Prognostic value of 3′-Deoxy-3′-18F-Fluorothymidine ([18F] FLT PET) in patients with recurrent malignant gliomas

Introduction3′-deoxy-3′-18F-fluorothymidine ([¹⁸F] FLT) PET has been proven to be of value in diagnosis and assessment of glioma grading, in differentiating tumor recurrence from necrosis, in response assessment and in predicting overall survival (OS) in the primary high grade glioma. In this study, we evaluated the value of [¹⁸F] FLT PET-CT in predicting the OS of patients with recurrent malignant glioma.MethodsFifty-six patients with recurrent malignant glioma were enrolled in this prospective study. The PET-CT and contrast-enhanced MRI scans were performed in all patients. Tumor volume was determined from both PET image (proliferative volume, PV) and MRI image (Vol-MRI). Patients were followed up clinically until death. The likelihood of using PET-derived parameters of SUV_max, tumor-to-normal (T/N) ratio, and PV to predict the OS of patients were assessed in comparison with Vol-MRI and other clinical parameters.ResultThe follow up periods for all patients ranged from 1.5 to 35.6 months with median of 9.8 months. Univariate analysis showed that the following parameters were significantly correlated with OS: grade of primary tumor (p = 0.042), Karnofsky performance score (KPS) (p = 0.041), T/N ratio (p < 0.01), Vol-MRI (p = 0.041), and PV (p < 0.001). However, multivariate Cox regression showed that only the PV (p < 0.001) and T/N ratio (p = 0.001) were independent predictors. The thresholds to predict OS were 16.88 cm³ for PV and 10.94 for T/N ratio. Kaplan–Meier analyses using these thresholds showed a significant discrimination between short and long OS groups (p < 0.001).ConclusionThe PV and T/N ratio of tumor on [¹⁸F] FLT PET-CT are independent predictors of survival in patients with recurrent malignant glioma. The PV on [¹⁸F] FLT PET seems to be more predictive than tumor volume on T1-weighted MRI for OS.     

Resectable pancreatic adenocarcinoma: Role of CT quantitative imaging biomarkers for predicting pathology and patient outcomes

BackgroundsPatients with a pancreatic cancer amenable to surgery still have a poor prognosis and high risk of post-operative recurrence. We aimed to assess the value of quantitative imaging biomarkers using computed-tomography (CT) texture analysis to evaluate the pathologic tumor aggressiveness and predict disease-free survival (DFS) in patients with resectable pancreatic adenocarcinoma.MethodsWe retrospectively performed attenuation measurements and texture analysis on the portal-venous phase of the pre-operative CT scan of 99 patients that underwent resection of a pancreatic ductal adenocarcinoma in two university hospitals. Tumor attenuation parameters included: mean attenuation value of the whole tumor (WHOLE-AV), and of the most hypoattenuating area within the tumor (CENTRAL-AV). Tumor heterogeneity parameters included: standard deviation, entropy, skewness, and kurtosis.ResultsTumor attenuation parameters showed significant association with the tumor differentiation grade (CENTRAL-AV, Odds ratio (OR) 0.968, 95% confidence interval (CI) 0.94–0.998) and lymph node invasion (WHOLE-AV, OR 0.886, CI 0.823–0.955). Variables associated with early-recurrence were: lymph node ratio (R² = 0.15), kurtosis (R² = 0.08), and CENTRAL-AV (R² = 0.04). Lymph node ratio (Hazard ratio (HR) 1.02), and CENTRAL-AV (HR 0.98) were independently associated with shorter DFS. Patients with CENTRAL-AV < 62 Hounsfield units had a shorter 1-year DFS (35% versus 68%, p = 0.004).ConclusionTumors that are more hypoattenuating on the portal-venous phase on CT scan are potentially more aggressive with higher tumor grade, greater lymph node invasion, and shorter DFS.     

