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Bilateral carpal tunnel syndrome (CTS) is a common extracardiac manifestation of amyloidosis and usually predates overt cardiac amyloidosis (CA) by several years. Screening studies on patients undergoing CTS surgery have shown a low yield of CA (2.0%), but high prevalence of amyloid in the carpal ligament. The proportion of patients with amyloid in the carpal ligament who later develop CA is unknown.The authors sought to investigate the prevalence of undiagnosed CA 5 to 15 years after surgery for bilateral CTS.Using national registries, the authors identified subjects aged 60 to 85 years with prior CTS surgery, where the first procedure on the second wrist was performed 5 to 15 years earlier. Invitations to participate in the study were sent by mail. Per international recommendations, the initial cardiac evaluation included echocardiography,A total of 250 subjects (35.7% of those invited) participated in the study. The median age was 70.4 years, and 50% were female. CA was diagnosed in 12 patients (4.8%; 95% CI: 2.5%-8.2%), and all cases were wild-type transthyretin amyloidosis (ATTRwt). The prevalence of ATTRwt in men was 8.8% (95% CI: 4.5%-15.2%; n = 11), and 21.2% (95% CI: 11.1%-34.7%) in male subjects ≥70 years with a BMI 30 kg/mScreening for CA in patients with prior surgery for bilateral CTS finds approximately 5% with early-stage transthyretin CA. The clinical yield was higher (1 in 5) when focusing on nonobese men ≥70 years, showing potential for systematic screening.

Purpose Cancer has a multitude of phenotypic expressions and identifying these are important for correct diagnosis and treatment selection. Clinical molecular imaging such as positron emission tomography can access several of these hallmarks of cancer non-invasively. Recently, hyperpolarized magnetic resonance spectroscopy with [1-13C] pyruvate has shown great potential to probe metabolic pathways. Here, we investigate simultaneous dual modality clinical molecular imaging of angiogenesis and deregulated energy metabolism in canine cancer patients. Methods Canine cancer patients (n = 11) underwent simultaneous [68Ga]Ga-NODAGA-E[(cRGDyK)]2 (RGD) PET and hyperpolarized [1-13C]pyruvate-MRSI (hyperPET). Standardized uptake values and [1-13C]lactate to total 13C ratio were quantified and compared generally and voxel-wise. Results Ten out of 11 patients showed clear tumor uptake of [68Ga]Ga-NODAGA-RGD at both 20 and 60 min after injection, with an average SUVmean of 1.36 ± 0.23 g/mL and 1.13 ± 0.21 g/mL, respectively. A similar pattern was seen for SUVmax values, which were 2.74 ± 0.41 g/mL and 2.37 ± 0.45 g/mL. The [1-13C]lactate generation followed patterns previously reported. We found no obvious pattern or consistent correlation between the two modalities. Voxel-wise tumor values of RGD uptake and lactate generation analysis revealed a tendency for each canine cancer patient to cluster in separated groups. Conclusion We demonstrated combined imaging of [68Ga]Ga-NODAGA-RGD-PET for angiogenesis and hyperpolarized [1-13C]pyruvate-MRSI for probing energy metabolism. The results suggest that [68Ga]Ga-NODAGA-RGD-PET and [1-13C]pyruvate-MRSI may provide complementary information, indicating that hyperPET imaging of angiogenesis and energy metabolism is able to aid in cancer phenotyping, leading to improved therapy planning.

Background and purpose In radiotherapy, treatment response is generally evaluated many weeks after end of the treatment course. If the treatment outcome could be predicted during radiotherapy better tumour control could be achieved through timely adaptation of the treatment strategy. In this study intra-treatment change based on the diffusion MRI outlined viable tumour volume (VTV) was assessed and compared to the standard GTV to study their outcome prediction capacity. Materials and methods Thirty-eight brain metastases from twenty-one cancer patients were analysed in this prospective trial. Diffusion and structural MRI was acquired on a 1 T machine before, during, and at follow-up 2–3 months after radiotherapy. The VTV was defined as a region with high cellularity using high b-value diffusion MRI scans. Further, the diffusivity of the VTV was derived as the apparent diffusion coefficient (ADC). Treatment outcome was determined using RECIST defined bounds in the T1W MRI follow-up scan. Longitudinal statistical analysis was performed using a linear mixed effect model. Results The GTV declined in both responding and non-responding (significantly) tumours with inseparable rates during radiotherapy. The VTV volume fraction reduced significantly in the responding tumours only. The ADC of the VTV increased significantly in responding metastases whereas it decreased in non-responding metastases. Furthermore, no association between baseline tumour size or primary disease and outcome was observed. Conclusion GTV size change during radiotherapy is not a reliable predictor of outcome in brain metastases. On the other hand, change in the volume fraction of VTV and diffusivity of VTV shows ability to stratify treatment outcome.

