A wide skull osteolytic metastasis in advanced breast cancer

We present a case report of a large and deep osteolytic metastasis radiological documented involving the skull in a woman affected by advanced breast cancer during endocrine therapy

Prognostic significance of germline BRCA mutations in patients with HER2-POSITIVE breast cancer.

Background: HER2-positive breast cancers are rare amongst BRCA mutation carriers. No data exist regarding clinicopathological characteristics and prognosis of this subgroup of patients. Materials and methods: Using a retrospective matched cohort design, we collected data from 700 women who were diagnosed with operable invasive breast cancer from January 2006 to December 2016 and were screened for germline BRCA mutations. Clinicopathological features and survival rates were analyzed by BRCA and HER2 status. Results: One hundred and fifteen HER2-positive/BRCA mutated cases were evaluated in comparison to the three control groups: HER2-positive/BRCA wild type (n = 129), HER2-negative/BRCA mutated (n = 222), HER2-negative/BRCA wild type (n = 234). HER2-positive breast cancers were more likely to have high histologic grade and high proliferation rate than HER2-negative neoplasms, regardless of BRCA mutation status. An interaction between BRCA mutations and HER2-positive status was found to correlate with worse survival after adjusting for prognostic variables (HR = 3.4; 95% CI: 1.3-16.7). Conclusions: Co-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with early or locally advanced breast cancer. This finding may be a proof of concept that a combined pharmacological intervention directed to these targets could be synergistic

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

Retroperitoneal cystoadenocarcinoma: A case report with a literature review

Primary retroperitoneal mucinous cystoadenocarcinoma (PRMC) is an extremely rare clinical entity with about 50 cases described by the literature. Given the rarity of this pathology, the sharing of accurate available informations is important to improve its knowledge. We reported a case of a woman diagnosed with PRMC who received different lines of chemotherapy and radiotherapy and we also performed a review of the literature on the issue

Effectiveness and safety of “real” concurrent stereotactic radiotherapy and immunotherapy in metastatic solid tumors: a systematic review

Background: in the setting of metastatic malignancies, the role of concurrent stereotactic radiosurgery (SRS)/stereotactic radiotherapy (SRT) and immune-checkpoint inhibitors (ICI) is increasing. Few data are available about effectiveness and safety of this strategy. Methods: we used the PRISMA guidelines to perform a systematic review. We selected only articles reporting a “real” concurrent treatment, defined as SRS/SRT performed within 30 days of ICI administration. Results: Despite several limits due to the heterogeneity and retrospective nature of the studies, 1-year local control for brain lesions ranged from 42 to 100% and 1-year regional brain control ranged from 31 to 83%. An interesting rate of local and distant control was reported for concurrent SBRT-ICI on extra-cranial lesions. No relevant signals about toxicity emerged. Conclusions: Based on published evidence, concurrent SRS/SRT and ICI seems to lead intriguing outcomes, without increasing toxicity. Further investigations are warranted to obtain stronger prospective evidence

Primary Retroperitoneal Cystoadenocarcinoma: A Systematic Review

Background/Aims: The aim of this study was to perform a systematic review on primary retroperitoneal cystoadenocarcinoma (PRC), which is an extremely rare disease. Methods: According to PRISMA guidelines, all the literature about PRC from 1977 to 2015 was reviewed. Thirty articles were selected; characteristics of the patients were collected and described; time to recurrence and overall survival (OS) were investigated when available. Results: Thirty seven patients were included of whom 33 were females; the median age at presentation was 43. PRC was more common in postmenopausal women. Surgery was the standard therapy; the role of chemotherapy and/or radiotherapy was uncertain. Thirty percent of the patients relapsed after 58 months from the surgery; the rupture of the cyst occurred in 13% of the cases and it was associated with poor prognosis as well as premenopausal status. At 125 months from the diagnosis, 72% of the patients were alive and the median OS was not reached. Conclusions: The present systematic review about PRC is the first performed until the date of drafting this paper. We described some clinical features of PRC and their possible prognostic value. No conclusive data can be presented due to the small population analyzed and to publication bias

The legal regulation on the carriage of goods

Tématem této diplomové práce je právní úprava přepravy věci. Jedná se o oblast, která zaujímá významnou roli v ekonomickém fungování společnosti. Právní úprava této problematiky je však značně rozvrstvená mezi soukromoprávní předpisy, mezinárodní úmluvy a částečně též předpisy veřejnoprávní. V této práci je věnována pozornost především prvním dvěma kategoriím. Práce je kromě úvodu a závěru rozčleněna do pěti kapitol, které se pak dále, s výjimkou kapitoly první, dělí na další podkapitoly. Po historickém úvodu, zaměřeném zejména na římské právo, následují postupně tři kapitoly věnované jednotlivým smluvním typům, které mohou být právním důvodem přepravy věci. Jedná se o smlouvu o přepravě věci, smlouvu zasílatelskou a smlouvu o provozu dopravního prostředku. Tyto smlouvy jsou postupně charakterizovány, jsou popsány jejich náležitosti, práva a povinnosti smluvních stran a otázky náhrady škody. V rámci výkladu je upozorňováno na interpretační problémy, které se s úpravou těchto smluv pojí. Průběžně je též poukazováno na to, jak se od sebe tyto jednotlivé smluvní typy odlišují. Srovnávána je též úprava v OZ s úpravou v dnes již neúčinném obchodním zákoníku. Práce se též věnuje problematice přepravních dokladů vztahujících se k přepravě věci. V rámci výkladu je rovněž nastíněno, jak jsou upraveny...The present thesis deals with the legal regulation on the carriage of goods. This issue occupies an important role in everyday economic reality. Legal regulation in this field is highly stratified among legal regulations concerning private law, international agreements and partly among legal regulations concerning public law. This thesis mainly covers the regulation contained in the Czech Civil Code and in international conventions. In addition to the introduction and conclusion, this thesis is divided into five chapters, which are further divided, with the exception of the first chapter, into subchapters. The first chapter, which focuses on historical development and mainly on Roman law, is followed by chapters dealing with particular types of contracts which can be the legal cause for the carriage of goods. These include the following: contract for the carriage of goods, forwarding contract and contract for the operation of a means of transport. Firstly, these contracts are characterized and then the elements of such contracts are described, as well as the duties and rights of the contracting parties and questions regarding compensation for damage. The thesis also points out the interpretative problems that occur in the regulation of these contracts. The differences between these types of...Katedra občanského právaDepartment of Civil LawFaculty of LawPrávnická fakult

Role of innate and adaptive immunity in the efficacy of anti-HER2 monoclonal antibodies for HER2-positive breast cancer

Anti-HER2 monoclonal antibodies (mAbs) such as trastuzumab are effective for all stages of HER2-positive breast cancer (BC). However, intrinsic or acquired resistance to these drugs may occur in a significant number of patients (pts) and, except for HER2 status, no validated predictive factors of response/resistance have been identified to date. This lack is in part due to the not yet fully elucidated mechanism of action of mAbs in vivo. Increasing evidence suggests a significant contribution of both innate and adaptive immunity to the antitumor effects of mAbs. The aim of this review was to describe the role of innate and adaptive immunity in the efficacy of anti-HER2 mAbs and to report known and novel strategies to be used for optimizing immune effects of anti-HER2 therapies for HER2-positive BC