We investigated the diagnostic performance of Somatostatin Receptor Positron Emission Tomography/Computed Tomography (SSR-PET/CT) for the detection of primary lesion and initial staging of pancreatic ...neuroendocrine tumors (pNETs). A comprehensive literature search up to January 2020 was performed selecting studies in presence of: sample size ≥10 patients; index test (i.e., 68Ga-DOTATOC or 68Ga-DOTANOC or 68Ga-DOTATATE PET/CT); and outcomes (i.e., detection rate (DR), true positive, true negative, false positive, and false-negative). The methodological quality was evaluated with QUADAS-2. Pooled DR and pooled sensitivity and specificity for the identification of the primary tumor were assessed by a patient-based and a lesion-based analysis. Thirty-eight studies were selected for the qualitative analysis, while 18 papers were included in the meta-analysis. The number of pNET patients ranged from 10 to 142, for a total of 1143 subjects. At patient-based analysis, the pooled sensitivity and specificity for the assessment of primary pNET were 79.6% (95% confidence interval (95%CI): 71–87%) and 95% (95%CI: 75–100%) with a heterogeneity of 59.6% and 51.5%, respectively. Pooled DR for the primary lesion was 81% (95%CI: 65–90%) and 92% (95%CI: 80–97%), respectively, at patient-based and lesion-based analysis. In conclusion, SSR-PET/CT has high DR and diagnostic performances for primary lesion and initial staging of pNETs.
Ewing's sarcoma (EWS), an aggressive pediatric bone and soft-tissue sarcoma, has a very stable genome with very few genetic alterations. Unlike in most cancers, the progression of EWS appears to ...depend on epigenetic alterations. EWS-FLI1 and CD99, the two hallmarks of EWS, are reported to severely impact the malignancy of EWS cells, at least partly by regulating the expression of several types of non-coding RNAs. Here, we identify miR-214-3p as a common mediator of either EWS-FLI1 or CD99 by in silico analysis. MiR-214-3p expression was lower in EWS cells and in clinical samples than in bone marrow mesenchymal stem cells, and this miRNA was barely expressed in metastatic lesions. Silencing of EWS-FLI1 or CD99 restored the expression of miR-214-3p, leading to a reduced cell growth and migration. Mechanistically, miR-214-3p restoration inhibits the expression of the high-mobility group AT-hook 1 (HMGA1) protein, a validated target of miR-214-3p and a major regulator of the transcriptional machinery. The decrease in HMGA1 expression reduced the growth and the migration of EWS cells. Taken together, our results support that the miR-214-3p is constitutively repressed by both EWS-FLI1 and CD99 because it acts as an oncosuppressor limiting the dissemination of EWS cells.
Bevacizumab plus FOLFOX-4 regimen represents the first-line therapy in patients affected by metastatic colorectal cancer (mCRC). Hyperthermia has been considered an effective ancillary treatment for ...cancer therapy through several anti-tumor mechanisms, sharing with Bevacizumab the inhibition of angiogenesis. Up to now, scientific literature offers very few clinical data on the combination of bevacizumab plus oxaliplatin-based chemotherapy with deep electro-hyperthermia (DEHY) for metastatic colon cancer (mCC) patients. Therefore, we aimed at evaluating the efficacy of this combination based on the possible interaction between the DEHY and bevacizumab anti-tumor mechanisms. We conducted a retrospective analysis on 40 patients affected by mCC treated with the combination of bevacizumab plus FOLFOX-4 (fluorouracil/folinic acid plus oxaliplatin) and DEHY (EHY2000), between January 2017 and May 2020. DEHY treatment was performed weekly, with capacitive electrodes at 80–110 W for 50 min, during and between subsequent bevacizumab administrations, on abdomen for liver or abdominal lymph nodes metastases and thorax for lung metastases. Treatment response assessment was performed according to the Response Evaluation Criteria for Solid Tumors (RECIST). The primary endpoints were disease control rate (DCR) and progression-free survival (PFS). The secondary endpoint was overall survival (OS). DCR, counted as the percentage of patients who had the best response rating complete response (CR), partial response (PR), or stable disease (SD), was assessed at 90 days (timepoint-1) and at 180 days (timepoint-2). DCR was 95% and 89.5% at timepoint-1 and timepoint-2, respectively. The median PFS was 12.1 months, whereas the median OS was 21.4 months. No major toxicity related to DEHY was registered; overall, this combination regimen was safe. Our results suggest that the combined treatment of DEHY with bevacizumab plus FOLFOX-4 as first-line therapy in mCC is feasible and effective with a favorable disease control, prolonging PFS of 2.7 months with respect to standard treatment without DEHY for mCC patients. Further studies will be required to prove its merit and explore its potentiality, especially if compared to conventional treatment.
