The Role of PET Imaging in Patients with Prion Disease: A Literature Review.

Prion diseases are rare, rapidly progressive, and fatal incurable degenerative brain disorders caused by the misfolding of a normal protein called PrPC into an abnormal protein called PrPSc. Their highly variable clinical presentation mimics various degenerative and non-degenerative brain disorders, making diagnosis a significant challenge for neurologists. Currently, definitive diagnosis relies on post-mortem examination of nervous tissue to detect the pathogenic prion protein. The current diagnostic criteria are limited. While structural magnetic resonance imaging (MRI) remains the gold standard imaging modality for Creutzfeldt-Jakob disease (CJD) diagnosis, positron emission tomography (PET) using 18fluorine-fluorodeoxyglucose (18F-FDG) and other radiotracers have demonstrated promising potential in the diagnostic assessment of prion disease. In this context, a comprehensive and updated review exclusively focused on PET imaging in prion diseases is still lacking. We review the current value of PET imaging with 18F-FDG and non-FDG tracers in the diagnostic management of prion diseases. From the collected data, 18F-FDG PET mainly reveals cortical and subcortical hypometabolic areas in prion disease, although fails to identify typical pattern or laterality abnormalities to differentiate between genetic and sporadic prion diseases. Although the rarity of prion diseases limits the establishment of a definitive hypometabolism pattern, this review reveals some more prevalent 18F-FDG patterns associated with each disease subtype. Interestingly, in both sporadic and genetic prion diseases, the hippocampus does not show significant glucose metabolism alterations, appearing as a useful sign in the differential diagnosis with other neurodegenerative disease. In genetic prion disease forms, PET abnormality precedes clinical manifestation. Discordant diagnostic value for amyloid tracers among different prion disease subtypes was observed, needing further investigation. PET has emerged as a potential valuable tool in the diagnostic armamentarium for CJD. Its ability to visualize functional and metabolic brain changes provides complementary information to structural MRI, aiding in the early detection and confirmation of CJD.

Combined 18F-FDG PET-CT markers in dementia with Lewy bodies.

INTRODUCTION: 18F-Fluoro-deoxyglucose-positron emission tomography (FDG-PET) is a supportive biomarker in dementia with Lewy bodies (DLB) diagnosis and its advanced analysis methods, including radiomics and machine learning (ML), were developed recently. The aim of this study was to evaluate the FDG-PET diagnostic performance in predicting a DLB versus Alzheimer's disease (AD) diagnosis. METHODS: FDG-PET scans were visually and semi-quantitatively analyzed in 61 patients. Radiomics and ML analyses were performed, building five ML models: (1) clinical features; (2) visual and semi-quantitative PET features; (3) radiomic features; (4) all PET features; and (5) overall features. RESULTS: At follow-up, 34 patients had DLB and 27 had AD. At visual analysis, DLB PET signs were significantly more frequent in DLB, having the highest diagnostic accuracy (86.9%). At semi-quantitative analysis, the right precuneus, superior parietal, lateral occipital, and primary visual cortices showed significantly reduced uptake in DLB. The ML model 2 had the highest diagnostic accuracy (84.3%). DISCUSSION: FDG-PET is a valuable tool in DLB diagnosis, having visual and semi-quantitative analyses with the highest diagnostic accuracy at ML analyses.

A Young Man with Cognitive Impairment and a Heart Condition.

A 43-year-old came to our observation for progressive cognitive impairment, confirmed by the neuropsychological evaluation. A diagnosis of multidomain amnestic mild cognitive impairment, due to unknown reasons, was posited at the first assessment. The patient's neurological exam was otherwise completely normal. The patient's mother was clinically diagnosed with frontotemporal dementia in her forties. The patient underwent neuroimaging investigations and cerebrospinal fluid analysis. Our diagnostic work-up pointed toward a neurodegenerative etiology, but the presence of concurrent cardiomyopathy emerged in the meantime. Due to the patient's family history, a thorough genetic screening was performed. The results revealed a unique genetic asset, with heterozygotic variants of three amyloid-related genes (PSEN1, APP, and MYBPC3). PSEN1 and MYBPC3 mutations showed distinct pathogenic features and accounted for the patient's brain and cardiac amyloidosis, whereas the APP variant was of uncertain pathological implications.

EEG Abnormalities During Delirium as a Prodromal Feature of Dementia with Lewy Bodies: A Case Report.

