A prospective study on the early evaluation of response to androgen receptor-targeted agents with 11C-Choline, 68Ga-PSMA, and 18F-FACBC PET in metastatic castration-resistant prostate cancer: a single-center experience.

BACKGROUND: The early identification of responsive and resistant patients to androgen receptor-targeting agents (ARTA) in metastatic castration-resistant prostate cancer (mCRPC) is not completely possible with prostate-specific antigen (PSA) assessment and conventional imaging. Considering its ability to determine metabolic activity of lesions, positron emission tomography (PET) assessment might be a promising tool. PATIENTS AND METHODS: We carried out a monocentric prospective study in patients with mCRPC treated with ARTA to evaluate the role of different PET radiotracers: 49 patients were randomized to receive 11C-Choline, Fluorine 18 fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid - FACBC) (18F-FACBC), or Gallium-68-prostate-specific-membrane-antigen (68Ga-PSMA) PET, one scan before therapy and one 2 months later. The primary aim was to investigate the performance of three novel PET radiotracers for the early evaluation of response to ARTA in metastatic CRPC patients; the outcome evaluated was biochemical response (PSA reduction ≥50%). The secondary aim was to investigate the prognostic role of several semiquantitative PET parameters and their variations with the different radiotracers in terms of biochemical progression-free survival (bPFS) and overall survival (OS). The study was promoted by the Italian Department of Health (code RF-2016-02364809). RESULTS: Regarding the primary endpoint, at log-rank test a statistically significant correlation was found between metabolic tumor volume (MTV) (P = 0.018) and total lesion activity (TLA) (P = 0.025) percentage variation among the two scans with 68Ga-PSMA PET and biochemical response. As for the secondary endpoints, significant correlations with bPFS were found for 68Ga-PSMA total MTV and TLA at the first scan (P = 0.001 and P = 0.025, respectively), and MTV percentage variation (P = 0.031). For OS, statistically significant correlations were found for different 68Ga-PSMA and 18F-FACBC parameters and for major maximum standardized uptake value at the first 11C-Choline PET scan. CONCLUSIONS: Our study highlighted that 11C-Choline, 68Ga-PSMA, and 18F-FACBC semiquantitative PET parameters and their variations present a prognostic value in terms of OS and bPFS, and MTV and TLA variations with 68Ga-PSMA PET a correlation with biochemical response, which could help to assess the response to ARTA.

The molecular profiling of solid tumors by liquid biopsy: a position paper of the AIOM-SIAPEC-IAP-SIBioC-SIC-SIF Italian Scientific Societies.

The term liquid biopsy (LB) refers to the use of various biological fluids as a surrogate for neoplastic tissue to achieve information for diagnostic, prognostic and predictive purposes. In the current clinical practice, LB is used for the identification of driver mutations in circulating tumor DNA derived from both tumor tissue and circulating neoplastic cells. As suggested by a growing body of evidence, however, there are several clinical settings where biological samples other than tissue could be used in the routine practice to identify potentially predictive biomarkers of either response or resistance to targeted treatments. New applications are emerging as useful clinical tools, and other blood derivatives, such as circulating tumor cells, circulating tumor RNA, microRNAs, platelets, extracellular vesicles, as well as other biofluids such as urine and cerebrospinal fluid, may be adopted in the near future. Despite the evident advantages compared with tissue biopsy, LB still presents some limitations due to both biological and technological issues. In this context, the absence of harmonized procedures corresponds to an unmet clinical need, ultimately affecting the rapid implementation of LB in clinical practice. In this position paper, based on experts' opinions, the AIOM-SIAPEC-IAP-SIBIOC-SIF Italian Scientific Societies critically discuss the most relevant technical issues of LB, the current and emerging evidences, with the aim to optimizing the applications of LB in the clinical setting.

The understanding of congruent and incongruent referential gaze in 17-month-old infants: an eye-tracking study comparing human and robot.

Several studies have shown that the human gaze, but not the robot gaze, has significant effects on infant social cognition and facilitate social engagement. The present study investigates early understanding of the referential nature of gaze by comparing-through the eye-tracking technique-infants' response to human and robot's gaze. Data were acquired on thirty-two 17-month-old infants, watching four video clips, where either a human or a humanoid robot performed an action on a target. The agent's gaze was either turned to the target (congruent) or opposite to it (incongruent). The results generally showed that, independent of the agent, the infants attended longer at the face area compared to the hand and target. Additionally, the effect of referential gaze on infants' attention to the target was greater when infants watched the human compared to the robot's action. These results suggest the presence, in infants, of two distinct levels of gaze-following mechanisms: one recognizing the other as a potential interactive partner, the second recognizing partner's agency. In this study, infants recognized the robot as a potential interactive partner, whereas ascribed agency more readily to the human, thus suggesting that the process of generalizability of gazing behaviour to non-humans is not immediate.

