non-MPR using logistic regression. Receiver-operating characteristic (ROC) curve analysis identified the SUVmax changes threshold most associated with MPR. Most of the patients were pathologically diagnosed with squamous cell carcinoma and received anti-PD-1 antibodies plus chemotherapy. The immunotherapy regimens included nivolumab, pembrolizumab, and camrelizumab. MPR was observed in more than half of lesions. Tumors with MPR had a higher decrease in the longest dimension on dynamic PET/CT than those without MPR. Furthermore, the decline in SUVmax was significantly different between MPR and non-MPR diseases, and MPR lesions had a prominent mean reduction in SUVmax. SUVmax reduction was independently associated with MPR in the multivariate regression. On ROC analysis, the threshold of SUVmax decrease in 60% was associated with MPR. Dynamic changes in SUVmax were associated with MPR. The tumors with MPR showed a greater PET/CT response than those without MPR. A SUVmax decrease of more than 60% is more likely to result in an MPR after receiving neoadjuvant immunotherapy.

Physiologically intense FDG uptake of distal spinal cord on total-body PET/CT.

OBJECTIVE: Physiologically mild-to-moderate FDG uptake of the spinal cord was reported. However, we noticed intense FDG uptake of distal spinal cord in several patients without definite spinal cord lesions on total-body PET/CT. Thus, this study aimed to investigate the frequency, pattern, intensity, and associations of FDG uptake in such cases on total-body PET/CT. METHODS: The clinical characteristics of age, gender, body mass index (BMI), lower extremity symptom, diabetes, and fasting blood glucose level, and total-body FDG PET/CT metabolic parameters of maximum standard uptake value (SUVmax), SUVmax of lean body mass (SUVlbm), and SUVmax of body surface area (SUVbsa), were retrospectively analyzed in 527 patients without definite spinal cord lesions. Intense FDG uptake was defined as greater than liver glucometabolism on visual analysis, and T5 cord was selected as cord background. RESULTS: Intense FDG uptake of distal spinal cord was observed in 87 out of 527 patients (16.5%) and involved with 2-3 vertebral segments including T11-T12 in 33 cases (38.0%), T12-L1 in 29 (33.3%), and T11-L1 in 25 (28.7%). No lesions were demonstrated on follow-up physical examinations, MRI or contrast-enhanced CT in these 87 cases with intense FDG accumulation in the distal spinal cord. The median SUVmax, SUVlbm, and SUVbsa of distal spinal cord with intense FDG uptake were 3.8 (2.7-5.5), 2.9 (2.2-4.3), and 1.0 (0.7-1.6), respectively. Significant differences in SUVmax, SUVlbm, and SUVbsa of distal cord and cord background were found between the groups with and without intense FDG uptake (P < 0.05). Moreover, significant differences in ratios of distal spinal cord-to-cord background, to mediastinal blood pool, and to liver were observed between two groups (P < 0.05). Intense FDG uptake of distal cord was associated with age, diabetic status, and blood glucose level. CONCLUSIONS: Intense FDG uptake of distal spinal cord on total-body PET/CT may be physiological, more common in younger age, patients without diabetes, or lower fasting blood glucose.

CVIS: Automated OCT-scan-based software application for the measurements of choroidal vascularity index and choroidal thickness.