Background: A 79-year-old woman was admitted to the Neurology Clinic of the University of Chieti-Pescara for a syncope. At admission, the occurrence of an acute stroke was ruled out. Her cognitive status was unimpaired. After three days from the hospitalization, the patient experienced an episode of mixed delirium. Objective: The present case report shows a case of delirium-onset dementia with Lewy bodies (DLB) with a specific electroencephalographic (EEG) pattern from its prodromal stage. Methods: Delirium was assessed by 4AT test. During the hospitalization, the patient underwent a quantitative EEG (QEEG) with spectral analysis. At six months from the episode of delirium, she was tested by neuropsychological evaluation, QEEG, and 18F-fluorodeoxyglucose PET/CT to assess the onset of a possible cognitive decline. Results: At baseline, the QEEG exam showed a dominant frequency (DF) in the pre-alpha band (7.5 Hz) with a dominant frequency variability (DFV) of 2 Hz. This pattern is typical of DLB at early stage. After six months, she reported attention deficits in association with cognitive fluctuation and REM sleep behavior disorder. The neurological examination revealed signs of parkinsonism. Cognitive status resulted to be impaired (MoCA = 15/30). QEEG recording confirmed the presence of a DLB-typical pattern (DF = 7.5 Hz, DFV = 2.5 Hz). The 18F-FDG-PET/CT showed a moderate bilateral posterior hypometabolism (occipital and temporal cortex), with relative sparing of the posterior cingulate cortex compared to cuneus/precuneus (Cingulate Island sign), and mild bilateral hypometabolism in frontal regions (suggestive of a DLB diagnosis). Conclusion: EEGs may represent supportive and validated biomarkers for delirium-onset prodromal DLB.

Dynamic 11C-Methionine PET-CT: Prognostic Factors for Disease Progression and Survival in Patients with Suspected Glioma Recurrence.

PURPOSE: The prognostic evaluation of glioma recurrence patients is important in the therapeutic management. We investigated the prognostic value of 11C-methionine PET-CT (MET-PET) dynamic and semiquantitative parameters in patients with suspected glioma recurrence. METHODS: Sixty-seven consecutive patients who underwent MET-PET for suspected glioma recurrence at MR were retrospectively included. Twenty-one patients underwent static MET-PET; 46/67 underwent dynamic MET-PET. In all patients, SUVmax, SUVmean and tumour-to-background ratio (T/B) were calculated. From dynamic acquisition, the shape and slope of time-activity curves, time-to-peak and its SUVmax (SUVmaxTTP) were extrapolated. The prognostic value of PET parameters on progression-free (PFS) and overall survival (OS) was evaluated using Kaplan-Meier survival estimates and Cox regression. RESULTS: The overall median follow-up was 19 months from MET-PET. Recurrence patients (38/67) had higher SUVmax (p = 0.001), SUVmean (p = 0.002) and T/B (p < 0.001); deceased patients (16/67) showed higher SUVmax (p = 0.03), SUVmean (p = 0.03) and T/B (p = 0.006). All static parameters were associated with PFS (all p < 0.001); T/B was associated with OS (p = 0.031). Regarding kinetic analyses, recurrence (27/46) and deceased (14/46) patients had higher SUVmaxTTP (p = 0.02, p = 0.01, respectively). SUVmaxTTP was the only dynamic parameter associated with PFS (p = 0.02) and OS (p = 0.006). At univariate analysis, SUVmax, SUVmean, T/B and SUVmaxTTP were predictive for PFS (all p < 0.05); SUVmaxTTP was predictive for OS (p = 0.02). At multivariate analysis, SUVmaxTTP remained significant for PFS (p = 0.03). CONCLUSION: Semiquantitative parameters and SUVmaxTTP were associated with clinical outcomes in patients with suspected glioma recurrence. Dynamic PET-CT acquisition, with static and kinetic parameters, can be a valuable non-invasive prognostic marker, identifying patients with worse prognosis who require personalised therapy.

Biomarker-based stability in limbic-predominant amnestic mild cognitive impairment.