A proposal for the stratification of the risk of locoregional failure after surgical resection,perioperative high dose rate brachytherapy,and external beam irradiation: The University of Navarre predictive model

PurposeTo develop a simple clinical model predictive of locoregional failure after complete surgical resection followed by perioperative high-dose-rate brachytherapy (PHDRB) and external beam irradiation (EBRT).Patient and MethodsPatients (n = 166) enrolled in several PHDRB prospective studies conducted at the University of Navarre were analyzed. PHDRB was given to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments for negative or close/positive margins along with 45 Gy of EBRT.ResultsAfter a median followup of 7.4 years (range, 3–12+), 50 patients have failed and 116 remain controlled at last followup. Tumor size, with a cutoff point set at 3 cm (p = 0.041) and margin status (positive and <1 mm vs. negative ≥1 mm, p = 0.0001) were independent predictors of locoregional control. These two parameters were used to develop a four-tiered, hierarchical scoring system that stratified patients into low-risk (negative ≥1 mm margins and size ≤3 cm), intermediate-risk (negative ≥1 mm margins, and size >3 cm), high-risk (positive and <1 mm margins and size ≤3 cm), and very high–risk categories (positive and <1 mm margins and size >3 cm). This classification yields 5-year locoregional control rates of 92.3%, 78.0%, 65.5%, and 48.0% for low-, intermediate-, high-, and very high–risk categories, respectively. The predictive ability of the model is highly significant (p = 0.0001) with an area under the curve of 0.72 (0.64–0.81).ConclusionsThe risk of locoregional failure after combined surgical resection, PHDRB, and EBRT is mainly determined by the number of residual clonogens, which is inversely proportional to the status of the surgical margins and directly related to the size of the resected tumor. These two parameters generate a four-tiered predictive model that seems to be valid for a number of different common tumors and clinical settings.     

Prostate brachytherapy in men with gland volume of 100 cc or greater: Technique,cancer control,and morbidity

PurposeTo determine the outcomes of prostate seed implantation in men with prostate volume (PV) of 100 cc or greater (PV100).MethodsA total of 2051 men with localized prostate cancer were treated with permanent prostate brachytherapy of whom 34 (1.7%) had PV100 (mean, 126.2; range, 100–205 cc). The PV100 patients were older (mean, 69 vs. 66 years; p = 0.031), had higher initial prostate-specific antigen level (20.4 vs. 9.6 ng/mL, p < 0.001), and received a lower dose (182 vs. 194 Gy₂ biologic equivalent dose, p = 0.032). There were no differences in clinical stage, Gleason score, and baseline International Prostate Symptom Score. The mean followup time was 6.7 years (range, 2–18). Biochemical freedom from failure (bFFF) was defined using the Phoenix definition.ResultsThe BFFF at 10 years was no different between PV100 and smaller glands (82.4% vs. 84.5%, p = 0.71). At last followup, mean International Prostate Symptom Score for PV100 increased from 8.5 to 9.1 against 7.4 to 9.2 for smaller glands (p = 0.935). Urinary retention rates were higher for PV100 (6/34, 17.6% vs. 148/2017, 7.3%; odds ratio, 2.71; 95% confidence interval, 1.1–6.6; p = 0.038). Postimplant transurethral resection of the prostate was performed in none of the 34 patients with PV100 against 66 of the 2017 patients (3.3%, p < 0.001). Long-term radiation proctitis for PV100 were 1 of 34 (2.9%) against 82 of 2017 (4.1%, p = 0.741). Rectourethral fistula occurred in 4 patients (0.19%), that is, 1 of 34 (2.9%) in PV100 group and 3 of 2017 (0.1%, p < 0.001).ConclusionThis study demonstrates the feasibility of implanting patients with PV100. Very large PV does not influence bFFF. Although urinary retention rates were higher, the long-term urinary symptoms were no different between the two groups. Requirement for transurethral resection of the prostate was no higher in patients with PV100. Radiation proctitis rates were similar for both.     