Intratumor heterogeneity may contribute to the ambiguous clinical results on PD-L1 status as a predictor for immunotherapy response in patients with HNSCC. This decreases the utility of PD-L1 expression from single tumour biopsies as a predictive biomarker. In this prospective study, intratumor heterogeneity of PD-L1 expression in HNSCC was investigated with both Tumour Proportion Score (TPS) and Combined Positive Score (CPS). Thirty-three whole surgical specimens from 28 patients with HNSCC were included. PD-L1 expression in six random core biopsies from each surgical specimen was used to assess the concordance between multiple biopsies and the negative predictive value of a single negative core biopsy. With 1% cut off, 36% of the specimens were concordant with TPS and 52% with CPS. With a 50% cut-off value the concordance was 70% with TPS and 55% with CPS. Defining a tumour as positive if just a single-one of the biopsies was positive, the negative predictive value (NPV) of a single negative core biopsy was 38.9 and 0% (1% cut off), and 79.9% and 62.8% (50% cut off) for TPS and CPS, respectively. In conclusion, PD-L1 positivity varies markedly within the tumour, both with TPS and CPS, challenging the utility of this biomarker.

Summary: The Scandinavian winter-swimming culture combines brief dips in cold water with hot sauna sessions, with conceivable effects on body temperature. We study thermogenic brown adipose tissue (BAT) in experienced winter-swimming men performing this activity 2–3 times per week. Our data suggest a lower thermal comfort state in the winter swimmers compared with controls, with a lower core temperature and absence of BAT activity. In response to cold, we observe greater increases in cold-induced thermogenesis and supraclavicular skin temperature in the winter swimmers, whereas BAT glucose uptake and muscle activity increase similarly to those of the controls. All subjects demonstrate nocturnal reduction in supraclavicular skin temperature, whereas a distinct peak occurs at 4:30–5:30 a.m. in the winter swimmers. Our data leverage understanding of BAT in adult human thermoregulation, suggest both heat and cold acclimation in winter swimmers, and propose winter swimming as a potential strategy for increasing energy expenditure.

Background: Patient head motion is a major concern in clinical brain MRI, as it reduces the diagnostic image quality and may increase examination time and cost. Purpose: To investigate the prevalence of MR images with significant motion artifacts on a given clinical scanner and to estimate the potential financial cost savings of applying motion correction to clinical brain MRI examinations. Study Type: Retrospective. Subjects: In all, 173 patients undergoing a PET/MRI dementia protocol and 55 pediatric patients undergoing a PET/MRI brain tumor protocol. The total scan time of the two protocols were 17 and 40 minutes, respectively. Field Strength/Sequences: 3 T, Siemens mMR Biograph, MPRAGE, DWI, T 1 and T 2-weighted FLAIR, T 2-weighted 2D-FLASH, T 2-weighted TSE. Assessment: A retrospective review of image sequences from a given clinical MRI scanner was conducted to investigate the prevalence of motion-corrupted images. The review was performed by three radiologists with different levels of experience using a three-step semiquantitative scale to classify the quality of the images. A total of 1013 sequences distributed on 228 MRI examinations were reviewed. The potential cost savings of motion correction were estimated by a cost estimation for our country with assumptions. Statistical Test: The cost estimation was conducted with a 20% lower and upper bound on the model assumptions to include the uncertainty of the assumptions. Results: 7.9% of the sequences had motion artifacts that decreased the interpretability, while 2.0% of the sequences had motion artifacts causing the images to be nondiagnostic. The estimated annual cost to the clinic/hospital due to patient head motion per scanner was $45,066 without pediatric examinations and $364,242 with pediatric examinations. Data Conclusion: The prevalence of a motion-corrupted image was found in 2.0% of the reviewed sequences. Based on the model, repayment periods are presented as a function of the price for applying motion correction and its performance. Evidence Level: 4. Technical Efficacy: Stage 6 J. Magn. Reson. Imaging 2020;52:731–738.

The aim of this study was to evaluate the correlation between uptake of the PET ligand (68)Ga-NOTA-AE105, targeting the urokinase-type plasminogen activator receptor (uPAR), and Gleason score in patients undergoing prostate biopsy. Methods: Patients with clinical suspicion of prostate cancer (PCa) or previously diagnosed with PCa were prospectively enrolled in this phase 2 trial. A combination of uPAR PET and multiparametric MRI (mpMRI) was performed, and the SUV in the primary tumor, as delineated by mpMRI, was measured by 2 independent readers. The correlation between the SUV and the Gleason score obtained by biopsy was assessed. Results: A total of 27 patients had histologically verified PCa visible on mpMRI and constituted the study population. There was a positive correlation between the SUV(max) and the Gleason score (Spearman ρ = 0.55; P = 0.003). Receiver operating characteristic analysis showed an area under the curve of 0.88 (95% CI, 0.67–1.00) for discriminating a Gleason score of greater than or equal to 3 + 4 from a Gleason score of less than or equal to 3 + 3. A cutoff for the tumor SUV(max) could be established with a sensitivity of 96% (79%–99%) and a specificity of 75% (30%–95%) for detecting a Gleason score of greater than or equal to 3 + 4. For discriminating a Gleason score of greater than or equal to 4 + 3 from a Gleason score of less than or equal to 3 + 4, a cutoff could be established for detecting a Gleason score of greater than or equal to 4 + 3 with a sensitivity of 93% (69%–99%) and a specificity of 62% (36%–82%). Conclusion: SUV measurements from uPAR PET in primary tumors, as delineated by mpMRI, showed a significant correlation with the Gleason score, and the tumor SUV(max) was able to discriminate between low-risk Gleason score profiles and intermediate risk Gleason score profiles with a high diagnostic accuracy. Consequently, uPAR PET/MRI could be a promising method for the noninvasive evaluation of PCa and might reduce the need for repeated biopsies (e.g., in active surveillance).