BACKGROUND: The amnestic presentation of mild cognitive impairment (aMCI) represents the most common prodromal stage of Alzheimer's disease (AD) dementia. There is, however, some evidence of aMCI with typical amnestic syndrome but showing long-term clinical stability. The ability to predict stability or progression to dementia in the aMCI condition is important, particularly for the selection of candidates in clinical trials. We aimed to establish the role of in vivo biomarkers, as assessed by cerebrospinal fluid (CSF) measures and [18 F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging, in predicting prognosis in a large aMCI cohort. METHODS: We conducted a retrospective study, including 142 aMCI subjects who had a long follow-up (4-19 years), baseline CSF data and [18 F]FDG-PET scans individually assessed by validated voxel-based procedures, classifying subjects into either limbic-predominant or AD-like hypometabolism patterns. RESULTS: The two aMCI cohorts were clinically comparable at baseline. At follow-up, the aMCI group with a limbic-predominant [18 F]FDG-PET pattern showed clinical stability over a very long follow-up (8.20 ± 3.30 years), no decline in Mini-Mental State Examination score, and only 7% conversion to dementia. Conversely, the aMCI group with an AD-like [18 F]FDG-PET pattern had a high rate of dementia progression (86%) over a shorter follow-up (6.47 ± 2.07 years). Individual [18 F]FDG-PET hypometabolism patterns predicted stability or conversion with high accuracy (area under the curve = 0.89), sensitivity (0.90) and specificity (0.89). In the limbic-predominant aMCI cohort, CSF biomarkers showed large variability and no prognostic value. CONCLUSIONS: In a large series of clinically comparable subjects with aMCI at baseline, the specific [18 F]FDG-PET limbic-predominant hypometabolism pattern was associated with clinical stability, making progression to AD very unlikely. The identification of a biomarker-based benign course in aMCI subjects has important implications for prognosis and in planning clinical trials.

Usefulness of Brain Positron Emission Tomography with Different Tracers in the Evaluation of Patients with Idiopathic Normal Pressure Hydrocephalous.

Idiopathic normal pressure hydrocephalus (iNPH) is the only form of dementia that can be cured by surgery. Its diagnosis relies on clinical and radiological criteria. Identifying patients who can benefit from surgery is challenging, as other neurological diseases can be concomitant or mimic iNPH. We performed a systematic review on the role of positron emission tomography (PET) in iNPH. We retrieved 35 papers evaluating four main functional aspects with different PET radiotracers: (1) PET with amyloid tracers, revealing Alzheimer's disease (AD) pathology in 20-57% of suspected iNPH patients, could be useful in predictions of surgical outcome. (2) PET with radiolabeled water as perfusion tracer showed a global decreased cerebral blood flow (CBF) and regional reduction of CBF in basal ganglia in iNPH; preoperative perfusion parameters could predict surgical outcome. (3) PET with 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG ) showed a global reduction of glucose metabolism without a specific cortical pattern and a hypometabolism in basal ganglia; [18F]FDG PET may identify a coexisting neurodegenerative disease, helping in patient selection for surgery; postsurgery increase in glucose metabolism was associated with clinical improvement. (4) Dopaminergic PET imaging showed a postsynaptic D2 receptor reduction and striatal upregulation of D2 receptor after treatment, associated with clinical improvement. Overall, PET imaging could be a useful tool in iNPH diagnoses and treatment response.

68Ga-DOTATATE and 123I-mIBG as imaging biomarkers of disease localisation in metastatic neuroblastoma: implications for molecular radiotherapy.

PURPOSE: Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) and lutetium-177-labelled DOTATATE (Lu-DOTATATE) are used for molecular radiotherapy of metastatic neuroblastoma. These are taken up by the noradrenaline transporter (NAT) and the somatostatin receptor subtype 2 (SSTR-2), respectively. Scintigraphy of iodine-123-labelled meta-iodobenzylguanidine (I-mIBG) and gallium-68 DOTATATE (Ga-DOTATATE) PET are used to select patients for therapy. These demonstrate the extent and location of tumour, and avidity of uptake by cells expressing NAT and SSTR-2, respectively. This study compared the similarities and differences in the anatomical distribution of these two imaging biomarkers in an unselected series of patients with metastatic neuroblastoma undergoing assessment for molecular radiotherapy. METHODS: Paired whole-body planar I-mIBG views and Ga-DOTATATE maximum intensity projection PET scans of metastatic neuroblastoma patients were visually compared. The disease extent was assessed by a semiquantitative scoring method. RESULTS: Paired scans from 42 patients were reviewed. Ga-DOTATATE scans were positive in all patients, I-mIBG scans were negative in two. In two patients, there was a mismatch, with some lesions identified only on the I-mIBG scan, and others visible only on the Ga-DOTATATE scan. CONCLUSION: Ga-DOTATATE and I-mIBG scans yield complementary information. For a more comprehensive assessment, consideration could be given to the use of both I-mIBG and Ga-DOTATATE imaging scans. Because of the heterogeneity of distribution of molecular targets revealed by these techniques, a combination of both I-mIBG and Lu-DOTATATE molecular radiotherapy may possibly be more effective than either alone.

