Performance of HPV DNA testing in the follow-up after treatment of high-grade cervical lesions, adenocarcinoma in situ (AIS) and microinvasive carcinoma

BACKGROUND: Over the last two decades it has become clear that distinct types of human papillomavirus (HPV), the so-called high-risk types (hrHPV), are the major cause of cervical cancer. The hrHPV-DNA testing has shown excellent performance in several clinical applications from screening to the follow-up of conservatively treated patients. METHODS: We conducted a systematic review of the recent literature on the performance of HPV DNA testing in follow-up after treatment of high-grade cervical lesions, adenocarcinoma in situ, and microinvasive carcinoma compared to Pap smear cytology. RESULTS: Observational studies have demonstrated that the high risk hrHPV-DNA test is significantly more sensitive (95%) compared to follow-up cytology(70%) in detecting post-treatment squamous intraepithelial high-grade lesions. Moreover, in patients treated conservatively for cervical adenocarcinoma in situ, the hrHPV-DNA test is the most significant independent predictor of recurrent disease or progression to invasive cancer, and the combination of viral DNA testing and cytology reaches 90% sensitivity in detecting persistent lesions at the first follow-up visit and 100% at the second follow-up visit. The cause of microinvasive squamous cervical carcinoma is increasingly treated with conservative therapies in order to preserve fertility, and an effective strategy allowing early detection of residual or progressive disease has become more and more important in post-treatment follow-up. Primary results seem to indicate that the median time for viral clearance is relatively longer compared with patients treated for CIN and suggest a prolonged surveillance for these patients. However, the potential clinical value of HPV-DNA testing in this clinical setting needs to be confirmed by further observations. CONCLUSIONS: The excellent sensitivity, negative predictive value, and optimal reproducibility of the hrHPV DNA testing, currently is considered a powerful tool in the clinicians’ hands to better manage post-treatment follow-up either in cervical squamous lesion or in situ adenocarcinoma

Asymptotic dynamics of short-waves in nonlinear dispersive models

The multiple-scale perturbation theory, well known for long-waves, is extended to the study of the far-field behaviour of short-waves, commonly called ripples. It is proved that the Benjamin-Bona-Mahony- Peregrine equation can propagates short-waves. This result contradict the Benjamin hypothesis that short-waves tends not to propagate in this model and close a part of the old controversy between Korteweg-de Vries and Benjamin-Bona-Mahony-Peregrine equations. We shown that a nonlinear (quadratic) Klein-Gordon type equation substitutes in a short-wave analysis the ubiquitous Korteweg-de Vries equation of long-wave approach. Moreover the kink solutions of phi-4 and sine-Gordon equations are understood as an all orders asymptotic behaviour of short-waves. It is proved that the antikink solution of phi-4 model which was never obtained perturbatively can be obtained by perturbation expansion in the wave-number k in the short-wave limit.Comment: to appears in Physical Review E. 4 pages, revtex file

Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines

Cardiovascular (CV) toxicity is a potential short- or long-term complication of various anticancer therapies. Some drugs, such as anthracyclines or other biological agents, have been implicated in causing potentially irreversible clinically important cardiac dysfunction. Although targeted therapies are considered less toxic and better tolerated by patients compared with classic chemotherapy agents, rare but serious complications have been described, and longer follow-up is needed to determine the exact profile and outcomes of related cardiac side-effects. Some of these side-effects are irreversible, leading to progressive CV disease, and some others induce reversible dysfunction with no long-term cardiac damage to the patient. Assessment of the prevalence, type and severity of cardiac toxicity caused by various cancer treatments is a breakthrough topic for patient management. Guidelines for preventing, monitoring and treating cardiac side-effects are a major medical need. Efforts are needed to promote strategies for cardiac risk prevention, detection and management, avoiding unintended consequences that can impede development, regulatory approval and patient access to novel therapy. These new ESMO Clinical Practice Guidelines are the result of a multidisciplinary cardio-oncology review of current evidence with the ultimate goal of providing strict criteria-based recommendations on CV risk prevention, assessment, monitoring and management during anticancer treatmen

Trends in clinical and oncological outcomes of robot-assisted radical prostatectomy before and after the 2012 US Preventive Services Task Force recommendation against PSA screening: a decade of experience

Objective: To assess the influence of the 2012 US Preventive Services Task Force (USPSTF) recommendation against prostate-specific antigen (PSA)-based screening on oncological and functional outcomes following robot-assisted laparoscopic prostatectomy (RALP). Materials and Methods: We retrospectively analysed patients who underwent RALP between 2008 and 2018 with a minimum of 12-month follow-up from a prospectively collected institutional review board-approved database. The impact of the USPSTF recommendation against PSA screening on our surgical outcomes was assessed using a logistic regression model using two groups comprising patients treated before/after the USPSTF statement and indicating time trends for each successive year. Results: The mean preoperative PSA increased from 6.0 to 7.4 ng/mL after the USPSTF recommendation. We detected statistically significant time-trend changes after 2012, including an increase in the positive slope of Gleason ≥3 + 4 or ≥pT3 disease. We detected a fall in bilateral full nerve-sparing and an increase in partial nerve-sparing. The total positive surgical margin (PSM) rate increased after the USPSTF recommendation; however, PSM rates pertinent to each pathological stage did not change significantly after 2012. There was a significant negative trend change in the postoperative 12-month continence and potency rates, indicating a breakpoint in functional outcomes after 2012. We detected a 1.7-fold increase in 12-month biochemical recurrence (BCR) rates. The 12-month BCR, potency and continence rates were maintained in young (<55 years) patients with a Sexual Health Inventory for Men score >22 and low-volume disease. Conclusion: Since the USPSTF’s recommendation in 2012, we have seen a significant increase in the incidence of high-risk disease that has forced us to modify our approach to the procedure and the grade of nerve-sparing used, leading to a wider resection, in order to reduce PSMs. This has led to a decrease in postoperative functional recovery. Patients with favourable characteristics had good outcomes before and after the USPSTF’s recommendation, implying that the quality of surgery did not change over time

