Heterogeneous response to target therapy in metastatic papillary renal cell carcinoma evaluated by morphologic and metabolic multimodality imaging

Papillary renal cell carcinoma (PRCC) accounts for about 15% to 20% of renal cell carcinoma and is histologically distinguished in type I and type II. The last one is associated with poorer prognosis. Treatment options for PRCC patients are surgery, immunotherapy, revolutionized by Nivolumab, and other target-therapy with an improvement in overall survival. Heterogenous response and a pseudo-progression may be observed in the initial phase of biological treatment that could induce premature discontinuation. Patient concerns: We present the case of a 44-year-old woman with left cervical palpable mass increased in size and without concomitant disease or previous surgery. Diagnosis: Neck ultrasonography, contrast-enhanced Computed Tomography, and 18F-FDG PET/CT were performed with the detection of lymph nodes involvement and a left renal lesion. Interventions: The patients underwent left radical nephrectomy and homolateral cervical and para-aortic lymphadenectomy, with histological diagnosis of PRCC, type II. After disease relapse, the inter-aortocaval lymph node was laparoscopically removed. Following the detection of further disease relapse in several lymph nodes and the lung, several lines of target-therapy were started; then disease progression and worsening of clinical and hematological status led us to start Nivolumab as last-line therapy. Outcomes: A heterogeneous response to therapies was documented with morphological and nuclear medicine imaging, however the concomitant deterioration of performance status and liver function led to discontinuation of Nivolumab; then the patient died, 30 months after diagnosis. Lessons: Here we describe the clinical case and radiological and nuclear medicine imaging investigations performed by our patient, highlighting that 18F-FDG PET/CT shows greater adequacy in assessing the response to therapy, avoiding premature drug discontinuation, and ensuring better management of a patient with advanced PRCC

AXL is an oncotarget in human colorectal cancer

AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell proliferation migration and angiogenesis. We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic inhibition with foretinib suppressed proliferation, migration and survival in CRC cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL, foretinib treatment caused significant inhibition of tumour growth and peritoneal metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC) were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens, correlating with less differentiated histological grading. GAS6 overexpression was associated with nodes involvement and tumour stage. AXL gene was found amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of CRC samples. Taken together, AXL inhibition could represent a novel therapeutic approach in CRC

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe

The day after mass COVID-19 vaccination: incidence of vaccine-related lymphadenopathy PET and impact on oncologic patients management

The widespread COVID-19 vaccination led to unexpected PET findings. Notably, axillary and interpectoral lymphadenopathies ipsilateral to the vaccine inoculation were observed. We aimed to assess the hypermetabolic lymphadenopathy (HLN) detection rate on PET/CT. Secondly, we investigated factors that might help in HLN differential diagnosis. A retrospective analysis on 1196 consecutive patients referred for a PET/CT was performed. All patients were asked about the date, type and site of vaccine injections. HLNs were recorded and categorized according to risk classes and SUVmax grades. A statistical analysis was performed to assess the correlation between HLN detection and different clinical/vaccine data. HLN detection rate was 15% and 27% in the No Vac- and vac-groups (p < 0.001), respectively. In the Vac-group, age (p < 0.001) and time interval from vaccineto- PET (p = 0.010) were inversely correlated with HLN detection. Furthermore, SUVmax significantly changed during time intervals, with lower values beyond 20 days (p < 0.001). In the era of mass COVID-19 vaccination, a higher axillary and interpectoral lymphadenopathies detection ipsilateral to vaccine injection was observed. These PET findings can be wrongly interpreted, complicating cancer patients’ management. To minimize these pitfalls, a detailed vaccination anamnesis must be recorded and should take into account the appropriate PET schedule

The Day after Mass COVID-19 Vaccination: Higher Hypermetabolic Lymphadenopathy Detection on PET/CT and Impact on Oncologic Patients Management

The widespread COVID-19 vaccination led to unexpected PET findings. Notably, axillary and interpectoral lymphadenopathies ipsilateral to the vaccine inoculation were observed. We aimed to assess the hypermetabolic lymphadenopathy (HLN) detection rate on PET/CT. Secondly, we investigated factors that might help in HLN differential diagnosis. A retrospective analysis on 1196 consecutive patients referred for a PET/CT was performed. All patients were asked about the date, type and site of vaccine injections. HLNs were recorded and categorized according to risk classes and SUVmax grades. A statistical analysis was performed to assess the correlation between HLN detection and different clinical/vaccine data. HLN detection rate was 15% and 27% in the No Vac- and vac-groups (p < 0.001), respectively. In the Vac-group, age (p < 0.001) and time interval from vaccine-to-PET (p = 0.010) were inversely correlated with HLN detection. Furthermore, SUVmax significantly changed during time intervals, with lower values beyond 20 days (p < 0.001). In the era of mass COVID-19 vaccination, a higher axillary and interpectoral lymphadenopathies detection ipsilateral to vaccine injection was observed. These PET findings can be wrongly interpreted, complicating cancer patients’ management. To minimize these pitfalls, a detailed vaccination anamnesis must be recorded and should take into account the appropriate PET schedule

Intracranial Solitary Fibrous Tumor: A “New” Challenge for PET Radiopharmaceuticals

Solitary fibrous tumor (SFT) of the central nervous system, previously named and classified with the term hemangiopericytoma (HPC), is rare and accounts for less than 1% of all intracranial tumors. Despite its benign nature, it has a malignant behavior due to the high rate of recurrence and distant metastasis, occurring in up to 50% of cases. Surgical resection of the tumor is the treatment of choice. Radiotherapy represents the gold standard in the case of post-surgery residual disease, relapse, and distant metastases. In this context, imaging plays a crucial role in identifying the personalized therapeutic decision for each patient. Although the referring imaging approach in SFT is morphologic, an emerging role of positron emission tomography (PET) has been reported in the literature. However, there is still a debate on which radiotracers have the best accuracy for studying these uncommon tumors because of the histological or biological heterogeneity of SFT