Atypical Presentation of COVID-19 Incidentally Detected at 18F-FDG PET/CT in an Asymptomatic Oncological Patient.

The incidence of COVID-19, a severe acute respiratory syndrome caused by SARS-CoV-2, is rapidly growing worldwide. In this pandemic period, the chance of incidental pulmonary findings suggestive of COVID-19 at F-FDG PET/CT in asymptomatic oncological patients is not negligible. To suspect COVID-19 is more demanding whether its presentation is atypical. We describe the incidental PET/CT detection of an F-FDG-avid isolated centrilobular pulmonary consolidation in an asymptomatic lymphoma patient, which later resulted in an unexpected and atypical COVID-19 presentation. The nuclear medicine physicians should be prepared to suspect COVID-19 even in asymptomatic patients presenting with a "far-from-COVID-19" finding at PET/CT.

The Additional Value of 18F-FDG PET and MRI in Patients with Glioma: A Review of the Literature from 2015 to 2020.

AIM: Beyond brain computed tomography (CT) scan, Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) hold paramount importance in neuro-oncology. The aim of this narrative review is to discuss the literature from 2015 to 2020, showing advantages or complementary information of fluorine-18 fluorodeoxyglucose (18F-FDG) PET imaging to the anatomical and functional data offered by MRI in patients with glioma. METHODS: A comprehensive Pubmed/MEDLINE literature search was performed to retrieve original studies, with a minimum of 10 glioma patients, published from 2015 until the end of April 2020, on the use of 18F-FDG PET in conjunction with MRI. RESULTS: Twenty-two articles were selected. Combined use of the two modalities improves the accuracy in predicting prognosis, planning treatments, and evaluating recurrence. CONCLUSION: According to the recent literature, 18F-FDG PET provides different and complementary information to MRI and may enhance performance in the whole management of gliomas. Therefore, integrated PET/MRI may be particularly useful in gliomas, since it could provide accurate morphological and metabolic information in one-shoot examination and improve the diagnostic value compared to each of procedures.

Reliability of intraoperative ultrasound in detecting tumor residual after brain diffuse glioma surgery: a systematic review and meta-analysis.

Intraoperative ultrasonography (iUS) is considered an accurate, safe, and cost-effective tool to estimate the extent of resection of both high-grade (HGG) and low-grade (DLGG) diffuse gliomas (DGs). However, it is currently missing an evidence-based assessment of iUS diagnostic accuracy in DGs surgery. The objective of review is to perform a systematic review and meta-analysis of the diagnostic performance of iUS in detecting tumor residue after DGs resection. A comprehensive literature search for studies published through October 2018 was performed according to PRISMA-DTA and STARD 2015 guidelines, using the following algorithm: ("ultrasound" OR "ultrasonography" OR "ultra-so*" OR "echo*" OR "eco*") AND ("brain" OR "nervous") AND ("tumor" OR "tumour" OR "lesion" OR "mass" OR "glio*" OR "GBM") AND ("surgery" OR "surgical" OR "microsurg*" OR "neurosurg*"). Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) of iUS in DGs were calculated. A subgroup analysis for HGGs and DLGGs was also conducted. Thirteen studies were included in the systematic review (665 DGs). Ten articles (409 DGs) were selected for the meta-analysis with the following results: sensitivity 72.2%, specificity 93.5%, LR- 0.29, LR+ 3, and DOR 9.67. Heterogeneity among studies was non-significant. Subgroup analysis demonstrates a better diagnostic performance of iUS for DLGGs compared with HGGs. iUS is an effective technique in assessing DGs resection. No significant differences are seen regarding iUS modality and transducer characteristics. Its diagnostic performance is higher in DLGGs than HGGs and could be worsened by previous treatments, surgical artifacts, and small tumor residue volumes.

Diagnostic Performance and Prognostic Value of PET/CT with Different Tracers for Brain Tumors: A Systematic Review of Published Meta-Analyses.