High-intensity focused ultrasound combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: Long-term follow-up and clinical analysis

ObjectiveHigh-intensity focused ultrasound (HIFU) combined with transarterial chemoembolization (TACE) has been used to treat unresectable HCC, but its long-term effects and major prognostic factors remain to be determined. The purpose of this study was to assess its long-term effects and find major prognostic factors to help us select eligible patients in the future.Methods73 patients with unresectable HCC received follow-up after HIFU + TACE. The variables of sex, age, AFP level, liver function, tumor location, tumor number, tumor size, TNM staging (5th edition), TNM staging (6th edition), portal vein invasion, ultrasonic pathway of HIFU, TACE session and ablation response were evaluated by univariate analysis. Those variables with significant difference were assessed by multivariate analysis.ResultsThe mean follow-up time was 11.7 ± 11.1 months (range, 1–60 months). The median survival time and overall survival rates of 1, 2, 3-year were 12 months, 49.1%, 18.8%, 8.4%, respectively. 45.2% patients achieved complete ablation. At the end of follow-up, 51 patients (69.9%) died from tumor progression (27 patients), liver function failure (18 patients), hemorrhage of upper digestive tract (3 patients) and infection (3 patients). 1 with liver abscess, 2 with serious skin burns and 2 with rib fracture were observed after HIFU. On univariate analysis, age (P = 0.017), tumor size (P = 0.000), tumor number (P = 0.039), the 5th edition of TNM staging (P = 0.023), portal vein invasion (P = 0.02) and ablation response (P = 0.000) had significant difference. On multivariate analysis, ablation response (P = 0.001) and tumor size (P = 0.013) were major prognostic factors.ConclusionHIFU combined with TACE is a safe method with a low rate of severe complications. As major prognostic factors, ablation response and tumor size may help us predict the survival and select eligible patients clinically.     

Tattoos do not affect exercise-induced localised sweat rate or sodium concentration

ObjectivesSkin tattoos have been shown to reduce localised sweat rate and increase sweat sodium concentration ([Na⁺]) when sweating is artificially stimulated. This study investigated whether similar responses are observed with exercise-induced sweating.DesignUnblinded, within-participant control, single trial.MethodsTwenty-two healthy individuals (25.1 ± 4.8 y (Mean ± SD), 14 males) with a unilateral tattoo ≥11.4 cm² in size, ≥2 months in age, and shaded ≥50% participated in this investigation. Participants undertook 20 min of intermittent cycling (4 × 5 min intervals) on a stationary ergometer in a controlled environment (24.6 ± 1.1 °C; 64 ± 6% RH). Resultant sweat was collected into absorbent patches applied at two pairs of contralateral skin sites (pair 1: Tattoo vs. Non-Tattoo; pair 2: Control 1 vs. Control 2 (both non-tattooed)), for determination of sweat rate and sweat [Na⁺]. Paired samples t-tests were used to determine differences between contralateral sites.ResultsTattoo vs. Non-Tattoo: Neither sweat rate (Mean ± SD: 0.92 ± 0.37 vs. 0.94 ± 0.43 mg·cm⁻²·min⁻¹, respectively; p = 0.693) nor sweat [Na⁺] (Median(IQR): 37(32–52) vs. 37(31–45) mM·L⁻¹, respectively; p = 0.827) differed. Control 1 vs. Control 2: Neither sweat rate (Mean±SD: 1.19 ± 0.53 vs. 1.19 ± 0.53 mg·cm⁻²·min⁻¹, respectively; p = 0.917) nor sweat [Na⁺] (Median(IQR): 29(26–41) vs. 31(25–43) mM·L⁻¹, respectively; p = 0.147) differed. The non-significant differences for sweat rate and [Na⁺] between Tattoo vs. Non-Tattoo were inside the range of the within participant variability (sweat rate CVi = 5.4%; sweat [Na⁺] CVi = 4.4%).ConclusionsSkin tattoos do not appear to alter the rate or [Na⁺] of exercise-induced sweating. The influence of skin tattoos on localised sweat responses may have previously been over-estimated.     

