Nab-paclitaxel in pretreated metastatic breast cancer: evaluation of activity, safety, and quality of life

Objective: Metastatic breast cancer (MBC) is an incurable disease; the treatment of this disease prolongs survival, improving the quality of life (QoL) with a balance between efficacy and toxicity of the treatment. In recent years, treatment with nab-paclitaxel has improved the already known antitumor activity of conventional paclitaxel, in terms of increased efficacy and better tolerability. The aim of this study was to evaluate nab-paclitaxel in Italian patients with MBC. Methods: We conducted a retrospective analysis of 90 patients with histologically confirmed diagnosis of MBC. To evaluate the efficacy of nab-paclitaxel, overall survival (OS), progression-free survival (PFS), and overall response rate were the primary endpoints, whereas carbohydrate antigen 15.3 (Ca15.3) reduction, QoL, and tolerability were secondary endpoints. Results: The median OS was 10.4 months, the median PFS was 6.8 months. A considerable difference Ca15.3 before and after treatment was observed. Descriptive and regression analyses were done to examine the associations between Ca15.3 response and OS, demonstrating good correlation, revealing that Ca15.3 reduction is an important predictor of OS. Conclusion: Nab-paclitaxel is an effective and well-tolerated treatment of patients affected by MBC. The drug showed an improved tolerability profile. With all the limitations of the observational nature of our results, nab-paclitaxel has proven to be an effective and safe therapeutic option in patients with MBC

Il dolore nella sclerosi sistemica. Applicazione di un metodo di valutazione clinica che include l?uso del Mc Gill Pain Questionnaire.

Il dolore nella sclerosi sistemica. Applicazione di un metodo di valutazione clinica che include l’uso del Mc Gill Pain Questionnaire. Scopo della ricerca è esaminare la possibilità di applicazione clinica di diversi metodi di valutazione del dolore in soggetti con sclerosi sistemica, I pazienti esaminati afferivano all'ambulatorio del Centro di Riferimento Regionale Diagnosi e cura per la Sclerodermia SOD Reumatologia Azienda Ospedaliera Universitaria Careggi di Firenze. La presenza di una sintomatologia dolorosa, è stata riferita da 35 pazienti, pari al 79% del campione esaminato, comprendente 44 pazienti. La presenza del dolore non è risultata in relazione né con la durata della malattia, né con l'estensione dell'interessamento cutaneo, né con la presenza di particolari auto anticorpi, né con la presenza di un interessamento viscerale

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer

Purpose: Pancreatic carcinoma is the neoplasia with the major mortality, and main standard treatments in this cancer increase survival but do not lead to complete recovery of the patient. The aim of this study was to evaluate the efficacy of Abraxane® (nab-paclitaxel) in Italian patients with metastatic pancreatic cancer (MPC). Patients and methods: We conducted a retrospective analysis of 80 patients. Overall survival (OS) was the primary end point for evaluating the efficacy of nab-paclitaxel in combination with gemcitabine treatment, while carbohydrate antigen 19-9 (CA 19-9) reduction, safety, progression-free survival (PFS), overall response rate and reduction in pain were secondary end points. Results: The median OS was 8 months, and the median PFS was 5 months. A considerable difference in CA 19-9 before and after treatment was observed. Descriptive and correlation analyses were done to examine the relationship between CA 19-9 response and OS. Linear regression analysis between OS and CA 19-9 response revealed that CA 19-9 is an important predictor of OS, showing a positive correlation. Conclusion: Nab-paclitaxel is a well-tolerated and effective treatment for patients affected by MPC. The drug showed an improved tolerability profile, significant pain relief and an increase in survival rate