BACKGROUND: Several meta-analyses reporting data on the diagnostic performance or prognostic value of positron emission tomography (PET) with different tracers in detecting brain tumors have been published so far. This review article was written to summarize the evidence-based data in these settings. METHODS: We have performed a comprehensive literature search of meta-analyses published in the Cochrane library and PubMed/Medline databases (from inception through July 2019) about the diagnostic performance or prognostic value of PET with different tracers in patients with brain tumors. RESULTS: We have summarized the results of 24 retrieved meta-analyses on the use of PET or PET/computed tomography (CT) with different tracers in brain tumors. The tracers included were: fluorine-18 fluorodeoxyglucose (18F-FDG), carbon-11 methionine (11C-methionine), fluorine-18 fluoroethyltyrosine (18F-FET), fluorine-18 dihydroxyphenylalanine (18F-FDOPA), fluorine-18 fluorothymidine (18F-FLT), and carbon-11 choline (11C-choline). Evidence-based data demonstrated good diagnostic performance of PET with different tracers in detecting brain tumors, in particular, radiolabelled amino acid tracers showed the highest diagnostic performance values. All the PET tracers evaluated had significant prognostic value in patients with glioma. CONCLUSIONS: Evidence-based data showed a good diagnostic performance for some PET tracers in specific indications and significant prognostic value in brain tumors.

How Often Do We Fail to Classify the Treatment Response with [18F]FDG PET/CT Acquired on Different Scanners? Data from Clinical Oncological Practice Using an Automatic Tool for SUV Harmonization.

PURPOSE: Tumor response evaluated by 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) with standardized uptake value (SUV) is questionable when pre- and post-treatment PET/CT are acquired on different scanners. The aims of our study, performed in oncological patients who underwent pre- and post-treatment [18F]FDG PET/CT on different scanners, were (1) to evaluate whether EQ·PET, a proprietary SUV inter-exams harmonization tool, modifies the EORTC tumor response classification and (2) to assess which classification (harmonized and non-harmonized) better predicts clinical outcome. PROCEDURES: We retrospectively identified 95 PET pairs (pre- and post-treatment) performed on different scanners (Biograph mCT, Siemens; GEMINI GXL, Philips) in 73 oncological patients (52F; 57.8 ± 16.3 years). An 8-mm Gaussian filter was applied for the Biograph protocol to meet the EANM/EARL harmonization standard; no filter was needed for GXL. SUVmax and SUVmaxEQ of the same target lesion in the pre- and post-treatment PET/CT were noted. For each PET pair, the metabolic response classification (responder/non-responder), derived from combining the EORTC response categories, was evaluated twice (with and without harmonization). In discordant cases, the association of each metabolic response classification with final clinical response assessment and survival data (2-year disease-free survival, DFS) was assessed. RESULTS: On Biograph, SUVmaxEQ of all target lesions was significantly lower (p = 0.001) than SUVmax (8.5 ± 6.8 vs 12.5 ± 9.6; - 38.6 %). A discordance between the two metabolic response classifications (harmonized and non-harmonized) was found in 19/95 (20 %) PET pairs. In this subgroup (n = 19; mean follow-up, 33.9 ± 9 months), responders according to harmonized classification (n = 9) had longer DFS (47.5 months, 88.9 %) than responders (n = 10) according to non-harmonized classification (26.3 months, 50.0 %; p = 0.01). Moreover, harmonized classification showed a better association with final clinical response assessment (17/19 PET pairs). CONCLUSIONS: The harmonized metabolic response classification is more associated with the final clinical response assessment, and it is able to better predict the DFS than the non-harmonized classification. EQ·PET is a useful harmonization tool for evaluating metabolic tumor response using different PET/CT scanners, also in different departments or for multicenter studies.

The kinetics of 18F-FDG in lung cancer: compartmental models and voxel analysis.