Preliminary study of kaonic deuterium X-rays by the SIDDHARTA experiment at DAFNE

The study of the KbarN system at very low energies plays a key role for the understanding of the strong interaction between hadrons in the strangeness sector. At the DAFNE electron-positron collider of Laboratori Nazionali di Frascati we studied kaonic atoms with Z=1 and Z=2, taking advantage of the low-energy charged kaons from Phi-mesons decaying nearly at rest. The SIDDHARTA experiment used X-ray spectroscopy of the kaonic atoms to determine the transition yields and the strong interaction induced shift and width of the lowest experimentally accessible level (1s for H and D and 2p for He). Shift and width are connected to the real and imaginary part of the scattering length. To disentangle the isospin dependent scattering lengths of the antikaon-nucleon interaction, measurements of Kp and of Kd are needed. We report here on an exploratory deuterium measurement, from which a limit for the yield of the K-series transitions was derived: Y(K_tot)<0.0143 and Y(K_alpha)<0.0039 (CL 90%). Also, the upcoming SIDDHARTA-2 kaonic deuterium experiment is introduced.Comment: Accepted by Nuclear Physics

Strong interaction studies with kaonic atoms

The strong interaction of antikaons (K-) with nucleons and nuclei in the low energy regime represents an active research field connected intrinsically with few-body physics. There are important open questions like the question of antikaon nuclear bound states - the prototype system being K-pp. A unique and rather direct experimental access to the antikaon-nucleon scattering lengths is provided by precision X-ray spectroscopy of transitions in low-lying states of light kaonic atoms like kaonic hydrogen isotopes. In the SIDDHARTA experiment at the electron-positron collider DA?NE of LNF-INFN we measured the most precise values of the strong interaction observables, i.e. the strong interaction on the 1s ground state of the electromagnetically bound K-p atom leading to a hadronic shift and a hadronic broadening of the 1s state. The SIDDHARTA result triggered new theoretical work which achieved major progress in the understanding of the low-energy strong interaction with strangeness. Antikaon-nucleon scattering lengths have been calculated constrained by the SIDDHARTA data on kaonic hydrogen. For the extraction of the isospin-dependent scattering lengths a measurement of the hadronic shift and width of kaonic deuterium is necessary. Therefore, new X-ray studies with the focus on kaonic deuterium are in preparation (SIDDHARTA2). Many improvements in the experimental setup will allow to measure kaonic deuterium which is challenging due to the anticipated low X-ray yield. Especially important are the data on the X-ray yields of kaonic deuterium extracted from a exploratory experiment within SIDDHARTA.Comment: Proc. Few Body 21, 4 pages, 2 figure

Extracellular matrix features discriminate aggressive HER2-positive breast cancer patients who benefit from trastuzumab treatment

We previously identified an extracellular matrix (ECM) gene expression pattern in breast cancer (BC), called ECM3, characterized by a high expression of genes encoding structural ECM proteins. Since ECM is reportedly implicated in response to therapy of BCs, the aim of this work is to investigate the prognostic and predictive value of ECM3 molecular classification in HER2-positive BCs. ECM3 resulted in a robust cluster that identified a subset of 25-37% of HER2-positive tumors with molecular aggressive features. ECM3 was significantly associated with worse prognosis in two datasets of HER2-positive BCs untreated with adjuvant therapy. Analyses carried out on two of our cohorts of patients treated or not with adjuvant trastuzumab showed association of ECM3 with worse prognosis only in patients not treated with trastuzumab. Moreover, investigating a dataset that includes gene profile data of tumors treated with neoadjuvant trastuzumab plus chemotherapy or chemotherapy alone, ECM3 was associated with increased pathological complete response if treated with trastuzumab. In the in vivo experiments, increased diffusion and trastuzumab activity were found in tumors derived from injection of HER2-positive cells with Matrigel that creates an ECM-rich tumor environment. Taken together, these results indicate that HER2-positive BCs classified as ECM3 have an aggressive phenotype but they are sensitive to trastuzumab treatment

X-ray transition yields of low-Z kaonic atoms produced in Kapton

The X-ray transition yields of kaonic atoms produced in Kapton polyimide (C22H10N2O5) were measured for the first time in the SIDDHARTA experiment. X-ray yields of the kaonic atoms with low atomic numbers (Z = 6, 7, and 8) and transitions with high principal quantum numbers (n = 5-8) were determined. The relative yield ratios of the successive transitions and those of carbon-to-nitrogen (C:N) and carbon-to-oxygen (C:O) were also determined. These X-ray yields provide important information for understanding the capture ratios and cascade mechanisms of kaonic atoms produced in a compound material, such as Kapton.Comment: Accepted in Nucl. Phys. A (2013