Exosome-mediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma

BACKGROUND: Growing evidence is showing that metastatic cell populations are able to transfer their characteristics to less malignant cells. Exosomes (EXOs) are membrane vesicles of endocytic origin able to convey their cargo of mRNAs, microRNAs (miRs), proteins and lipids from donors to proximal as well as distant acceptor cells. Our previous results indicated that miR-221&222 are key factors for melanoma development and dissemination. The aim of this study was to verify whether the tumorigenic properties associated with miR-222 overexpression can be also propagated by miR-222-containing EXOs. METHODS: EXOs were isolated by UltraCentrifugation or Exoquick-TC(®) methods. Preparations of melanoma-derived vesicles were characterized by using the Nanosight™ technology and the expression of exosome markers analyzed by western blot. The expression levels of endogenous and exosomal miRNAs were examined by real time PCR. Confocal microscopy was used to evaluate transfer and uptake of microvesicles from donor to recipient cells. The functional significance of exosomal miR-222 was estimated by analyzing the vessel-like process formation, as well as cell cycle rates, invasive and chemotactic capabilities. RESULTS: Besides microvesicle marker characterization, we evidenced that miR-222 exosomal expression mostly reflected its abundance in the cells of origin, correctly paralleled by repression of its target genes, such as p27Kip1, and induction of the PI3K/AKT pathway, thus confirming its functional implication in cancer. The possible differential significance of PI3K/AKT blockade was assessed by using the BKM120 inhibitor in miR-222-transduced cell lines. In addition, in vitro cultures showed that vesicles released by miR-222-overexpressing cells were able to transfer miR-222-dependent malignancy when taken-up by recipient primary melanomas. Results were confirmed by antagomiR-221&222 treatments and by functional observations after internalization of EXOs devoid of these miRs

Angular deflection of rotary nickel titanium files: a comparative study

A new manufacturing method of twisting nickel titanium wire to produce rotary nickel titanium (RNT) files has recently been developed. The aim of the present study was to evaluate whether the new manufacturing process increased the angular deflection of RNT files, by comparing instruments produced using the new manufacturing method (Twisted Files) versus instruments produced with the traditional grinding process. Testing was performed on a total of 40 instruments of the following commercially available RNT files: Twisted Files (TF), Profile, K3 and M2 (NRT). All instruments tested had the same dimensions (taper 0.06 and tip size 25). Test procedures strictly followed ISO 3630-1. Data were collected and statistically analyzed by means ANOVA test. The results showed that TF demonstrated significantly higher average angular deflection levels (P<0.05), than RNT manufactured by a grinding process. Since angular deflection represent the amount of rotation (and consequently deformation) that a RNT file can withstand before torsional failure, such a significant improvement is a favorable property for the clinical use of the tested RNT files

Effects of physical activity on endothelial progenitor cells (EPCs)

Physical activity has a therapeutic role in cardiovascular disease (CVD), through its beneficial effects on endothelial function and cardiovascular system. Circulating endothelial progenitor cells (EPCs) are bone marrow (BM) derived cells that represent a novel therapeutic target in CVD patients, because of their ability to home to sites of ischemic injury and repair the damaged vessels. Several studies show that physical activity results in a significant increase in circulating EPCs, and, in particular, there are some evidence of the beneficial exercise-induced effects on EPCs activity in CVD settings, including coronary artery disease (CAD), heart failure (HF), and peripheral artery disease (PAD). The aim of this paper is to review the current evidence about the beneficial effects of physical exercise on endothelial function and EPCs levels and activity in both healthy subjects and patients with CVD

Attenuated polyposis of the large bowel: a morphologic and molecular approach

Attenuated polyposis could be defined as a variant of familial adenomatous polyposis (FAP) in which synchronous polyps of the large bowel range between 10 and 99. We analysed all cases of attenuated polyposis observed over the last 30 years with the objectives: (A) to classify the disease according to different type and proportion of polyps; (B) To ascertain the contribution of APC and MutYH genes; (C) to discover features which could arise the suspicion of mutations; (D) To obtain indications for management and follow-up. 84 individuals in 82 families were studied. Polyps were classified into four groups as adenoma, hyperplastic, other serrated lesions or others; APC and MutYH mutations were assessed. Mean age at diagnosis was 54 ± 14 years in men and 48 ± 13 in women (P = 0.005). Polyps were more numerous in women (37 ± 26 vs 29 ± 22). Sixty % of patients underwent bowel resection, mainly for cancer; the remaining were managed through endoscopy. A total of 2586 polyps were detected at diagnostic endoscopy: 2026 (80 %) were removed and analysed. Adenomas were diagnosed in 1445 (70 %), hyperplastic polyps in 541 (26 %), other serrated lesions in 61 (2.9 %). Adenomas and hyperplastic lesions were detected in the majority of patients. In 68 patients (81 %) in whom studies were executed, APC mutations were found in 8 and MutYH mutations in 10. Genetic variants were more frequent in women (12 vs 6, P = 0.039). Taking into consideration the prevalent (&gt;50 %) histology and presence of mutations, patients could be subdivided into four groups: (1) APC mutated polyposis (AFAP), when adenomas were &gt;50 % and APC mutations detected (no. 8, 10 %); (2) MutYH mutated polyposis (MAP), adenomas &gt;50 % and biallelic MutYH mutations (no. 10, 12 %); (1) attenuated polyposis without detectable mutations, prevalence of adenomas, 48 cases (57 %); (1) hyperplastic-serrated polyposis, with prevalence (&gt;50 %) of hyperplastic/other serrated lesions and no constitutional mutation (no. 18, 21 %). Aggregation of tumors, cancer in probands, distribution of polyps and other clinical characteristics showed no difference among the four groups. In conclusions, AFAP and MAP, the polyposis labeled by constitutional mutations, represented about 25 % of all attenuated polyposis. Mutation-associated cases showed an earlier age of onset of polyps and were more frequent in the female sex