BACKGROUND: The validation of the most appropriate compartmental model that describes the kinetics of a specific tracer within a specific tissue is mandatory before estimating quantitative parameters, since the behaviour of a tracer can be different among organs and diseases, as well as between primary tumours and metastases. The aims of our study were to assess which compartmental model better describes the kinetics of 18F-Fluorodeoxygluxose(18F-FDG) in primary lung cancers and in metastatic lymph nodes; to evaluate whether quantitative parameters, estimated using different innovative technologies, are different between lung cancers and lymph nodes; and to evaluate the intra-tumour inhomogeneity. RESULTS: Twenty-one patients (7 females; 71 ± 9.4 years) with histologically proved lung cancer, prospectively evaluated, underwent 18F-FDG PET-CT for staging. Spectral analysis iterative filter (SAIF) method was used to design the most appropriate compartmental model. Among the compartmental models arranged using the number of compartments suggested by SAIF results, the best one was selected according to Akaike information criterion (AIC). Quantitative analysis was performed at the voxel level. K1, Vb and Ki were estimated with three advanced methods: SAIF approach, Patlak analysis and the selected compartmental model. Pearson's correlation and non-parametric tests were used for statistics. SAIF showed three possible irreversible compartmental models: Tr-1R, Tr-2R and Tr-3R. According to well-known 18F-FDG physiology, the structure of the compartmental models was supposed to be catenary. AIC indicated the Sokoloff's compartmental model (3K) as the best one. Excellent correlation was found between Ki estimated by Patlak and by SAIF (R2 = 0.97, R2 = 0.94, at the global and the voxel level respectively), and between Ki estimated by 3K and by SAIF (R2 = 0.98, R2 = 0.95, at the global and the voxel level respectively). Using the 3K model, the lymph nodes showed higher mean and standard deviation of Vb than lung cancers (p < 0.0014, p < 0.0001 respectively) and higher standard deviation of K1 (p < 0.005). CONCLUSIONS: One-tissue reversible plus one-tissue irreversible compartmental model better describes the kinetics of 18F-FDG in lung cancers, metastatic lymph nodes and normal lung tissues. Quantitative parameters, estimated at the voxel level applying different advanced approaches, show the inhomogeneity of neoplastic tissues. Differences in metabolic activity and in vascularization, highlighted among all cancers and within each individual cancer, confirm the wide variability in lung cancers and metastatic lymph nodes. These findings support the need of a personalization of therapeutic approaches.

Neo-adjuvant platinum-based chemotherapy followed by chemoradiation and radical surgery in locally advanced cervical cancer (Lacc) patients: A phase II study.

PURPOSE: The aim of this Phase II, non-randomized study was to assess activity and safety of neoadjuvant chemotherapy (NACT) before chemoradiation (CT/RT) followed by radical surgery (RS) in locally advanced cervical cancer (LACC) patients. METHODS AND MATERIALS: The primary end point was rate of pathologic complete response (pCR). FIGO Stage IB2-IVA patients were administered NACT chemotherapy (paclitaxel 80 mg/m2, carboplatin AUC 2), for 6 weeks, followed by Intensity Modulated Radiotherapy plus simultaneous boost (total dose of 50.4 Gy to CTV1, and 39.6 Gy to CTV2). Clinical response was assessed according to RECIST criteria. Responsive patients were triaged to RS. The regimen would be considered active if >20 pCRs were registered in 39 patients. RESULTS: 45 patients were enrolled into the study; 25 patients (55.5%) were FIGO stage IIB, 9 cases (20.0%) had stage III disease. At work up, pelvic lymph node involvement was documented in 38 (84.4%) patients; pCR was documented in 18 out of 40 patients (45.0%). Grade 3-4 hematological toxicity after NACT occurred in 4 patients; CT/RT associated grade 3 toxicity was found in 7 patients. Early and late postoperative complications were detected in 16, and 11 cases, respectively. Three-year PFS and OS were 66.0% and 86.0%, respectively. CONCLUSIONS: NACT followed by CT/RT by IMRT and RS, is feasible and safe; failure to achieve the primary endpoint has to be recognized; however, enrollment of a higher rate of poor prognosis patients compared to historical data used to calculate sample size, could have resulted in reduced activity.

Intranasal Nerve Growth Factor administration improves cerebral functions in a child with severe traumatic brain injury: A case report.

BACKGROUND: Nerve growth factor (NGF) promotes neural recovery after experimental traumatic brain injury (TBI) supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated protein Doublecortin (DCX). Only a few studies reported NGF administration in paediatric patients with severe TBI. METHODS: A four-year-old boy in a persistent unresponsive wakefulness syndrome (UWS) was treated with intranasal murine NGF administration 6 months after severe TBI. The patient received four cycles of intranasal NGF (0.1 mg/kg, twice a day for 10 consecutive days). RESULTS: NGF administration improved functional [Positron Emission Tomography/Computed Tomography (PET/CT); Single photon emission/Computed Tomography (SPECT/CT) and Magnetic Resonance Imaging (MRI)] assessment, electrophysiological [Electroencephalogram (EEG) and Visual Evoked Potential (VEP)] studies and clinical conditions. He showed improvements in voluntary movements, facial mimicry, phonation, attention and verbal comprehension, ability to cry, cough reflex, oral motility, feeding capacity, and bowel and urinary functions. After NGF administration, raised levels of both NGF and DCX were found in the cerebrospinal fluid of the patient. No side effects were reported. CONCLUSIONS: Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal NGF administration appears to be a promising and safe rescuing strategy treatment in children with neurological impairment after TBI.