Tattooed patients undergoing magnetic resonance imaging (MRI) can develop cutaneous complications during the procedure. Our aim was to review all published case reports on MRI-induced tattoo complications to identify a possible pattern. So far, 17 cases have been reported. Five (29%) of the cases were in cosmetic tattoos. Symptoms are abrupt and painful with fast onset during MRI, sometimes requiring termination of the procedure. Clinical signs are absent or manifested as inflammation sensed as burning. No thermal skin burns have been recognized. Full recovery is fast, with no sequelae. MRI-induced tattoo complications are uncommon. Patients with cosmetic and traditional tattoos can undergo routine MRI.

AIM To investigate the effect of a glucagon-like peptide-1 receptor agonist (GLP-1RA), liraglutide, on pancreatic volume, oedema, cellularity and DNA synthesis in humans. MATERIALS AND METHODS We performed an open-label study in 14 obese men (age 38 ± 11 years, body mass index 32 ± 4 kg/m2 ) without diabetes. Subjects were examined at baseline, during titration (week 4) of liraglutide towards 3.0 mg/day, and 2 weeks after steady-state treatment (week 6) of a final dose of liraglutide. The primary endpoint was pancreatic volume determined by magnetic resonance imaging. Secondary endpoints included pancreatic oedema and cellularity, positron emission tomography-based [18 F]fluorothymidine (FLT) uptake (DNA synthesis) and plasma pancreatic enzymes. RESULTS Plasma amylase (+7 U/L [95% confidence intervals 3-11], P

Background: Gene electrotrotransfer describes the use of electric pulses to transfer DNA to cells. Particularly skeletal muscle has potential for systemic secretion of therapeutic proteins. Gene electrotransfer to muscle using the integrin inhibitor plasmid AMEP (Antiangiogenic MEtargidin Peptide) was investigated in a phase I dose escalation study. Primary objective was safety. Material and methods: Patients with metastatic or locally advanced solid tumors, without further standard treatments available, were treated with once-only gene electrotransfer of plasmid AMEP to the femoral muscle. Safety was monitored by adverse events registration, visual analog scale (VAS) after procedure and magnetic resonance imaging (MRI) of treated muscles. Pharmacokinetics of plasmid AMEP in plasma and urine was determined by quantitative polymerase chain reaction. Response was evaluated by positron emission tomography–computed tomography (PET–CT) scans. Results: Seven patients were enrolled and treated at dose levels from 50 to 250 μg of plasmid AMEP, the study was terminated early due to cessation of plasmid production. Minimal systemic toxicity was observed and only transient mild pain was associated with the delivery of the electric pulses. MRI of the treated muscles revealed discrete intramuscular edema 24 h after treatment. The changes in the muscle tissue resolved within 2 weeks after treatment. Peak concentrations of plasmid AMEP was detected only in plasma within the first 24 hours after injection. Protein AMEP could not be detected, which could be due to the limit of detection. No objective responses were seen. Conclusions: Gene electrotransfer of plasmid AMEP was found to be safe and tolerable. No objective responses were observed but other DNA drugs may be tested in the future using this procedure.

An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later. In this prospective study we investigated the apparent diffusion coefficient (ADC), perfusion fraction and pseudo diffusion coefficient derived from diffusion weighted MRI as potential early biomarkers for radiotherapy response of brain metastases. It was a particular aim to assess the optimal time point for acquiring the DW-MRI scan during the course of treatment, since to our knowledge this important question has not been addressed directly in previous studies. Twenty-nine metastases (N = 29) from twenty-one patients, treated with whole-brain fractionated external beam RT were analyzed. Patients were scanned with a 1 T MRI system to acquire DW-, T2*W-, T2W- and T1W scans, before start of RT, at each fraction and at follow up two to three months after RT. The DW-MRI parameters were derived using regions of interest based on high b-value images (b = 800 s mm-2). Both volumetric and RECIST criteria were applied for response evaluation. It was found that in non-responding metastases the mean ADC decreased and in responding metastases it increased. The volume based response proved to be far more consistently predictable by the ADC change found at fraction number 7 and later, compared to the linear response (RECIST). The perfusion fraction and pseudo diffusion coefficient did not show sufficient prognostic value with either response assessment criteria. In conclusion this study shows that the ADC derived using high b-values may be a reliable biomarker for early assessment of radiotherapy response for brain metastases patients. The earliest response stratification can be achieved using two DW-MRI scans, one pre-treatment and one at treatment day 7-9 (equivalent to 21 Gy).