Comparison of perioperative automated versus manual two-dimensional tumor analysis in glioblastoma patients

ObjectivesCurrent recommendations for the measurement of tumor size in glioblastoma continue to employ manually measured 2D product diameters of enhancing tumor. To overcome the rater dependent variability, this study aimed to evaluate the potential of automated 2D tumor analysis (ATA) compared to highly experienced rater teams in the workup of pre- and postoperative image interpretation in a routine clinical setting.Materials and methodsFrom 92 patients with newly diagnosed GB and performed surgery, manual rating of the sum product diameter (SPD) of enhancing tumor on magnetic resonance imaging (MRI) contrast enhanced T1w was compared to automated machine learning-based tumor analysis using FLAIR, T1w, T2w and contrast enhanced T1w.ResultsPreoperative correlation of SPD between two rater teams (1 and 2) was r = 0.921 (p < 0.0001). Difference among the rater teams and ATA (p = 0.567) was not statistically significant. Correlation between team 1 vs. automated tumor analysis and team 2 vs. automated tumor analysis was r = 0.922 and r = 0.897, respectively (p < 0.0001 for both). For postoperative evaluation interrater agreement between team 1 and 2 was moderate (Kappa 0.53). Manual consensus classified 46 patients as completely resected enhancing tumor. Automated tumor analysis agreed in 13/46 (28%) due to overestimation caused by hemorrhage and choroid plexus enhancement.ConclusionsAutomated 2D measurements can be promisingly translated into clinical trials in the preoperative evaluation. Immediate postoperative SPD evaluation for extent of resection is mainly influenced by postoperative blood depositions and poses challenges for human raters and ATA alike.     

Vitamin d is related to gait recovery after total hip arthroplasty: A prospective analysis

ObjectivesTo investigate the association between baseline serum levels of 25-hydroxyvitamin D (25(OH)D) and gait pattern in patients undergoing total hip arthroplasty (THA).MethodsProspective study of patients with hip osteoarthritis undergoing primary THA between January 2012 and December 2013. Blood samples were collected on the day of hospital admission. Gait analyses were performed before surgery and 3 months postoperatively. Internal moments were captured.ResultsMajor improvements were observed in gait data after THA. 25(OH)D levels correlated with change in peak extension (R = 0.25, p = 0.017) and peak power generation (R = 0.25, p = 0.04). Multiple linear regression analyses were performed. In model 1, 25(OH)D and change in gait speed explained the variability of peak extension (R2 = 0.1, p = 0.004). In model 2, only 25(OH)D explained the variability of peak power generation (R2 = 0.05, p = 0.044).Conclusions25(OH)D levels were correlated with change in peak extension and peak power generation. The effect of 25(OH)D on change in gait variables after THA is modest.     

Antilipolytic drug boosts glucose metabolism in prostate cancer

IntroductionThe antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts.MethodsSubcutaneous tumors were produced in nude mice by injection of PC3 and CWR22Rv1 PCa cells. The mice were divided into two groups (Acipimox vs. controls). Acipimox (50 mg/kg) was administered by oral gavage 1 h before injection of tracers. 1 h after i.v. co-injection of 8.2 MBq (222 ± 6.0 μCi) ¹⁸ F-FDG and ~ 0.0037 MBq (0.1 μCi) ¹⁴C-acetate, ¹⁸ F-FDG imaging was performed using a small-animal PET scanner. Counting rates in reconstructed images were converted to activity concentrations. Quantification was obtained by region-of-interest analysis using dedicated software. The mice were euthanized, and blood samples and organs were harvested. ¹⁸ F radioactivity was measured in a calibrated γ-counter using a dynamic counting window and decay correction. ¹⁴C radioactivity was determined by liquid scintillation counting using external standard quench corrections. Counts were converted into activity, and percentage of the injected dose per gram (%ID/g) tissue was calculated.ResultsFDG biodistribution data in mice with PC3 xenografts demonstrated doubled average %ID/g tumor tissue after administration of Acipimox compared to controls (7.21 ± 1.93 vs. 3.59 ± 1.35, P = 0.02). Tumor-to-organ ratios were generally higher in mice treated with Acipimox. This was supported by PET imaging data, both semi-quantitatively (mean tumor FDG uptake) and visually (tumor-to-background ratios). In mice with CWR22Rv1 xenografts there was no effect of Acipimox on FDG uptake, either in biodistribution or PET imaging. ¹⁴C-acetate uptake was unaffected in PC3 and CWR22Rv1 xenografts.ConclusionsIn mice with PC3 PCa xenografts, acute administration of Acipimox increases tumor uptake of ¹⁸ F-FDG with general improvements in tumor-to-background ratios. Data indicate that administration of Acipimox prior to ¹⁸ F-FDG PET scans has potential to improve sensitivity and specificity in patients with castration-resistant advanced PCa.     