The predictive value of 18F-FDG PET-CT for assessing the clinical outcomes in locally advanced NSCLC patients after a new induction treatment: low-dose fractionated radiotherapy with concurrent chemotherapy.

BACKGROUND: Patients with locally advanced non-small-cell lung cancer (LA-NSCLC) have poor prognosis despite several multimodal approaches. Recently, low-dose fractionated radiotherapy concurrent to the induction chemotherapy (IC-LDRT) has been proposed to further improve the effects of chemotherapy and prognosis. Until now, the predictive value of metabolic response after IC-LDRT has not yet been investigated. AIM: to evaluate whether the early metabolic response, assessed by 18F-fluoro-deoxyglucose positron emission-computed tomography (18F-FDG PET-CT), could predict the prognosis in LA-NSCLC patients treated with a multimodal approach, including IC-LDRT. METHODS: Forty-four consecutive patients (35males, mean age: 66 ± 7.8 years) with stage IIIA/IIIB NSCLC were retrospectively evaluated. Forty-four patients underwent IC-LDRT (2 cycles of chemotherapy, 40 cGy twice daily), 26/44 neo-adjuvant chemo-radiotherapy (CCRT: 50.4Gy), and 20/44 surgery. 18F-FDG PET-CT was performed before (baseline), after IC-LDRT (early) and after CCRT (final), applying PET response criteria in solid tumours (PERCIST). Patients with complete/partial metabolic response were classified as responders; patients with stable/progressive disease as non-responders. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meyer analysis; the relationship between clinical factors and survivals were assessed using uni-multivariate regression analysis. RESULTS: Forty-four out of 44, 42/44 and 23/42 patients underwent baseline, early and final PET-CT, respectively. SULpeak of primary tumour and lymph-node significantly (p = 0.004, p = 0.0002, respectively) decreased after IC-LDRT with a further reduction after CCRT (p = 0.0006, p = 0.02, respectively). At early PET-CT, 20/42 (47.6%) patients were classified as responders, 22/42 (52.3%) as non-responders. At final PET-CT, 19/23 patients were classified as responders (12 responders and 7 non-responders at early PET-CT), and 4/23 as non-responders (all non-responders at early PET-CT). Early responders had better PFS and OS than early non-responders (p ≤ 0.01). Early metabolic response was predictive factor for loco-regional, distant and global PFS (p = 0.02, p = 0.01, p = 0.005, respectively); surgery for loco-regional and global PFS (p = 0.03, p = 0.009, respectively). CONCLUSIONS: In LA-NSCLC patients, 18F-FDG metabolic response assessed after only two cycles of IC-LDRT predicts the prognosis. The early evaluation of metabolic changes could allow to personalize therapy. This multimodality approach, including both low-dose radiotherapy that increases the effects of induction chemotherapy, and surgery that removes the disease, improved clinical outcomes. Further prospective investigation of this new induction approach is warranted.

Decompressive craniectomy and hydrocephalus: proposal of a therapeutic flow chart.

Decompressive craniectomy (DC) may be necessary to save the lives of patients suffering from intracranial hypertension. However, this procedure is not complication-free. Its two main complications are hydrocephalus and the sinking skin-flap syndrome (SSFS). The radiological findings and the clinical evaluation may be not enough to decide when and/or how to treat hydrocephalus in a decompressed patient. SSFS and hydrocephalus may be not unrelated. In fact, a patient affected by hydrocephalus, after the ventriculo-peritoneal shunt, can develop SSFS; on the other hand, SSFS per se can cause hydrocephalus. Treating hydrocephalus in decompressed patients can be challenging. Radiological findings and clinical evaluation may not be enough to define the most appropriate therapeutic strategy. Cerebrospinal fluid (CSF) dynamics and metabolic evaluations can represent important diagnostic tools for assessing the need of a CSF shunt in patients with a poor baseline neurologic status. Based on our experience, we propose a flow chart for treating decompressed patients affected by ventriculomegaly.

