162 research outputs found
West Nile virus: the Italian national transplant network reaction to an alert in the north-eastern region, Italy 2011
We report four cases of West Nile virus (WNV) transmission following a single multiorgan donation in north-eastern Italy. The transmissions were promptly detected by local transplant centres. The donor had been tested for WNV by nucleic acid amplification test (NAT) prior to transplantation and was negative. There were no detected errors in the nationally implemented WNV safety protocols
Mesonephric-Like Adenocarcinomas a Rare Tumor: The Importance of Diagnosis
Mesonephric-like adenocarcinomas (MLA) are rare neoplasms that arise in the uterine body and ovary and have been added to the World Health Organisationâs recent 2020 classification of female genital cancers. The pathogenesis of MLA is unknown and it remains debated whether they represent mesonephric carcinomas (Wolffian) arising in the endometrium/ovary or endometrioid carcinomas (MĂŒllerian) closely mimicking mesonephric carcinomas. Here we report the case of a 57-year-old woman with an initial misdiagnosis of endometrioid adenocarcinoma on diagnostic biopsy. The patient came to our clinical evaluation for the appearance of menometrorrhagia complicated by anemia for several months. Therefore, she underwent pelvic echo-flowmetry, with indication for diagnostic hysteroscopy with endometrial biopsy, which yielded a positive result for endometrioid endometrial adenocarcinoma. Following staging CT scan and targeted examinations on pulmonary findings, the patient underwent surgery with surprise of definitive diagnosis deponent for endometrial MLA. Our intention is to establish a brief review of the scientific evidence in the literature and the tools available for a correct histological diagnosis, in the light of the scant anatomopathological evidence. Our question gives rise to the motive for the publication: is immunohistochemistry the right way to resolve the diagnostic error at histology, which is usually the only source of diagnostic certainty? This case is intended to alert of diagnostic error that risked having the patient treated as a neoplasm with a favorable prognosis and low degree of aggressiveness instead of for a very aggressive and poor prognosis tumor such as MLA
CUP-syndrome: Inguinal high grade serous ovarian carcinoma lymph node metastases with unknown primary origin â a case report and literature review
Objective: High-grade serous ovarian carcinoma (HGSC) often presents lymph node involvement. According to the paths of lymphatic drainage, the most common site of nodal metastasis is in the aortic area. However, pelvic lymph nodes are also involved and inguinal metastases are less frequent. Methods: Our report concerns the case of a 78-year-old woman with an inguinal lymph node relapse of HGSC, with the prior positivity of a right inguinal lymph node, after the primary surgery. Ovaries and tubes were negative on histological examination. A comprehensive search of the literature published from January 2000 to October 2021 was conducted on PubMed and Scopus. The papers were selected following the PRISMA guidelines. Nine retrospective studies were evaluated. Results: Overall, 67 studies were included in the initial search. Applying the screening criteria, 36 articles were considered eligible for full-text reading of which, after applying the exclusion criteria, 9 studies were selected for the final analysis and included in the systematic review. No studies were included for a quantitative analysis. We divided the results according to the relapse location: loco-regional, abdominal, and extra-abdominal recurrence. Conclusions: Inguinal node metastasis is a rare but not unusual occurrence in HGSC. A reasonable level of suspicion should be maintained in patients with inguinal adenopathy and high CA125 values, especially in women with a history of gynecologic surgery, even in the absence of negative imaging for an ovarian origin
HIPEC after Interval Debulking Surgery as Best Clinical Practice in Ovarian Cancer Patients: Case Series and Literature Review
Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with interval debulking surgery (IDS) constitutes an adjunctive treatment strategy in advanced ovarian cancer (AOC). This approach is based on the concept of perfusing chemotherapy targeting directly the site of residual tumor after optimal surgical debulking. It improves patients' outcome in terms of overall survival (OS) and disease free survival (DFS). The correct selection of patients eligible for IDS + HIPEC is crucial: in particular, they must have shown a good response to neoadjuvant chemotherapy (NACT) and have a good performance status (PS). The application of HIPEC at the end of debulking does not seem to increase neither the rate of intra/postoperative complications nor the time of hospitalization. Clinical Cases: After approving an internal protocol for the application of HIPEC in our hospital, we have submitted four patients to IDS + HIPEC in the past 12 months. One of these patients underwent a minimally invasive procedure. No intra- or postoperative complications were observed. Results: All patients underwent IDS + HIPEC after being assessed as eligible and after showing a good response to NACT. In the course of IDS in all cases complete debulking was achieved. No patient developed intra- or postoperative complications. Conclusions: The addition of HIPEC to interval debulking surgery should be offered to all eligible patients, considering that the association of HIPEC to IDS seems to improve patients' outcomes in terms of OS and DFS, without increasing post-operative morbidity
Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized
Understanding protein structure is of crucial importance in science, medicine
and biotechnology. For about two decades, knowledge based potentials based on
pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been
center stage in the prediction and design of protein structure and the
simulation of protein folding. However, the validity, scope and limitations of
these potentials are still vigorously debated and disputed, and the optimal
choice of the reference state -- a necessary component of these potentials --
is an unsolved problem. PMFs are loosely justified by analogy to the reversible
work theorem in statistical physics, or by a statistical argument based on a
likelihood function. Both justifications are insightful but leave many
questions unanswered. Here, we show for the first time that PMFs can be seen as
approximations to quantities that do have a rigorous probabilistic
justification: they naturally arise when probability distributions over
different features of proteins need to be combined. We call these quantities
reference ratio distributions deriving from the application of the reference
ratio method. This new view is not only of theoretical relevance, but leads to
many insights that are of direct practical use: the reference state is uniquely
defined and does not require external physical insights; the approach can be
generalized beyond pairwise distances to arbitrary features of protein
structure; and it becomes clear for which purposes the use of these quantities
is justified. We illustrate these insights with two applications, involving the
radius of gyration and hydrogen bonding. In the latter case, we also show how
the reference ratio method can be iteratively applied to sculpt an energy
funnel. Our results considerably increase the understanding and scope of energy
functions derived from known biomolecular structures
Ki67 as a Predictor of Response to PARP Inhibitors in Platinum Sensitive BRCA Wild Type Ovarian Cancer: The MITO 37 Retrospective Study.
There is compelling need for novel biomarkers to predict response to PARP inhibitors (PARPi) in BRCA wild-type (WT) ovarian cancer (OC).
MITO 37 is a multicenter retrospective study aiming at correlating Ki67 expression at diagnosis with a clinical outcome following platinum treatment and PARPi maintenance. Clinical data were collected from high grade serous or endometroid BRCAWT OC treated with niraparib or rucaparib maintenance between 2010-2021 in 15 centers. Ki67 expression was assessed locally by certified pathologists on formalin-fixed paraffin embedded (FFPE) tissues. Median Ki67 was used as a cut-off.
A total of 136 patients were eligible and included in the analysis. Median Ki67 was 45.7% (range 1.0-99.9). The best response to platinum according to median Ki67 was 26.5% vs. 39.7% complete response (CR), 69.1% vs. 58.8% partial response (PR), 4.4% vs. 1.5% stable disease (SD). The best response to PARPi according to median Ki67 was 19.1% vs. 36.8% CR, 26.5% vs. 26.5% PR, 26.5 vs. 25% SD, 27.9% vs. 16.2% progressive disease (PD). No statistically significant differences in progression free survival (PFS) and overall survival (OS) were identified between low and high Ki67. PFS and OS are in line with registration trials.
Ki67 at diagnosis did not discriminate responders to PARPi
Everolimus plus aromatase inhibitors as maintenance therapy after first-line chemotherapy: Final results of the phase III randomised MAIN-A (MAINtenance Afinitor) trial
Background: Despite endocrine therapy being the mainstay of treatment for hormone receptor positive (HR+)/HER2 12 metastatic breast cancer, patients at risk of visceral crisis or doubt for endocrine sensitivity are still offered first-line chemotherapy. Maintenance hormonal therapy is generally offered at the discontinuation of chemotherapy. The MAINtenance Afinitor study is a randomised, phase III trial comparing maintenance everolimus combined with aromatase inhibitors (AIs) versus AI monotherapy in patients with disease control after first-line chemotherapy. Methods: Patients with stable disease, partial response or complete response after first-line chemotherapy were randomised to everolimus plus AIs (exemestane or letrozole or anastrozole) or to AIs alone. Primary aim was progression-free survival (PFS). Secondary aims included response rate, safety and overall survival (OS). Results: In total, 110 patients were randomised to everolimus + AIs (n = 52) or to AIs (n = 58). Median PFS was 11.0 months (95% confidence interval [CI] 8.1\u201313.8) in the everolimus + AI arm and 7.2 months (95% CI 4.7\u201310.9) in the AI monotherapy arm (hazard ratio [HR] 0.71, 95% CI 0.47\u20131.06). Objective response rate was 22.4% in everolimus + AI arm and 19.2% in AI monotherapy arm. A higher proportion of disease progression as best response was reported in the AI monotherapy arm (28.8% versus 14.3%). Median OS was 35.7 months (95% CI 26.0\u201347.8) in the combination arm versus 33.5 (95% CI 26.4\u201342.7) in the AI alone arm (HR 1.0, 95% CI 0.61\u20131.62). Conclusions: EVE + AIs did not significantly impact on the outcome of metastatic breast cancer patients deemed suitable for first-line chemotherapy. Also taking into account treatment tolerability, maintenance endocrine therapy remains the standard. Trial registration: EudraCT: 2013-004153-24
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