PURPOSE: To develop an automated image recognition software for the objective quantification of choroidal vascularity index (CVI) and choroidal thickness (CT) at different choroidal locations on images obtained from enhanced depth imaging optical coherence tomography (EDI-OCT), and to validate its reliability and investigate the difference and correlation between measurements made by manual and software. METHODS: A total of 390 EDI-OCT scans, captured from 130 eligible emmetropic or myopic subjects, were categorized into four grades in terms of their accessibility to identify the choroidal-scleral interface (CSI) and were further assessed for CT and CVI at five locations (subfoveal, nasal, temporal, superior and inferior) by the newly developed Choroidal Vascularity Index Software (CVIS) and three ophthalmologists. Choroidal parameters acquired from CVIS were evaluated for its reliability and correlation with ocular factors, in comparison to manual measurements. Distribution of difference and correlation coefficient between CVIS and manual measurements were also analysed. RESULTS: Choroidal Vascularity Index Software (CVIS) demonstrated excellent intra-session reliability for CT (ICC: 0.992) and CVI (ICC: 0.978) measurements, compared to the relatively lower intra- and inter-observer reliability of manual measurements. Choroidal Vascularity Index Software (CVIS) and manual assessments had the highest correlation at nasal choroid (CT: r = 0.829, p < 0.001; CVI: r = 0.665, p < 0.001). Choroidal parameters identified with CVIS showed stronger correlations with axial length than manual measurements. CONCLUSION: This automated software, CVIS, exhibited excellent reliability compared to manual measurements, which are subject to image quality and clinical experience. With its validated clinical relevance, CVIS holds promise to serve as a flexible and robust tool in future vitreoretinal and chorioretinal studies.

Visual functional defects in patients with type 2 diabetes mellitus: a questionnaire based cross-sectional study.

PURPOSE: To determine the impact of type 2 diabetes mellitus (T2DM) on visual functions, identify different modifiers as risk or protective factors, and find out how these factors affect patients' visual symptoms and visual functions as a whole. METHODS: We performed an online survey among 1030 participants (400 patients, 630 non-patients). Demographic features and severity of disease were documented, while visual functions were evaluated using National Eye Institute Visual Functioning questionnaire-25 (NEI VFQ-25). Independent t-test, analysis of variance, linear and nonlinear regression models were used to assess all data. RESULTS: Scores other than color vision among T2DM patients were significantly lower compared with non-T2DM participants. There was significant difference after stratification of age and education, but no significant difference between different genders was observed. Parameters including duration of T2DM, fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c) negatively impacted on the scores, with 20 years' of diabetic duration, 10 mmol/L of FPG, 7.5% of HbA1c being potential cut-off points. Poorer best corrected visual acuity (BCVA) and diagnosis of diabetic retinopathy were risk factors, while they simultaneously produced mediation effect, contributing 5%-78% of effect in the deterioration of visual functions caused by longer diabetic duration and higher blood glucose. CONCLUSION: Significant visual impairments and faster deterioration in visual functions were seen in T2DM patients, with older age, lower educational level, longer diabetic duration, poorer blood glucose administration, limited BCVA, and the presence of diabetic retinopathy identified as risk factors. Average BCVA and diabetic retinopathy also yielded mediation effect as diabetic duration lengthened and blood glucose elevated.

Ellipsoid Zone and External Limiting Membrane-Related Parameters on Spectral Domain-Optical Coherence Tomography and Their Relationships With Visual Prognosis After Successful Macular Hole Surgery.

Purpose: To compare structural diameters of the ellipsoid zone (EZ) and external limiting membrane (ELM) bands on spectral domain-optical coherence tomography (SD-OCT) images between vision-improved (group A) and vision-unimproved (group B) patients, and investigate the connection between these parameters and visual prognosis. Materials and Methods: Forty-five eyes of 43 patients with idiopathic full-thickness macular hole closed after vitrectomy were retrospectively reviewed. Best-corrected visual acuity (BCVA) and SD-OCT were conducted preoperatively and at 1 week, 1 month and 6 months postoperatively. Structural and functional parameters were then measured using ImageJ software. Results: Among structural and functional parameters, the relative reflectivity of EZ and the ratio of continuous ELM and EZ in group A were significantly higher than in group B from the 1-month postoperative visit. At the 6-month follow-up, the diameter of EZ disruption in group A was significantly smaller than in group B, and the relative reflectivity of ELM/EZ was significantly higher than group B. At 6-months, BCVA was statistically significantly correlated with baseline BCVA, basal diameter (BD), macular hole index (MHI), and diameter of ELM/EZ disruption. Change in BCVA from baseline was found to be significantly correlated with axial length and diameter hole index (DHI). Conclusions: Postoperative BCVA outcome was significantly correlated with integrity, thickness and reflectivity of the EZ band. Patients with smaller diameter of EZ disruption and higher reflectivity of EZ band tended to have better visual outcomes. Given that the EZ band reflects the recovery of mitochondria in photoreceptors, it is a promising parameter for their functional evaluation.