The contribution of situational probability information to anticipatory skill

ObjectivesTo determine the contribution of situational probability information to the anticipatory responses of skilled tennis players representative of two different stages of development.DesignParticipants were required to predict the location of tennis serves presented to them on a plasma touchscreen from the perspective of the receiver.MethodsServes were sequenced into a series of games and sets with a score presented before each point, typical of a game of tennis. The game score was manipulated to provide advance probability information. The location of the serve for the first point of each game was always directed to the same location. A total of 12 service games consisting of 96 points were presented with interest in whether players would detect the relationship between the game score and resultant serve location.ResultsA 2 × 12 (age × service game) ANOVA with repeated measures on the second factor revealed a significant age by service game interaction for response time (F_11, 297 = 3.86, p < 0.05, η_p² = .12). The older players picked up the occurrence of the first point service pattern after the ninth service game whereas the younger, players did not. There were no significant response accuracy differences between the groups in relation to the first point.ConclusionsThe findings highlight the important role of situational probability information, in addition to movement kinematics, for successful anticipatory performance and suggest that the pick-up of such information is not utilised by younger players.     

Heart rate and blood lactate responses during Taekwondo training and competition

ObjectiveThe study investigated physical fitness characteristics of elite Taekwondo (TKD) players as well as their heart rate (HR) response and blood lactate concentration changes during TKD specific exercises and simulated competition.MethodsAnaerobic and aerobic power has been evaluated in eight elite TKD players (age: 20 ± 1 years, body mass: 70.8 ± 6 kg, Ht: 179.9 ± 4 cm). We also measured heart rate and blood lactate concentration during competition and specific-exercises (front kicks during 10 s, 1 and 3 min).ResultsMaximum oxygen uptake (VO₂max) and peak anaerobic power (Wpeak) averaged 56.22 ± 2.57 ml min^–1 kg^–1 and 12.1 ± 1.7 W kg^–1, respectively. HR and blood lactate [La] concentrations increased significantly during competition (F = 19.4, P < 0.001; F = 21.3, P < 0.001) compared to the resting value. HR and [La] values were significantly correlated with those measured during 10 s (R = 0.85, P < 0.05 and R = 0.79, P < 0.05, respectively) and 3-min specific exercises (R = 0.95, P < 0.01 and R = 0.76, P < 0.05).ConclusionsTKD requires high levels of both aerobic and anaerobic physical fitness. The correlation between specific exercises and competition is of practical interest for TKD players and trainers.     

Contribution of autonomic dysfunction to abnormal exercise blood pressure in type 2 diabetes mellitus

ObjectivesThe purpose of this study was to compare the presence and severity of autonomic dysfunction in type 2 diabetes mellitus patients, with and without exaggerated blood pressure responses to exercise.DesignWe performed a cross-sectional analysis of 98 patients with type 2 diabetes mellitus (aged 59 ± 9).MethodsBoth time (standard deviation of RR intervals, root-mean-square of successive RR interval differences) and frequency (total spectral power, high frequency, low frequency, very low frequency) domains of heart rate variability were analysed in a 5 min recording at rest and 20 min after a maximal treadmill test. An exaggerated blood pressure response to exercise was identified by peak blood pressure ≥190/105 mm Hg (women) or ≥210/105 mm Hg (men).ResultsEach group of either exaggerated exercise blood pressure response or normal blood pressure response consisted of 49 patients. At rest there were no significant differences between groups for all time and frequency domain parameters of heart rate variability. Post-exercise, there was a significant (p < 0.05) reduction in the SDNN, RMSSD and TP in the exaggerated exercise blood pressure group. Independent correlates (p < 0.01) of exercise systolic blood pressure included post-exercise TP, resting systolic blood pressure, cardiac autonomic neuropathy and beta-blockers (beta = ?0.28, adj. R² = 0.32, p < 0.001).ConclusionsReduced post-exercise heart rate variability in patients with type 2 diabetes mellitus, with an exaggerated exercise blood pressure response suggests preclinical autonomic dysfunction characterized by impaired vagal modulation.     