Case report of a successful multidisciplinary approach to a giant scrotal malformation.

INTRODUCTION: Congenital pelvic malformations are rare and represent a difficult therapeutic challenge. Scrotal arteriovenous malformations are quite unusual, with only a few such cases reported in the literature. Only one case of scrotal malformation? due to an arteriovenous fistula resulting in azoospermia has been described. PRESENTATION OF CASE: The two-phase strategy adopted in that case permitted complete treatment of a large-sized malformation that was served by 4 main blood confluences. DISCUSSION: Angio-CT performed using reconstructions with MIP and SSD algorithms provided more detailed data about the extension of the afferents and efferents of the arteriovenous malformation, thus enabling us to plan the endovascular treatment of the lesion. CONCLUSION: A multidisciplinary approach is mandatory to achieve good results in these cases.

Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer.

BACKGROUND: Ipsilateral breast cancer recurrence (IBTR) occurs in about 7% of patients with primary invasive breast tumor. Salvage mastectomy and breast reconstruction are often discussed and latissimus dorsi (LD) flap is frequently proposed. METHODS: We retrospectively investigated 111 consecutive locally relapsing patients who underwent salvage mastectomy and immediate LD reconstruction. All included patients with IBTR previously underwent conserving surgery for BC, and received a postoperative irradiation. Primary endpoints were disease free survival and overall survival. Secondary endpoints were surgical complications and re-interventions. RESULTS: Invasive ductal cancer was the most frequent histotype (60.4%) of breast cancer reappearance. rpT1, rpT2 and rpT3 were observed respectively in 50.5%, 20,7% and 3,6% of the patients. rpTis occurred in 11,7% of cases. Positive axillary nodes were observed in 9,9% of patients at reappearance. Post-operative complication other than seroma occurred in 17,1% of patients, while seroma at the donor site was observed in 61.3% of cases. At 5-year after surgery overall survival was 92% (95% CI: 85%-96%) and disease free survival was 78% (95% CI: 69%-85%). CONCLUSIONS: Immediate latissimus dorsi flap reconstruction in selected patients with isolated breast tumor recurrence, which occurred after breast irradiation, provides an effective treatment with a satisfactory outcome.

Predictive markers in lung cancer: a few hints for the practicing pathologist.

This review article highlights some important points in the evolving area of predictive biomarkers determination in non-small-cell lung cancer toward standardization of testing practices, including EGFR mutations, ALK and ROS1 rearrangements and immunohistochemical expression of PD-L1. Considerations for selecting appropriate populations for molecular testing, and emergence of other targetable molecular alterations are also discussed.

Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: results from the ETOP Lungscape Project.

Background: Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods: Clinically annotated, resected stage I-III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is >1% for most of the ∼150 (13 genes) mutations covered in the multiplex test. Results: Multiplex testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8 years). FFPE samples mostly date from 2005 to 2008, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63 µg; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of included cases allowed the complete panel of mutations to be tested. Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups. EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers. For all the above mutations, there was no difference in outcome between mutated and non-mutated cases. Conclusion: Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically annotated stage I-III NSCLC cohort, none of the mutations characterized showed prognostic significance.

EVAR and OPEN treatment of abdominal aortic aneurysm: What is the role of MMP-9 in the follow-up?

INTRODUCTION: The aim of our study is to verify the role of metalloproteinases in endovascular repair (EVAR) and OPEN surgery treatment for abdominal aortic aneurysm (AAA). Postoperatively, these enzymes could represent an important biomarker to adapt diagnostic tests and further investigations during follow-up. MATERIAL AND METHOD: From 2004 to 2008, 55 patients were considered with AAA. Of these, 33 patients (mean age: 70.1 years), (mean AAA diameter: 5.4cm) were treated with OPEN surgery (group A) and 22 (mean age: 74.1 years) (mean AAA diameter: 5.1cm) were treated with EVAR. In 17 of them, there were no signs of endoleak (group B1), while in 5 patients, a presence of endoleak (group B2) was detected. Plasma samples were collected in order to determine MMP-9 activity. Enzyme immunoassay was performed preoperatively at 1, 3, 6 and 12 months. Patients treated conventionally were clinically examined after 1 and 12 months by ultrasound. Patients undergoing EVAR treatment were clinically examined by CT scan after 1, 3, 6 and 12 months. The analysis was done by assessing the interaction over time of the MMP-9 value in B1 and B2 groups. RESULTS: The average values observed for MMP-9 were preoperatively and at 1, 3, 6 and 12 months, respectively: in group A 150.8ng/mL (SD=30.5), 252.5ng/mL (SD=25.2), 315.4ng/mL (SD=22.7), 295.3ng/mL (SD=26.8), 210.7ng/mL (SD=30.2); in group B1 105ng/mL (SD=10.8), 125.6ng/mL (SD=18), 85.8ng/mL (SD=19.9), 95ng/mL (SD=20.2), 80.4ng/mL (SD=15.6); in group B2 149ng/mL (29.2), 375.4ng/mL (SD=40.2), 215ng/mL (SD=35.9), 180ng/mL (SD=20.2), 175ng/mL (SD=33.4). The MMP-9 level was higher in group B2 compared to group B1 (P=0.01), suggesting a correlation with the presence of the endoleak. CONCLUSIONS: This preliminary study shows that MMP-9 may be a biomarker of the presence of endoleak. Other further investigations and larger series are needed to show that metalloproteases could play a role in the follow-up of EVAR treated patients.