Non-invasive, neurotoxic surgery reduces seizures in a rat model of temporal lobe epilepsy.

Surgery can be highly effective for treating certain cases of drug resistant epilepsy. The current study tested a novel, non-invasive, surgical strategy for treating seizures in a rat model of temporal lobe epilepsy. The surgical approach uses magnetic resonance-guided, low-intensity focused ultrasound (MRgFUS) in combination with intravenous microbubbles to open the blood-brain barrier (BBB) in a transient and focal manner. During the period of BBB opening, a systemically administered neurotoxin (Quinolinic Acid: QA) that is normally impermeable to the BBB gains access to a targeted area in the brain, destroying neurons where the BBB has been opened. This strategy is termed Precise Intracerebral Non-invasive Guided Surgery (PING). Spontaneous recurrent seizures induced by pilocarpine were monitored behaviorally prior to and after PING or under control conditions. Seizure frequency in untreated animals or animals treated with MRgFUS without QA exhibited expected seizure rate fluctuations frequencies between the monitoring periods. In contrast, animals treated with PING targeting the intermediate-temporal aspect of the hippocampus exhibited substantial reductions in seizure frequency, with convulsive seizures being eliminated entirely in two animals. These findings suggest that PING could provide a useful alternative to invasive surgical interventions for treating drug resistant epilepsy, and perhaps for treating other neurological disorders in which aberrant neural circuitries play a role.

Choroidal Morphologic and Vascular Features in Patients With Myopic Choroidal Neovascularization and Different Levels of Myopia Based on Image Binarization of Optical Coherence Tomography.

Purpose: To characterize the choroidal morphologic and vascular features in different levels of myopes and patients with myopic choroidal neovascularization (mCNV). Methods: A total of 148 subjects were enrolled in this cross-sectional study, including 78 low-to-moderate myopes (LMM), 53 high myopes (HM), and 17 high myopic patients with mCNV. Ocular biometrics were measured using an optical low-coherence reflectometry device. Retinal and choroidal imaging was performed using enhanced depth imaging (EDI) spectral domain optical coherence tomography (OCT). Retinal parameters including retinal thickness and retinal volume were obtained from a built-in software. Binarization technique was adopted to investigate choroidal parameters including choroidal thickness (CT), vascular area, stromal area, and choroidal vascularity index (CVI). Choroidal parameters were measured at five locations to cover as much area of choroid as possible, and their patterns of distribution were further analyzed. Results: Patients with mCNV had an atrophic retina of comparable thickness to HM (273.65 ± 17.28 vs. 276.49 ± 13.29 µm, p = 0.47), but the choroid was thinner than that of HM (153.94 ± 15.12 vs. 236.09 ± 38.51 µm, p < 0.001). Subfoveal CVI was greatest in the mCNV eyes (0.651 ± 0.009), followed by HM (0.645 ± 0.012) and LMM eyes (0.636 ± 0.012). Similar to CT, CVI was also found significantly different among these three groups at all five locations (p for trend < 0.001 for all locations). Axial length (AL) was negatively correlated with retinal volume (r = -0.236, p = 0.009), which is the only significant finding in associations between ocular factors and retinal parameters. Strong, negative correlations were identified between AL and subfoveal choroidal thickness (SFCT, r = -0.820, p < 0.001). However, AL was positively correlated with subfoveal CVI (r = 0.668, p < 0.001). CVI was greater in myopic eyes with thinner choroid (r = -0.578, p < 0.001). BCVA exhibited no significant association with CVI (r = 0.139, p = 0.092), but was negatively correlated with SFCT (r = -0.386, p < 0.001) and positively correlated with AL (r = 0.351, p < 0.001). Conclusion: Choroid in patients with mCNV was thinner yet more vascularized than that in HM and LMM subjects. CVI increased with a longer AL which was associated with a smaller SFCT, choroidal vascular area (VA), and total choroidal area (TCA). Better BCVA was achieved in subjects with thicker SFCT and shorter AL.