The early identification of patients at risk of complications of infective endocarditis (IE) using parameters obtained as part of routine practice is essential for guiding clinical decision-making. ...This study aimed to identify a parameter at hospital admission that predicts the outcome, adding value to other well-known factors of a poor prognosis in IE.
Two hundred and three patients with IE were included in this study. Clinical evaluation, echocardiography, blood cultures, and routine laboratory tests were performed at hospital admission. The endpoint was in-hospital mortality.
The mean age of the patients was 48.2±16.6 years; 62% were male and 38% had rheumatic heart disease. During treatment, cardiac surgery was performed in 111 patients (55%), and the overall in-hospital mortality rate was 32%. In the multivariable analysis, the independent predictors of death were age (odds ratio (OR) 1.07, 95% confidence interval (CI) 1.02–1.13), C-reactive protein (CRP) at hospital admission (OR 1.12, 95% CI 1.04–1.21), length of the vegetation at diagnosis (OR 1.15, 95% CI 1.03–1.28), development of heart failure (OR 6.43, 95% CI 2.14–19.33), and embolic events during antimicrobial therapy (OR 12.14, 95% CI 2.11–71.89).
An elevated CRP level at hospital admission and vegetation length at diagnosis were strong predictors of in-hospital mortality in IE, independent of other prognostic parameters, specifically taking into account patient characteristics and complications during therapy.
Immunotherapy is a promising therapeutic strategy both for solid and hematologic tumors, such as in Hodgkin (HL) and non-Hodgkin lymphoma (NHL). In particular, immune-checkpoint inhibitors, such as ...nivolumab and pembrolizumab, are increasingly used for the treatment of refractory/relapsed HL. At the same time, evidence of chimeric antigen receptor (CAR)-T-cell immunotherapy efficacy mostly in NHL is growing. In this setting, the challenge is to identify an appropriate imaging method to evaluate immunotherapy response. The role of 18F-Fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT), especially in early evaluation, is under investigation in order to guide therapeutic strategies, taking into account the possible atypical responses (hyperprogression and pseudoprogression) and immune-related adverse events that could appear on PET images. Herein, we aimed to present a critical overview about the role of 18F-FDG PET/CT in evaluating treatment response to immunotherapy in lymphoma patients.
Abstract Background Dedifferentiated chondrosarcoma has a very poor prognosis. Because of its rarity, there are few large studies of outcome which might identify potential prognostic factors. In ...particular there remains uncertainty about the value of chemotherapy for this condition. Method A retrospective study was done using data supplied by members of the European Musculo Skeletal Oncology Society (EMSOS). We obtained data on 337 patients from nine European centres with this rare condition, with details on patients, treatment and outcome which were then analysed in an attempt to identify prognostic features. Results The median age was 59 years and there was a slight predominance of males (53%). The most common sites were the femur and pelvis. Twenty-nine percent of patients with a long bone tumour had a pathological fracture. 71 patients (21%) had metastases at the time of diagnosis and these patients had a median survival of 5 months with a 10% chance of survival at 2 years. For the 266 patients without metastases at diagnosis, 254 underwent surgery with 79% having limb salvage. Thirty-one percent of these 266 patients had chemotherapy with 47% of those under 60 receiving it. In this group of 266 patients, overall survival was 28% at 10 years and poor prognostic factors were the presence of a pathological fracture at diagnosis, a pelvic location and increasing age. Local recurrence and overall survival were related to inadequate margins of excision. We did not find that the histological subtype, size of the tumour or the use of chemotherapy significantly affected outcome. For all patients the overall survival was 24% at 5 years. Conclusions The prognosis for patients with dedifferentiated chondrosarcoma remains dismal. Surgery with clear margins remains the principal treatment for this condition. Further use of chemotherapy should be within a trial or treatment protocol.
Dyspnea is an important symptomatic endpoint for assessment of radiation-induced lung injury (RILI) following radical radiotherapy in locally advanced disease, which remains the mainstay of treatment ...at the time of significant advances in therapy including combination treatments with immunotherapy and chemotherapy and the use of local ablative radiotherapy techniques. We investigated the relationship between dose-volume parameters and subjective changes in dyspnea as a measure of RILI and the relationship to spirometry.
Eighty patients receiving radical radiotherapy for non-small cell lung cancer were prospectively assessed for dyspnea using two patient-completed tools: EORTC QLQ-LC13 dyspnea quality of life assessment and dyspnea visual analogue scale (VAS). Global quality of life, spirometry and radiation pneumonitis grade were also assessed. Comparisons were made with lung dose-volume parameters.