Rationale Tumor biopsy cannot detect heterogeneity and an association between heterogeneity in functional imaging and molecular biology will have an impact on both diagnostics and treatment possibilities. Purpose Multiparametric imaging can provide 3D information on functional aspects of a tumor and may be suitable for predicting intratumor heterogeneity. Here, we investigate the correlation between intratumor heterogeneity assessed with multiparametric imaging and multiple-biopsy immunohistochemistry. Methods In this prospective study, patients with primary or recurrent head and neck squamous cell carcinoma (HNSCC) underwent PET/MRI scanning prior to surgery. Tumors were removed en bloc and six core biopsies were used for immunohistochemical (IHC) staining with a predefined list of biomarkers: p40, p53, EGFR, Ki-67, GLUT1, VEGF, Bcl-2, CAIX, PD-L1. Intratumor heterogeneity of each IHC biomarker was quantified by calculating the coefficient of variation (CV) in tumor proportion score among the six core biopsies within each tumor lesion. The heterogeneity in the imaging biomarkers was assessed by calculating CV in 18F-fluorodeoxyglucose (FDG)-uptake, diffusion and perfusion. Concordance of the two variance measures was quantified using Spearman’s rank correlation Results Twenty-eight patients with a total of 33 lesions were included. There was considerable heterogeneity in most of the IHC biomarkers especially in GLUT1, PD-L1, Ki-67, CAIX and p53, however we only observed a correlation between the heterogeneity in GLUT1 and p53 and between Ki-67 and EGFR. Heterogeneity in FDG uptake and diffusion correlated with heterogeneity in cell density. Conclusion Considerable heterogeneity of IHC biomarkers was found, however, only few and weak correlations between the studied IHC markers were observed. The studied functional imaging biomarkers showed weak associations with heterogeneity in some of the IHC biomarkers. Thus, biological heterogeneity is not a general tumor characteristic but depends on the specific biomarker or imaging modality.

Brain metastases (BM) are the most common intracranial malignancy in adults occurring in 9–17% of all cancer patients [1]. The efficacy of current standard of care needs to be improved but toxicity...

Positron emission tomography (PET)/magnetic resonance imaging (MRI) is a new modality that has showed promising results for various clinical indications. Currently, evaluation of neoadjuvant therapy (NT) among patients with adenocarcinoma of the esophagogastric junction has primarily been reserved for PET/computed tomography. Our aim was to evaluate if early response evaluation by PET/MRI is a feasible method to predict resectability. Patients with untreated adenocarcinoma of the esophagogastric junction (Siewert types I/II) and fit for NT with no contraindications for PET/MRI were considered eligible. A baseline scan was performed prior to NT induction and an evaluation scan 3 weeks later. For histopathological response evaluation, the Mandard tumor regression grade score was applied. Response on PET/MRI was evaluated with Response Evaluation Criteria in Solid Tumors (RECIST 1.1), and change in ADC and SUVmax values. Twenty-eight patients were enrolled, and 22 completed both scans and proceeded to final analyses. Seventeen patients were found resectable versus five who were found unresectable. PET/MRI response evaluation had a sensitivity 94%, specificity 80%, and AUC = 0.95 when predicting resectability in patients with adenocarcinoma of the esophagogastric junction. No association with histopathological response (tumor regression grade) was found nor was RECIST correlated with resectability. Response evaluation using PET/MRI was a feasible method to predict resectability in patients with adenocarcinoma of the esophagogastric junction in this pilot study. However, larger studies are warranted to justify the use of the modality for this indication.

Alterations in the gut microbiome have been associated with inflammation and increased cardiovascular risk in HIV-infected individuals. The aim of this study was to investigate the effects of the probiotic strain Lactobacillus rhamnosus GG (LGG) on intestinal inflammation, gut microbiota composition, and systemic markers of microbial translocation and inflammation in HIV-infected individuals.This prospective, clinical interventional trial included 45 individuals [15 combination antiretroviral treatment (cART) naive and 30 cART treated] who ingested LGG twice daily at a dosage of 6 × 109 colony-forming units per capsule for a period of 8 weeks. Intestinal inflammation was assessed using F-2-fluoro-2-deoxy-D-glucose positron emission tomography/magnetic resonance imaging (F-FDG PET/MRI) scans in 15 individuals. Gut microbiota composition (V3-V4 region of the 16s rRNA gene) and markers of microbial translocation and inflammation (lipopolysaccharide, sCD14, sCD163, sCD25, high-sensitive CRP, IL-6, and tumor necrosis factor-alpha) were analyzed at baseline and after intervention.At baseline, evidence of intestinal inflammation was found in 75% of the participants, with no significant differences between cART-naive and cART-treated individuals. After LGG supplementation, a decrease in intestinal inflammation was detected on PET/MRI (-0.3 mean difference in the combined activity grade score from 6 regions, P = 0.006), along with a reduction of Enterobacteriaceae (P = 0.018) and Erysipelotrichaceae (P = 0.037) in the gut microbiome, with reduced Enterobacteriaceae among individuals with decreased F-FDG uptake on PET/MRI (P = 0.048). No changes were observed for soluble markers of microbial translocation and inflammation.A decrease in intestinal inflammation was found in HIV-infected individuals after ingestion of LGG along with a reduced abundance of Enterobacteriaceae, which may explain the local anti-inflammatory effect in the gut.