A New Prognostic Index Combines the Metabolic Response and RECIST 1.1 to Evaluate the Therapeutic Response in Patients With Non-Small Cell Lung Cancer.

Aim: Response Evaluation Criteria in Solid Tumors (RECIST) is occasionally insufficient for evaluation. We proposed a new prognostic index (NPI) that combines the standardized uptake value (SUV), metabolic tumor volume (MTV), and RECIST. Methods: In total, 116 patients with lung cancer who underwent consecutive positron emission tomography-computed tomography prior to and after the initial treatment were included. We formulated the NPI by estimating the hazard ratios of overall survival for ΔMTV, ΔSUVmax, and ΔD (tumor size based on RECIST). Progression-free survival (PFS) and overall survival (OS) were compared between RECIST and the NPI. Results: ROC curve analysis identified two cutoff values based on the NPI (≤ -49.3% and ≥43.4%) to discriminate partial remission (NPR), stable disease (NSD) and progressive disease (NPD). Based on RECIST, survival analysis did not discriminate significantly on either PFS or OS between the PR, SD, and PD groups. However, according to the NPI, PFS and OS differed significantly between the NPR, NSD, and NPD groups (training set: PFS, p = 0.048; OS, p = 0.026; validation set: PFS, p = 0.004; OS, p = 0.023). Moreover, therapeutic response based on NPI was independent prognostic factor for both PFS [NPR as reference, NSD: hazard ratio (HR) 2.04; 95% confidence interval (95% CI) 1.35-3.08; p = 0.001; NPD: HR 6.87; 95% CI 3.03-15.57; p < 0.001] and OS (NPR as reference, NSD: HR 1.64; 95% CI 1.05-2.57; p = 0.031; NPD: HR 3.56; 95% CI 1.59-7.95; p = 0.002). Conclusion: The NPI showed superiority for evaluation of the therapeutic response and survival for patients with non-small cell lung cancer, overcoming the limitations of RECIST.

Expert Consensus on clinical application of FDG PET/CT in infection and inflammation.

To further promote the clinical application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in infection and inflammation and standardize the diagnostic process, the experts in relevant fields in China carried out discussion and formed the Expert Consensus on the clinical application of FDG PET/CT in infection and inflammation. This consensus is intended to provide a reference for imaging physicians to select a reasonable diagnostic plan. However, it should be noted that it couldn't include or solve all the problems in clinical operation. Imaging physicians and technicians should develop a comprehensive and reasonable diagnostic procedure according to their professional knowledge, clinical experience and currently available medical resources when facing specific patients.

Predictive value of 18F-FDG PET/CT in patients with acute type B aortic intramural hematoma.

BACKGROUND: The clinical course and predictors of adverse aortic events (AAE) in patients with acute Stanford type B intramural hematoma (IMH) remain controversial. This study aimed to investigate whether 18F-FDG PET/CT can predict risk in patients with acute type B IMH. METHODS AND RESULTS: This study included 34 patients with acute type B IMH who underwent PET/CT within 14 days from the onset of symptoms. The maximal standardized uptake values (SUVmax) of 18F-FDG uptake was significantly different between patients with or without AAE (4.3 ± 0.6 vs 3.7 ± 1.0, P = 0.020), but not the target to blood ratio (TBR, SUVmax divided by SUV in the superior vena cava) (1.6 ± 0.2 vs 1.5 ± 0.5, P = 0.064). In patients with initial ulcer-like projection (ULP), a blood-filled pouch protruding into the IMH, which was seen in 25 patients(74%), both the SUVmax and TBR were significantly higher in patients who developed AAE, (4.3 ± 0.6 vs 3.3 ± 0.5, P = 0.001; 1.6 ± 0.2 vs 1.4 ± 0.2, P = 0.01); the TBR >1.5, which is determined from receiver-operating-characteristic curve, had a sensitivity of 73% and a specificity of 80% in predicting AAE. CONCLUSION: Patients with ULP and high 18F-FDG uptake were more likely to develop AAE and may require closer surveillance with serial imaging.