The median survival of the cohort was 26 months. In the evaluable group of 59 patients there were positive correlations between lung dose-volume parameters and a change in dyspnea quality of life scale at 3 months (V
p=0.017; V
p=0.026; V
p=0.049; mean lung dose p=0.05), and a change in dyspnea VAS at 6 months (V
p=0.05; V
p=0.026; V
p=0.028) after radiotherapy. Lung dose-volume parameters predicted a 10% increase in dyspnea quality of life score at 3 months (V
; p=0.041, V
; p=0.037) and dyspnea VAS score at 6 months (V
; p=0.027) post-treatment.
Worsening of dyspnea is an important symptom of RILI. We demonstrate a relationship between lung dose-volume parameters and a 10% worsening of subjective dyspnea scores. Our findings support the use of subjective dyspnea tools in future studies on radiation-induced lung toxicity, particularly at doses below conventional lung radiation tolerance limits.
Nonalcoholic fatty liver disease(NAFLD) has been identified as one of the most prevalent chronic liver disease in adults and children populations. NAFLD is usually associated with the metabolic ...syndrome(MS), which is chiefly related to insulin resistance and its consequences. Insulin resistance has a crucial role in the pathogenesis of hepatic steatosis and potentially nonalcoholic steatohepatitis(NASH). Because of the contemporary epidemics of MS and obesity, the burden of NAFLD is also expected to rise. Unhealthy diets, such as the so-called western diet, are enriched in fructose, trans-fatty acids and saturated fat and seem to be associated with the development of NAFLD. In human studies, certain dietary sugars, particularly fructose, are used as a substrate for lipogenesis leading to hepatic fatty infiltration, inflammation, and possibly fibrosis. Other investigations have shown that fat consumption especially cholesterol and trans/saturated fatty acids are also steatogenic and seem to increase visceral adiposity. The identification of specific dietary components that favor the development of NASH could be important for the management of this disorder. This review focuses on the effects of different dietary approaches to prevent and treat NAFLD emphasizing the macronutrients and energy composition.
The amount of evidence for guideline‐directed new heart failure (HFrEF) disease‐modifying drugs in the context of chronic kidney disease (CKD) is relatively modest, especially in end‐stage CKD. We ...report a case of dramatic reverse remodelling and disease regression in a naïve HFrEF young woman on haemodialysis treated with sacubitril/valsartan and SGLT2i. At 10‐month follow‐up, the patient normalized left ventricle and atrial volumes and improved ejection fraction to the normal range, assessed both by echocardiography and cardiac magnetic resonance. Cardiac biomarkers and exercise performance improved consensually. The haemodialysis protocol and the loop diuretic dose were unchanged within the whole period.
Nowadays, there is still no consensus on the most accurate PET radiopharmaceutical to early detect prostate cancer (PCa) relapse. A tailored radiotracer choice based on a specific patient's profile ...could ensure prompt disease detection and an improvement in patients management. We aimed to compare the
Ffluciclovine and
Ffluorocholine PET/CT detection rate (DR) in PCa patients restaged for early biochemical recurrence (BCR), according to clinical and biochemical features. A cohort of 138 PCa patients with early BCR (mean age: 71 y, range: 50-87 y) were homogeneously randomized 1:1 to a
Ffluciclovine or a
Ffluorocholine PET/CT group. The respective PET/CT DR, according to per-patient and per-region analysis, and the impact of the biochemical, clinical, and histological parameters, were compared. The PSA cut-off values predictive of a positive scan were also calculated. Overall, the
Ffluciclovine PET/CT DR was 64%, significantly higher than the
Ffluorocholine PET/CT DR of 35% (
= 0.001). Similarly, in the per-region analysis, the
Ffluciclovine PET/CT DR was 51% in the prostate region, significantly higher compared to 15% of
Ffluorocholine (
< 0.0001). Furthermore, a statistically significant higher DR in per-patient and per-region (prostate/prostate bed) analysis was observed in the
Ffluciclovine group for 0.5-1 ng/mL (
= 0.018,
= 0.049) and >1 ng/mL (
= 0.040,
< 0.0001) PSA values. A PSA of 0.45 ng/mL for
Ffluciclovine and of 0.94 ng/mL for
Ffluorocholine was identified as the optimal cut-off value in predicting a positive PET/CT scan. Our results demonstrated a better
Ffluciclovine PET/CT DR compared to
Ffluorocholine for restaging PCa patients in early BCR, particularly in the detection of locoregional recurrence. The significantly higher
Ffluciclovine DR for low PSA values (PSA < 1 ng/mL) supports its use in this setting of patients.
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