Background Electrochemotherapy is an established treatment for cutaneous tumors. This study aimed at determining efficacy of electrochemotherapy in recurrent head and neck cancer. Methods Phase II clinical trial in patients with recurrent head and neck carcinomas with no curative treatment options. Electrochemotherapy was performed under general anesthesia. Primary endpoint was tumor response (CT scanning) evaluated at week 8. Secondary endpoints included biopsy results, MRI and fluorodeoxyglucose-positron emission tomography scanning, safety, toxicity, pain score, and quality-of-life questionnaires. Results Of 26 patients treated, 5 (19%) achieved complete response, 10 (39%) partial response, resulting in an objective response of 58%. Two responders remain without recurrence. No serious adverse events occurred during treatment. Four events occurred posttreatment: one bleeding episode, two episodes with mucosal swelling, and one patient died due to disease progression. Conclusion Electrochemotherapy is efficient against local recurrence of head and neck cancer with an overall response rate of 58%.

Purpose The aim of the study was to investigate the components of day-to-day variability of repeated phase contrast mapping (PCM) magnetic resonance imaging measurements of global cerebral blood flow (gCBF). Materials and methods Two dataset were analyzed. In Dataset 1 duplicated PCM measurements of total brain flow were performed in 11 healthy young volunteers on two separate days applying a strictly standardized setup. For comparison PCM measurements obtained from a previously published study (Dataset 2) were analyzed in order to assess long-term variability in an aged population in a less strictly controlled setup. Global CBF was calculated by normalizing total brain flow to brain volume. On each day measurements of hemoglobin, caffeine and glucose were obtained. Linear mixed models were applied to estimate coefficients of variation (CV) of total (CVt), between-subject (CVb), within-subject day-to-day (CVw), and intra-session residual variability (CVr). Results In Dataset 1 CVt, CVb, CVw and CVr were estimated to be 11%, 9.4%, 4% and 4.2%, respectively, and to 8.8%, 7.2%, 2.7% and 4.3%, respectively, when adjusting for hemoglobin and plasma caffeine. In Dataset 2 CVt, CVb and CVw were estimated to be 25.4%, 19.2%, and 15.0%, respectively, and decreased to 16.6%, 8.2% and 12.5%, respectively, when adjusting for the same covariates. Discussion Our results suggest that short-term day-to-day variability of gCBF is relatively low compared to between-subject variability when studied in standardized conditions, whereas long-term variability in an aged population appears to be much larger when studied in less a standardized setup. The results further showed that from 20% to 35% of the total variability in gCBF can be attributed to the effects of hemoglobin and caffeine.

BACKGROUND Tattooed persons examined with magnetic resonance imaging (MRI) can develop burning sensation suggested in the literature to be thermal burn from the procedure. MRI-induced thermal effect and magnetic behavior of known tattoo pigments were examined ex vivo. MATERIALS AND METHODS Magnetic resonance imaging effects on 3 commonly used commercial ink stock products marketed for cosmetic tattooing was studied. A main study tested 22 formulations based on 11 pigment raw materials, for example, one line of 11 called pastes and another called dispersions. Samples were spread in petri dishes and tested with a 0.97 T neodymium solid magnet to observe visual magnetic behavior. Before MRI, the surface temperature of the ink was measured using an infrared probe. Samples were placed in a clinical 3T scanner. Two scans were performed, that is, one in the isocenter and one 30 cm away from the center. After scanning, the surface temperature was measured again. Chemical analysis of samples was performed by mass spectroscopy. RESULTS Mean temperature increase measured in the isocenter ranged between 0.14 and 0.26°C (P

The purpose of this study was to investigate and assess the correlation and reproducibility of multiparametric imaging in head and neck cancer patients. Methods: Twenty-one patients were included in this prospective scan–rescan study. All patients were scanned twice on an integrated PET and MRI scanner. Gross tumor volumes were defined on T2-weighted MR images, and volumes of interest were defined on diffusion-weighted MRI and 18F-FDG PET (VOIDWI, VOIPET). Overlap between volumes was assessed as a percentwise overlap. 18F-FDG uptake and diffusion were measured using SUV and apparent diffusion coefficient, and correlation was tested across and within patients and as a voxel-by-voxel analysis. Results: Seventeen patients were available for correlation analysis, and 12 patients were available for assessment of tumor overlap. The median tumor overlap between VOIDWI and VOIPET was 82% (VOIDWI in VOIPET) and 62% (VOIPET in VOIDWI) on scan 1 and scan 2, respectively. Across patients, the correlation between SUV and apparent diffusion coefficient was weak and nonsignificant. However, in individual patients a weak but significant correlation was identified on a voxel-by-voxel basis. Conclusion: In multiparametric imaging with the integrated PET/MR scanner, the VOIs from DWI and 18F-FDG PET were both within the target volume for radiotherapy and overlapped substantially although not completely. No correlation between 18F-FDG uptake and DWI could be found across patients, but within individual patients a statistically significant, but weak, voxel-by-voxel correlation was found. The findings suggest that information on glucose uptake and diffusion coefficient carries complementary information of interest that may be relevant for radiotherapy treatment planning.