18F-FDGPET/CT in fever of unknown origin and inflammation of unknown origin: a Chinese multi-center study.

PURPOSE: To evaluate the clinical value of 18F-FDG-PET/CT for the diagnosis of fever of unknown origin (FUO) and inflammation of unknown origin (IUO) in Chinese population, as well as the characteristics of PET/CT in different category of etiological disease. METHODS: A total of 376 consecutive patients with FUO/IUO who underwent FDG-PET/CT at 12 hospitals were retrospectively studied. FDG uptake was quantitatively and visually evaluated, by using SUVmax and a 4-grade scale respectively. A questionnaire survey to the clinicians was used to evaluate the significance of PET/CT in diagnosing of FUO/IUO. Data analysis included the etiological distribution in the study population, image characteristics in different category of diseases, and clinical significance of PET/CT. RESULTS: In 376 studied patients, the infectious diseases accounted for 33.0% of patients, rheumatologic diseases for 32.4%, malignancies for 19.1%, miscellaneous causes for 6.6%, and cause unknown for 8.8%. However, the etiological distribution among hospitals was varied. In addition, the etiological disease composition ratio has changed over time in China. On PET/CT examinations, 358 (95.2%) of the patients had a positive finding. Within them, local high uptake lesion was found in 219 cases, and nonspecific abnormal uptake (NAU) was found in 187 cases. FDG uptake in malignant diseases was significantly higher than in other category diseases both on SUVmax and visual scores (t-value range from 4.098 to 5.612, all P value < 0.001). Based on a clinical questionnaire survey, PET/CT provided additional diagnostic information for 77.4% of patients, and 89.6% of patients benefited from PET/CT examination. CONCLUSIONS: FDG PET/CT is a valuable tool for clinical diagnosis of FUO/IUO, and it is of great significance in further investigating the usefulness of PET/CT in non-neoplastic diseases.

Mixed Responses to Systemic Therapy Revealed Potential Genetic Heterogeneity and Poor Survival in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: A subset of patients with non-small cell lung cancer (NSCLC) fosters mixed responses (MRs) to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) or chemotherapy. However, little is known about the clinical and molecular features or the prognostic significance and potential mechanisms. METHODS: The records of 246 consecutive patients with NSCLC receiving single-line chemotherapy or TKI treatment and who were assessed by baseline and interim positron emission tomography/computed tomography scans were collected retrospectively. The clinicopathological correlations of the MR were analyzed, and a multivariate analysis was performed to explore the prognostic significance of MR. RESULTS: The overall incidence of MR to systemic therapy was 21.5% (53/246) and predominated in patients with stage IIIB-IV, EGFR mutations and those who received TKI therapy (p < .05). Subgroup analyses based on MR classification (efficacious versus inefficacious) showed significant differences in subsequent treatment between the two groups (p < .001) and preferable progression-free survival (PFS) and overall survival (OS) in the efficacious MR group. Multivariate analyses demonstrated that the presence of MR was an independent unfavorable prognostic factor for PFS (hazard ratio [HR], 1.474; 95% confidence interval [CI], 1.018-2.134; p = .040) and OS (HR, 1.849; 95% CI, 1.190-2.871; p = .006) in patients with NSCLC. Induced by former systemic therapy, there were more T790M (18%), concomitant EGFR mutations (15%), and changes to EGFR wild type (19%) in the MR group among patients with EGFR mutations, which indicated higher incidence of genetic heterogeneity. CONCLUSION: MR was not a rare event in patients with NSCLC and tended to occur in those with advanced lung adenocarcinoma treated with a TKI. MR may result from genetic heterogeneity and is an unfavorable prognostic factor for survival. Further studies are imperative to explore subsequent treatment strategies. The Oncologist 2017;22:61-69Implications for Practice: Tumor heterogeneity tends to produce mixed responses (MR) to systemic therapy, including TKI and chemotherapy; however, the clinical significance and potential mechanisms are not fully understood, and the subsequent treatment after MR is also a clinical concern. The present study systemically assessed patients by PET/CT and differentiated MR and therapies. The study identified a relatively high incidence of MR in patients with advanced NSCLC, particularly those treated with targeted therapies. An MR may be an unfavorable prognostic factor and originate from genetic heterogeneity. Further studies are imperative to explore subsequent treatment strategies.