Inflammatory and Adipose Response in Solid Organ Transplant Recipients After a Marathon Cycling Race.

BACKGROUND: Organ transplant recipients frequently have chronic inflammation, with a weighty impact on cardiovascular risk. These patients can benefit from exercise, although the role of intense training is unclear. We evaluated the effect of a 130-km cycling race on inflammatory cytokines and adiponectin levels in transplant recipients. METHODS: Circulating interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and adiponectin were assayed in 35 healthy subjects vs 19 transplant recipients (10 kidney, 8 liver, 1 heart), matched for sex, age, body mass index, and preparation workout. The determinations were performed before the race, at the end, and after 18 to 24 hours. Baseline values of 32 sedentary transplant recipients also were evaluated to explore the possible chronic impact of lifestyle. RESULTS: All cyclists had 6- to 8-fold increased IL-6 levels after the race that decreased, without returning to baseline, the day after. Conversely, serum TNF-α and IFN-γ showed a progressive increase starting during physical performance and enduring for the next 18 to 24 hours in healthy subjects, whereas they were unchanged over time in cyclists with transplants. In transplant recipients who did not perform exercise, all of the analytes were significantly higher in comparison to basal levels of physically active subjects. CONCLUSIONS: Our data suggest that clinically stable and properly trained transplant recipients can safely perform and progressively benefit from exercise, even at a competitive level. The changes in inflammation parameters were temporary and parallel with those of the healthy subjects. The comparison with sedentary transplant recipients revealed an overall amelioration of inflammatory indexes as a possible effect of regular physical activity on systemic inflammation.

Tracing mercury pathways in Augusta Bay (southern Italy) by total concentration and isotope determination.

The mercury (Hg) pollution of sediments is the main carrier of Hg for the biota and, subsequently, for the local fish consumers in Augusta Bay area (SE Sicily, Italy), a coastal marine system affected by relevant sewage from an important chlor-alkali factory. This relationship was revealed by the determination of Mass Dependent (MDF) and Mass Independent Fractionation (MIF) of Hg isotopes in sediment, fish and human hair samples. Sediments showed MDF but no MIF, while fish showed MIF, possibly due to photochemical reduction in the water column and depending on the feeding habitat of the species. Benthic and demersal fish exhibited MDF similar to that of sediments in which anthropogenic Hg was deposited, while pelagic organisms evidenced higher MDF and MIF due to photoreduction. Human hair showed high values of δ(202)Hg (offset of +2.2‰ with respect to the consumed fish) and Δ(199)Hg, both associated to fish consumption.

Stakeholders in nursing education: their role and involvement.

INTRODUCTION: In literature, there is evidence that all stakeholders need to be involved in the curricula building process to make sure that health professionals are "educated" to meet the stakeholders' "demands". In Italy, the involvement of stakeholders in the definition of university curricula is ratified by various regulations. AIMS: To describe the major experiences of stakeholder involvement in nursing education, identify the main stakeholders for nursing education, and the processes in which they are involved. METHODS: The search strategy included an electronic exploration of the relevant databases. The search terms were: Stakeholders, Curriculum, Nursing Education combined with Boolean operators. The references of the retrieved articles were hand searched for additional related studies. RESULTS: Most of the studies identified were from the United Kingdom, Australia, and the USA. In Italy, no relevant studies were found. The most frequently identified stakeholders were: students, clinicians, educators, nurse managers. They were mainly involved during profound changes in the curricula and the implementation of new educational approaches. DISCUSSION AND CONCLUSIONS: Stakeholders are mostly involved in countries with a private funding system for universities. Such funding systems have probably developed in the academia a greater propensity to involve stakeholders, to provide recognition of success when starting new programs, and are perceived more as marketing research. This seems contrary to the spirit of the Italian and European regulatory interventions, which instead, provide a structured commitment to consolidating and expanding the collaboration among universities, users, and the world of labor. This latter collaboration should facilitate internship activities, lifelong learning, and employability of the newly-graduated professionals.