Purpose To evaluate the effect of capecitabine and oxaliplatin before, during, and after radiotherapy for high-risk rectal cancer. Patients and Methods Patients with rectum cancer T4 or T3 involving the mesorectal fascia was included in a prospective phase 2 trial. Liver or lung metastases were accepted if the surgeons found them resectable. The patients received 6 weeks of capecitabine and oxaliplatin before chemoradiotherapy (CRT), continued capecitabine and oxaliplatin during radiotherapy, and received 4 weeks of capecitabine and oxaliplatin after CRT. The patients received radiotherapy as intensity-modulated radiotherapy. Total mesorectal excision was planned 8 weeks after CRT. The patients were evaluated with magnetic resonance imaging (MRI) before start of treatment, after 6 weeks of chemotherapy, and again just before the operation. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-CR29 scoring system was used to evaluate adverse events. Results Fifty-two patients were enrolled between 2009 and 2012. The treatment was well tolerated, with only one death during treatment. Eighty percent of assessable patients experienced response to chemotherapy alone as evaluated by MRI, which increased to 94% after complete oncologic treatment. Forty-nine patients had a total mesorectal excision performed, all with a R0 resection and with a pathologic complete response of 20% for patients with T3 tumor and 7% for patients with T4 tumor. Five patients had metastases at study entry, while 47 patients had locally advanced rectal cancer without metastases. Of these 47 patients, overall survival and progression-free survival at 5 years was 72% and 62%, respectively, with a median follow-up of 60 months. Conclusion This aggressive approach with capecitabine and oxaliplatin before, during, and after radiotherapy for high-risk rectal cancer is safe and feasible; it also has an impressive response rate as measured by MRI and a promising 5-year overall survival.

Meningiomas in children are rare, infrequently described in the literature, and often associated with neurofibromatosis Type 2 (NF2). The authors report a series of 22 children treated for an intracranial meningioma in Denmark between 1935 and 1984.Of 1542 cases of pediatric intracranial tumors in children younger than 15 years of age, 22 harbored meningiomas. Three children suffered from NF. The male/female ratio was 8:14. The mean age at the time of diagnosis was 5 years for boys and 11.5 years for girls. At the time of diagnosis all tumors were large. All patients underwent surgery. In 20 cases, the final histological diagnoses were low-grade and in two cases high-grade tumors. The follow-up period ranged from I to 45 years (mean 16 years). Two patients were lost to follow up. Four of seven boys and three of 13 girls survived. Five of 13 children in whom the tumor was completely removed survived, whereas two of seven in whom the lesion was partially removed survived. The mean survival time in children who died during follow up was 10 years. Two children with anaplastic meningioma remain alive.The long-term prognosis for surgically treated children with intracranial meningiomas was worse than expected. Some reasons for this may have been the late diagnosis and related large size of the tumor during a period of limited diagnostic capacity prior to the computerized tomography and magnetic resonance imaging eras, and the association of NF2 with multiple tumors of the central nervous system. Complete resection is not always possible and should be performed as an image-guided operation.

Background. Although diffusion-weighted magnetic resonance imaging (DW-MRI) is widely used in radiation therapy (RT) response studies, no standard of delineating the region of interest (ROI) exists. In this retrospective study, we evaluate the effect of four ROI strategies on the apparent diffusion coefficients (ADC) in patients receiving palliative RT to brain metastases.Material and methods. Twenty-two metastases from nine patients, treated with whole-brain irradiation (30 Gy in 10 fractions) were analyzed. Patients were scanned with a 1T MR system to acquire DW- (eight b-values), T2*W-, T2W- and T1W scans, before start of RT (pre-RT) and at the 9th/10th fraction (end-RT). The following ROI strategies were applied. ROIb800 and ROIb0: Entire tumor volume visible on DW(b = 800 s/mm2) and DW(b = 0 s/mm2) images, respectively. ROIb800vi: Viable tumor volume based on DW(b = 800 s/mm2). ROIb800rep: ROIb800 from pre-RT scan replicated to end-RT scan. Delineations were aided by co-registered T1W, T2W and T2*W images. ADC was estimated with two mono-exponential fits and one bi-exponential fit.Results. Differences in absolute ADC values were non-significant across ROI strategy independent of fitting method, while significantly different between fitting methods. Evaluation of individual metastases showed that ROI strategies disagreed on the relative ADC change (from pre-RT to end-RT) in 13 of the 22 metastases when all fitting methods were added up.Conclusion. The ROI strategies have an effect on the relative ADC change, which may be important for the assessment of individual patient's response to RT and the interpretation of the current literature.

We compared morphologic computed tomography (CT)-based to metabolic fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/CT-based response evaluation in patients with metastatic colorectal cancer and correlated the findings with survival and KRAS status. From 2006 to 2009, patients were included in a phase II trial and treated with cetuximab and irinotecan every second week. They underwent FDG-PET/CT examination at baseline and after every fourth treatment cycle. Response evaluation was performed prospectively according to Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and retrospectively according to Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Best overall responses were registered. Sixty-one patients were eligible for response evaluation. Partial response (PR) rate was 18%, stable disease (SD) rate 64%, and progressive disease (PD) rate 18%. Partial metabolic response (PMR) rate was 56%, stable metabolic disease rate 33%, and progressive metabolic disease (PMD) rate 11%. Response agreement was poor, κ-coefficient 0.19. Hazard ratio for overall survival for responders (PR/PMR) versus nonresponders (PD/PMD) was higher for CT- than for FDG-PET/CT evaluation. Within patients with KRAS mutations, none had PR but 44% had PMR. In conclusion, morphologic and metabolic response agreement was poor primarily because a large part of the patients shifted from SD with CT evaluation to PMR when evaluated with FDG-PET/CT. Furthermore, a larger fraction of the patients with KRAS mutations had a metabolic treatment response.