Balance dysfunction in hereditary and spontaneous spastic paraparesis

ObjectiveTo determine how postural sway is affected in people with spastic paraparesis (pwSP) and the impact of different impairments.MethodsIn 20 pwSP and 18 matched healthy controls standing postural sway was measured with eyes open and closed. Vibration threshold, isometric ankle and hip muscle strength and ankle stiffness with the participant at rest or preactivating the muscle was measured.ResultsAntero-posterior (AP) and medio-lateral (ML) sway was higher in pwSP. Muscle strength was reduced and ankle stiffness increased in pwSP. Increased vibratory threshold was seen in 35% of participants. Higher total ankle stiffness (R² = 0.44) was associated with lower AP sway with eyes open whilst hip abductor weakness was associated with increased ML sway with eyes open (R² = 0.36) or closed (R² = 0.47) or AP sway with the eyes closed (R² = 0.48).ConclusionsThe degree of postural sway was related to muscle paresis of the hip abductors particularly in the ML direction and under conditions of reduced sensory input. People with higher total ankle stiffness have less AP sway suggesting that this may help to stabilise the body.     

Comparison between acoustic radiation force impulse quantification data and perfusion-CT parameters in hepatocellular carcinoma

ObjectiveTo find out, if ultrasound elastography of hepatocellular carcinoma (HCC) can predict patterns of tumor perfusion in volume perfusion computed tomography (VPCT).Material and methods25 consecutive patients (mean age, 68.9; range, 51–85 years) with liver cirrhosis suspected of HCC underwent VPCT and acoustic radiation force impulse (ARFI) elastography the same day. Quantitative elasticity values were registered, while blood flow (BF), blood volume (BV) and hepatic perfusion index (HPI) of the HCC lesions were calculated. Additionally, we identified histologic WHO grading, lesion size and localization. The Siemens Acuson S 3000 HELX-System with Virtual Touch™-Software and Siemens Somatom Definition Flash with Syngo^® software were used.ResultsA total of 43 HCC lesions were assessed. Mean shear wave velocity was 2.6 m/s (range, 1.1–4.3 m/s). There was no significant linear correlation between the elasticity values and BF (p = 0.751), BV (p = 0.426) and HPI (p = 0.437). However, elasticity values were higher, the larger the tumor was (p = 0.008). Shear wave velocity declined with increasing distance of the HCC to the skin surface (p = 0.028) and depending on liver segment. In addition, elasticity values were higher in less differentiated HCCs. This trend was not statistically significant (p = 0.842).ConclusionTissue elasticity in HCC does not correlate with the degree of tumor vascularization, but calculated values are influenced both by the tumor size and localization inside the liver.     

A new screening method to detect proximal dental caries using fluorescence imaging