Endometriosis-associated clear cell carcinoma arising in caesarean section scar: a case report and review of the literature.

BACKGROUND: Malignant transformation has been reported in approximately 1% of the endometriosis cases; herein, we report a case of clear cell endometrial carcinoma arising from endometriosis foci located within a caesarean section scar. CASE PRESENTATION: In November 2014, a Caucasian, 44-year-old woman was transferred to our institution because of severe respiratory failure due to massive lung embolism and rapid enlargement of a subcutaneous suprapubic mass. Abdomino-pelvic magnetic resonance showed a 10.5 × 5.0 × 5.0 cm subcutaneous solid mass involving the rectus abdominis muscle. Pelvic organs appeared normal, while right external iliac lymph nodes appeared enlarged (maximum diameter = 16 mm). A whole-body positron emission tomography/computed tomography scan showed irregular uptake of the radiotracer in the 22 cm mass of the abdominal wall, and in enlarged external iliac and inguinal lymph nodes. In December 2014, the patient underwent exploratory laparoscopy showing normal adnexae and pelvic organs; peritoneal as well as cervical, endometrial and vesical biopsies were negative. The patient was administered neo-adjuvant chemotherapy with carboplatin and paclitaxel, weekly, without benefit and then underwent wide resection of the abdominal mass, partial removal of rectus abdominis muscle and fascia, radical hysterectomy, bilateral salpingo-oophorectomy, and inguinal and pelvic lymphadenectomy. The muscular gap was repaired employing a gore-tex mesh while the external covering was made by a pedicled perforator fasciocutaneous anterolateral thigh flap. Final diagnosis was clear cell endometrial adenocarcinoma arising from endometriosis foci within the caesarean section scar. Pelvic and inguinal lymph nodes were metastatic. Tumor cells were positive for CK7 EMA, CKAE1/AE3, CD15, CA-125, while immunoreaction for Calretinin, WT1, estrogen, and progesterone receptors, cytokeratin 20, CD10, alpha fetoprotein, CDX2, TTF1, and thyroglobulin were all negative. Liver relapse occurred after 2 months; despite 3 cycles of pegylated liposomal doxorubicin (20 mg/m2, biweekly administration), the death of the patient disease occurred 1 month later. CONCLUSIONS: Attention should be focused on careful evaluation of patient history in terms of pelvic surgery, and symptoms suggestive of endometriosis such as repeated occurrence of endometriosis nodules at CS scar, or cyclic pain, or volume changes of the nodules.

Cerebral metabolism and perfusion in MR-negative individuals with refractory focal epilepsy assessed by simultaneous acquisition of (18)F-FDG PET and arterial spin labeling.

The major challenge in pre-surgical epileptic patient evaluation is the correct identification of the seizure onset area, especially in MR-negative patients. In this study, we aimed to: (1) assess the concordance between perfusion, from ASL, and metabolism, from (18)F-FDG, acquired simultaneously on PET/MR; (2) verify the utility of a statistical approach as supportive diagnostic tool for clinical readers. Secondarily, we compared (18)F-FDG PET data from the hybrid PET/MR system with those acquired with PET/CT, with the purpose of validate the reliability of (18)F-FDG PET/MR data. Twenty patients with refractory focal epilepsy, negative MR and a defined electro-clinical diagnosis underwent PET/MR, immediately followed by PET/CT. Standardized uptake value ratio (SUVr) and cerebral blood flow (CBF) maps were calculated for PET/CT-PET/MR and ASL, respectively. For all techniques, z-score of the asymmetry index (zAI) was applied for depicting significant Right/Left differences. SUVr and CBF images were firstly visually assessed by two neuroimaging readers, who then re-assessed them considering zAI for reaching a final diagnosis. High agreement between (18)F-FDG PET/MR and ASL was found, showing hypometabolism and hypoperfusion in the same hemisphere in 18/20 patients, while the remaining were normal. They were completely concordant in 14/18, concordant in at least one lobe in the remaining. zAI maps improved readers' confidence in 12/20 and 15/20 patients for (18)F-FDG PET/MR and ASL, respectively. (18)F-FDG PET/CT-PET/MR showed high agreement, especially when zAI was considered. The simultaneous metabolism-perfusion acquisition provides excellent concordance on focus lateralisation and good concordance on localisation, determining useful complementary information.