It has been suggested that lesions in the insula may result in abnormal electrocardiographic (ECG) findings and increase the risk of sudden death. We investigated if computed tomography (CT) detected insular lesions due to acute stroke were related to ECG abnormalities and mortality at three months. Acute insular lesions were diagnosed in 43/179 patients (left insular = 25; right insular = 17; bilateral = 1) with acute stroke (cerebral infarcts = 62 and intracerebral haemorrhage = 17) based on CT scans from 5-8 days after stroke onset; 12 lead ECGs were recorded on admission and ECG telemetry was done in the first 12-24 hours after admission. Information regarding mortality at three months was obtained. Insular lesions were related to sinus tachycardia with heart rate120 bpm (p = 0.001), ectopic beats10% (p = 0.032), and ST elevation (p = 0.011). Right insular lesions were related to atrial fibrillation (p = 0.009), atrioventricular block (p = 0.029), ectopic beats10% (p = 0.016), and inverted T wave (p = 0.040). Right insular lesions, compared with left or no insular lesions, increased the odds of death within three months (OR 6.2, 95% CI 1.5 to 25.2) independent of stroke severity, lesion volume, and age. As the number of patients in the present study is relatively small, our findings need to be confirmed in studies on other populations of stroke patients.

To assess the consistency of Response Evaluation Criteria in Solid Tumours (RECIST) application in a phase II trial.Patients with metastatic non-resectable colorectal cancer treated with a combination of an antibody and a chemotherapeutic drug, were included. Computed tomography (CT) scans (thorax, abdomen and pelvis) were performed at baseline and after every fourth treatment cycle. RECIST was intended for response evaluation. The scans were consecutively read by a heterogeneous group of radiologists as a part of daily work and hereafter retrospectively reviewed by a dedicated experienced radiologist. Agreement on best overall response (BOR) between readers and reviewer was quantified using κ-coefficients and the discrepancy rate was correlated with the number of different readers per patient using a χ(2)-test.One hundred patients with 396 CT scans were included. Discrepancies between the readers and the reviewer were found in 47 patients. The majority of discrepancies concerned the application of RECIST. With the review, BOR changed in 17 patients, although, only in six patients the change was potentially treatment altering. Overall, the κ-coefficient of agreement between readers and reviewer was 0.71 (good). However, in the subgroup of responding patients the κ-coefficient was 0.21 (fair). The number of patients with discrepancies was significantly higher with three or more different readers per patient than with less (p =0.0003).RECIST was not consistently applied and the majority of the reader discrepancies were RECIST related. Post review, 17 patients changed BOR; six patients in a potentially treatment altering manner. Additionally, we found that the part of patients with discrepancies increased significantly with more than three different readers per patient. The findings support a peer-review approach where a few dedicated radiologists perform double blinded readings of all the on-going cancer trial patients' CT scans.

Measurements of tumour metabolism by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) have been successfully applied to monitor tumour response after chemo- and chemo-radiotherapy and may not have the same limitations as other morphological imaging techniques. In this study it is investigated whether FDG-PET might add information on the efficacy of immune therapy. In a retrospective analysis data from patients with advanced progressive melanoma, treated with DC vaccinations and evaluated by PET/CT scans at baseline as well as after 6 vaccinations were analysed. If a patient achieved stable disease according to RECIST, additional vaccinations were given. The PET scans were evaluated according to EORTC guidelines. PET/CT scans from 13 patients were evaluated. According to RECIST 3 patients achieved stable disease and 10 patients progressed. Interestingly, when evaluated by PET scans 2 patients had partial metabolic response and 1 patient had complete metabolic response of the 2 index lesions even though a new lesion appeared simultaneously. Ten patients were seen to have stable or progressive metabolic disease. By adding PET scans to the CT evaluation of patients treated with DC vaccines, a more detailed picture of the single lesions was found. This seems to improve the clinical evaluation of the treatment. The lack of correlation between the PET and CT scans suggests that some of the increases in target lesions seen in CT scans might be due to oedema or immune-infiltrates and not progression of the disease. Thus, further investigation into the contribution of PET scans to the evaluation of cancer immunotherapy is needed.