ObjectivesThis study aimed to assess the screening performance of the quantitative light-induced fluorescence (QLF) technology to detect proximal caries using both fluorescence loss and red fluorescence in a clinical situation. Moreover, a new simplified QLF score for the proximal caries (QS-Proximal) is proposed and its validity for detecting proximal caries was evaluated as well.MethodsThis clinical study included 280 proximal surfaces, which were assessed by visual-tactile and radiographic examinations and scored by each scoring system according to lesion severity. The occlusal QLF images were analysed in two different ways: (1) a quantitative analysis producing fluorescence loss (ΔF) and red fluorescence (ΔR) parameters; and (2) a new QLF scoring index. For both quantitative parameters and QS-Proximal, the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) were calculated as a function of the radiographic scoring index at the enamel and dentine caries levels.ResultsBoth ΔF and ΔR showed excellent AUROC values at the dentine caries level (ΔF = 0.860, ΔR = 0.902) whereas a relatively lower value was observed at the enamel caries level (ΔF = 0.655, ΔR = 0.686). The QS-Proximal also showed excellent AUROC ranged from 0.826 to 0.864 for detecting proximal caries at the dentine level.ConclusionThe QS-Proximal, which represents fluorescence changes, showed excellent performance in detecting proximal caries using the radiographic score as the gold standard.     

Expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer

BackgroundThe mechanism underlying the increased levels of protoporphyrin IX in bladder cancer remains unclear. Here, we focus on proteins associated with protoporphyrin IX accumulation in bladder cancer cells and investigate the protein that plays a key role in increased protoporphyrin IX accumulation in bladder cancer cells.MethodsWestern blotting was used to determine the expression of peptide transporter 1, hydroxymethylbilane synthase, ferrochelatase, ATP-binding cassette 2, and heme oxygenase-1 in bladder cancer cell line cells. We evaluated the correlation between the expression of each protein and accumulated protoporphyrin IX in these cells using Pearson's correlation analysis. Immunohistochemistry was used to estimate the expression of the same five proteins in samples from 75 patients who underwent transurethral resection of bladder tumors. The correlation between the expression of each protein in cells from resected bladder specimens and accumulated protoporphyrin IX in bladder cancer cells in voided urine was evaluated using Pearson's correlation analysis.ResultsThe expression of ferrochelatase showed a significant negative correlation with protoporphyrin IX accumulation in vitro (p = 0.04). The expression of peptide transporter 1 (p < 0.01, R = 0.39), heme oxygenase-1 (p < 0.01, R = 0.33), and ferrochelatase (p < 0.01, R = 0.75) in resected bladder specimens by immunohistochemistry was correlated with protoporphyrin IX accumulation in bladder cancer cells in voided urine. On multivariate analysis, the expression of ferrochelatase (p = 0.03) was significant factors to predict positive 5-aminolevulinic acid-induced fluorescent cytology.ConclusionThe expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer.     

Diagnostic performance of contrast-enhanced CT-scan in sinusoidal obstruction syndrome induced by chemotherapy of colorectal liver metastases: Radio-pathological correlation

PurposeSinusoidal obstruction syndrome (SOS) is a likely side effect of colorectal liver metastases (CRLM) chemotherapy. This study aimed to assess computed tomography scan (CT-scan) performance for SOS diagnosis for patients receiving neoadjuvant chemotherapy (NC) prior to CRLM surgery, comparing obtained results with pathological gold standard.MethodsPreoperative CT-scans of 67 patients who had received a NC prior to liver resection for CRLM from 2011 to 2016 were retrospectively analysed. Positive diagnosis and severity of SOS were established after consensual review of the slides by three pathologists. Preoperative CT-scans were separately interpreted by two radiologists and evocative signs of SOS were sought, defined according to a literature review and operators experience. In order to identify SOS predictors, univariate analysis and multivariate logistic regression were used to study CT-scan signs and pathological results correlation.ResultsTwenty-nine patient (43%) had an SOS, 22 (33%) were low-grade and 7 (10%) were high-grade. All patient had received a median of 6 cures (3–27) containing Oxaliplatin for 53 (79%) of them. In univariate analysis, hepatic heterogeneity (p < 0.001), puddle-like or micronodular appearance (p < 0.001), peripheral distribution of heterogeneity (p = 0.085), clover-like sign (p = 0.02), splenomegaly (p = 0.0026), spleen volume increase ≥30% (p = 0.04) or splenic length increase ≥15% (p = 0.04), as well as the subjective impression of the observer (P < 0.001) were significantly associated with SOS diagnosis. In multivariate analysis, clover-like sign (OR 1.87, 95% CI 1.18–2.95, p = 0.0081), increase in spleen volume ≥30% (OR 1.29, 95% CI 1.01–1.64, p = 0.04), and the peripheral distribution of heterogeneity (OR 1.53, 95% CI 1.21–1.94, p < 0.001) were independent SOS predictors. The area under the ROC curve was 0.804. The inter-observer agreement for SOS diagnosis was moderate (Kappa = 0.546).ConclusionCT-scan can detect suggestive signs of SOS in patients receiving chemotherapy for CRLM. By integrating clinical and biological information into CT-scan data, it may be fruitful to create a positive diagnostic and severity score for chemotherapy-induced SOS.     