PIK3CA is critical for the proliferation, invasiveness, and drug resistance of human tongue carcinoma cells.

PIK3CA is an oncogene component of phosphatidylinositol 3-kinase (PI3K) signaling pathway and is associated with cell proliferation and carcinogenesis in a variety of human cancers. PIK3CA mutation is correlated with the aggressiveness of many epithelial cancers. And so PIK3CA is considered as a major oncogene in many human epithelial malignancies. However, its role in tongue carcinoma is unknown. We used lentiviral-mediated interfering short hairpin RNAs (shRNAs) to knock down PIK3CA expression in tongue carcinoma Tca8113 cells, and then we tested the cell proliferation by MTT assay and cell invasiveness by cell invasion assay. To examine whether PIK3CA is involved in the response of Tca8113 cells to an anticancer drug, cisplatin, we further performed cell death analysis by fluorescence-activated cell sorting (FACS). We found that knocking down PIK3CA led to slower cell growth and lessened cell invasiveness. In addition, PIK3CA downregulation increased Tca8113 cell death after cisplatin treatment, suggesting that PIK3CA downregulation might be helpful to increase the effects of some anticancer drugs. Moreover, in a mouse model of established large sized OSCC, we showed that suppression of PIK3CA markedly diminished tumorigenicity in vivo. To understand its molecular mechanism of action, we measured expression of phospho-PTEN (Ser380) and phospho-AKT (Ser473) by Western blot and found that suppression of PIK3CA inhibited OSCC growth through downregulation of p-PTEN and p-AKT. Our study highlights critical roles for PIK3CA in the tongue cancer, and suggests that PIK3CA gene might be considered as a therapeutic target for clinical tongue cancer.

[Clinical value of PET in identifying cervical nodal metastases of tongue cancer: a comparison with CT/MRI and clinical palpation in 38 cases].

OBJECTIVE: To assess the value of PET in the identification of cervical nodal metastases of tongue cancer in comparison with CT/MRI and clinical palpation. METHODS: Thirty-eight patients with tongue cancer underwent PET and CT/MRI within 2 weeks before surgery. The results of PET, CT/MRI, and clinical palpation were interpreted separately to assess the regional lymph node status, using histopathological analysis as the golden standard. The differences in the sensitivity, specificity and accuracy among the imaging modalities and clinical palpation were analyzed. RESULTS: The sensitivity of PET for nodal metastasis identification was 11.1% higher than that of CT/MRI (83.3% vs 72.2%, P=0.423) and 16.6% higher than that of clinical palpation (83.3% vs 66.7%, P=0.248). The specificity of PET was 5% higher than that of CT/MRI (80% vs 75%, P=0.703) and 15% higher than that of clinical palpation (80% vs 65%, P=0.288). The accuracy of PET, CT/MRI, and clinical palpation in identifying cervical nodal metastases was 81.6%, 73.7% and 65.8%, respectively. CONCLUSION: The sensitivity, specificity and accuracy of PET for detecting cervical nodal metastases are greater than those of CT/MRI and clinical palpation. Although the results failed to show statistically significant differences, we still recommend that PET be used as a supplementary modality for identifying nodal metastases of tongue cancer.