The adrenal glucocorticoid stress response in humans causes catabolism, increasing blood glucose and heart rate, and possibly potentiates ischaemic damage to neurons. These effects could induce secondary brain damage in acute stroke.This prospective study was based on a single determination of s-cortisol in 172 patients included within 24 h of stroke onset, 50% within 12 h of stroke onset. All patients were admitted to hospital within 6 h of stroke onset. We investigated the relations of s-cortisol to neurological deficit measured by Scandinavian Stroke Scale (SSS), lesion volume on CT-scan, blood glucose on admission, pulse rate, blood pressure, body temperature, deteriorating stroke, cytokines and cytokine receptors, and outcome.In a multivariate logistic regression analysis, s-cortisol was independently related to death within 7 days of stroke onset, odds ratio (OR) Cortisol(+100 nmol/l) 1.9 (95% CI 1.01-3.8); serum-cortisol was, however, not a predictor of death or dependency within 3 months. S-cortisol correlated to SSS (rho=-0.45, p0.001), body temperature (rho=0.27, p0.001), pulse rate (rho=0.26, p0.001), and lesion volume (rho=0.33, p0.001). S-cortisol was related to the presence of insular damage.Acute stroke mortality related to increasing serum-cortisol levels. S-cortisol was associated with stroke severity and markers reflecting stroke severity.

Background: Serum cardiac troponin I (cTnI) is a specific marker of myocardial injury related to in-patient fatality and cardiac injury in acute stroke. We investigated whether cTnI in acute stroke is related to serum cortisol, acute inflammatory response, and insular damage. We also investigated whether cTnI predicted outcome at 3 months. Patients and Methods: The study was based on 155 patients with CT-confirmed acute cerebral infarction and study inclusion within 24 h (50% within 12 h) of stroke onset. Blood samples were obtained on inclusion. Stroke severity was assessed by the Scandinavian Stroke Scale (SSS) and outcome was assessed by the modified Rankin Scale (mRS), death or dependency was defined as mRS ≧3 three months after stroke. Results: 35% of all patients and 63% of patients who died within 3 months were troponin positive. Tumor necrosis factor-α (TNF-α) and cortisol were independently related to detection of cTnI: TNF-α+100 pg/ml OR 1.5 (CI 95% 1.1–2.2), cortisol+100 nmol/l OR 1.1 (CI 95% 1.01–1.2). SSS and age were also included in this model and did not reach significance. cTnI positivity was, together with age, stroke severity and prestroke mRS, but not s-cortisol, an independent explanatory variable of outcome at 3 months (death or dependency) with OR 4.1 (CI 95% 1.1–14.5). cTnI did not relate to insular involvement. Conclusion: In this study, cortisol and TNF-α were independently related to cTnI, which was predictive of 3-month prognosis.

Although the causes of neurological deterioration in acute cerebral infarction have not yet been identified, many variables have been associated with deterioration. The aim of this study was to investigate deteriorating ischaemic stroke.Deterioration was defined as a decrease in Scandinavian Stroke Scale (SSS) of at least 2 points occurring within 72 h of stroke onset and lasting at least 6 h. The earlier found associations between neurological deterioration and systemic blood pressure, blood glucose, body temperature, stroke severity, and diabetes were investigated in a population of 896 consecutive patients with acute cerebral infarction. In a substudy of 162 of these patients, we evaluated the relations of neurological deterioration to s-ferritin, p-tumor necrosis factor-alpha, p-interleukin-1beta, p-interleukin-1 receptor antagonist, p-interleukin-6, p-interleukin-10, and p-soluble tumor necrosis factor receptors 1 and 2.Patients with neurological deterioration had more severe strokes than nondeteriorating patients: median SSS on admission 31 versus 40, p0.001, Mann-Whitney. We could not confirm previous reports of an association of deteriorating stroke with blood pressure, blood glucose, body temperature, diabetes, s-ferritin or cytokines.Severe stroke was a predictor of neurological deterioration. This study did not confirm other reported predictors of deterioration.

We report a case where tuberculous spondylitis was diagnosed in a 33-year-old man from Greenland. Very typically for Pott's disease, there was back pain, weight loss, and a characteristic kyphotic deformity. Computed tomography showed destruction of the thoracic vertebrae with paraspinal abscesses. The treatment was antituberculous therapy and surgery.

PURPOSE: Solid organ transplant (SOT) recipients are at high risk of developing infections and malignancies.18F-FDG PET/CT may enable timely detection of these diseases and help to ensure early intervention. We aimed to describe the clinical utility of FDG PET/CT in consecutive, diagnostic unresolved SOT recipients transplanted from January 2004 to May 2015.METHODS: Recipients with a post-transplant FDG PET/CT performed as part of diagnostic work-up were included. Detailed chart reviews were done to extract relevant clinical information and determine the final diagnosis related to the FDG PET/CT. Based on á priori defined criteria and the final diagnosis, results from each scan were classified as true or false, and diagnostic values determined.RESULTS: Among the 1,814 recipients in the cohort, 145 had an FDG PET/CT performed; 122 under the indication of diagnostically unresolved symptoms with a suspicion of malignancy or infection. The remaining (N = 23) had an FDG PET/CT to follow-up on a known disease or to stage a known malignancy. The 122 recipients underwent a total of 133 FDG PET/CT scans performed for a suspected malignancy (66 %) or an infection (34 %). Sensitivity, specificity, and positive and negative predictive values of the FDG PET/CT in diagnosing these conditions were 97, 84, 87, and 96 %, respectively.CONCLUSION: FDG PET/CT is an accurate diagnostic tool for the work-up of diagnostic unresolved SOT recipients suspected of malignancy or infection. The high sensitivity and NPV underlines the potential usefulness of PET/CT for excluding malignancy or focal infections in this often complex clinical situation.