Contrast-enhanced multiphasic CT and MRI findings of adenosquamous carcinoma of the pancreas

ObjectiveThe objective was to retrospectively study computed tomography (CT) and magnetic resonance imaging (MRI) findings of adenosquamous carcinoma of the pancreas (PASC).Materials and MethodsTwelve patients (six women and six men; mean age, 61.3 years; range, 47–78 years) who presented with PASC as documented by pathologic examination underwent CT (n= 10) or both CT and MRI (n= 2) examination. Two radiologists evaluated the images and determined the location, size, margin, internal attenuation or signal intensity, contrast enhancement, and pattern for each tumor. Additionally, the presence of poorly enhanced areas, upstream main pancreatic duct (MPD) dilatation, pancreatic atrophy, and peripancreatic tissue metastasis were evaluated. Images were cross-referenced to surgical and pathologic findings.ResultsMasses were distributed throughout the pancreas (head, n= 6; body, n= 1; and tail, n= 5). The tumor size ranged from 2.4 to 5.5 cm with an average size of 3.7 cm. Eight (66.7%) masses were ill defined, and seven (58.3%) were partially exophytic. Twelve (100%) masses showed heterogeneous and poorly enhanced areas. The lesions showed weak (n= 5), moderate (n= 5), or intense (n= 2) progressive enhancement. The diameter of MPD in six patients ranged from 3.0 to 5.0 mm with an average of 3.7 mm. Pancreatic atrophy was not found. In 10 patients (83.3%), masses invaded the peripancreatic tissues. Two patients had metastatic liver disease at presentation.ConclusionPASC typically presented as an ill-defined, hypovascular mass with a poorly enhanced area, exophytic tendency, and peripancreatic tissue invasion. Lack of pancreatic atrophy and mild MPD dilatation were also distinct from common duct pancreatic adenocarcinoma.     

A new method to reduce false positive results in breast MRI by evaluation of multiple spectral regions in proton MR-spectroscopy

ObjectivesTo investigate whether the evaluation of multiple spectral regions can increase the diagnostic performance of ¹H-MRS of the breast and reduce false positive findings.Methods93 patients (mean age 56 years, range 23–79) undergoing breast MRI for routine clinical indications on a 1.5 T scanner were eligible for this IRB-approved prospective study. Suspicious enhancing lesions ≥8 mm underwent single-voxel point-resolved ¹H-MRS (PRESS, TR = 2000 ms, TE = 272 ms). Histology showed 69 malignant and 24 benign lesions. The Signal-to-Noise ratio of choline, olefinic acids and the water-to-methylene ratio were measured. The area under the ROC-curve (AUC) was used to evaluate single measurements. Combined diagnostic accuracy was explored using a 10-fold cross-validated Chi-squared automatic interaction detection (CHAID) analysis. Inter-reader agreement was evaluated in a subset of patients.ResultsA significant AUC for differentiation between benign and malignant lesions was identified for choline (0.733, P = 0.001), olefinic acids (0.769, P = 0.0001) and water-to-methylene ratio (0.704, P = 0.003). All three variables were included in a classification algorithm using CHAID methodology. Using this classification, 70.8% (17/24) false positive diagnoses in benign lesions would have been avoided. Inter-reader agreement was almost perfect.ConclusionsThe combined evaluation of multiple spectral regions can increase the diagnostic performance of ¹H-MRS and potentially reduce false positive findings.