Germline TP53 pathogenic variants and breast cancer: A narrative review

Breast cancer; Prognosis; TreatmentCáncer de mama; Pronóstico; TratamientoCàncer de mama; Pronòstic; TractamentApproximately 10% of breast cancers are associated with the inheritance of a pathogenic variant (PV) in one of the breast cancer susceptibility genes. Multiple breast cancer predisposing genes, including TP53, are responsible for the increased breast cancer risk. Tumor protein-53 (TP53) germline PVs are associated with Li-Fraumeni syndrome, a rare autosomal dominant inherited cancer predisposition syndrome associated with early-onset pediatric and multiple primary cancers such as soft tissue and bone sarcomas, breast cancer, brain tumors, adrenocortical carcinomas and leukemias. Women harboring a TP53 PV carry a lifetime risk of developing breast cancer of 80–90%. The aim of the present narrative review is to provide a comprehensive overview of the criteria for offering TP53 testing, prevalence of TP53 carriers among patients with breast cancer, and what is known about its prognostic and therapeutic implications. A summary of the current indications of secondary cancer surveillance and survivorship issues are also provided. Finally, the spectrum of TP53 alteration and testing is discussed. The optimal strategies for the treatment of breast cancer in patients harboring TP53 PVs poses certain challenges. Current guidelines favor the option of performing mastectomy rather than lumpectomy to avoid adjuvant radiotherapy and subsequent risk of radiation-induced second primary malignancies, with careful consideration of radiation when indicated post-mastectomy. Some studies suggest that patients with breast cancer and germline TP53 PV might have worse survival outcomes compared to patients with breast cancer and wild type germline TP53 status. Annual breast magnetic resonance imaging (MRI) and whole-body MRI are recommended as secondary prevention.The project was partially funded by a Gilead Sciences Medical Grant (Fellowship Program 2022) (no grant number)

Robotic-assisted thoracoscopy thymectomy for juvenile myasthenia gravis

Abstract Introduction Juvenile myasthenia gravis (JMG) is a rare debilitating and potentially fatal autoimmune disease, with unclearify pathogenesis. Surgical immunomodulation with thymectomy has been repeatedly demonstrated to be a safe and effective treatment for JMG in both adult and pediatric patients. In the last few years, minimally invasive approach and above all robotic assisted thoracoscopy, replaced sternotomy which is widely used in adult patients. We report our experience in a case of robot-assisted thoracoscopic thymectomy approach in a 12 years old boy for juvenile myasthenia gravis (JMG). Case report Procedure was performed with the Da Vinci surgical robot (Xi) using left-sided approach. Left lung was kept out from mechanic ventilation. A 8 mm port for the 3-D camera was introduced on the V intercostal space on the anterior axillary line. Others two 8mm thoracic ports were placed under vision after the induction of a low-pressure pneumothorax, respectively on the midaxillary line on the III intercostal space and on the parasternal space on the V intercostal space. Bulk resection of gland was made using Maryland grasper and Harmonic scalpel, starting at level of the left pericardiophrenic angle and continuing cranially. Thymus was unstick from the posterior face of the sternum until the right pleura releasing lower thymic horns. After that, controlateral right-side thymectomy was continued into the neck to include the upper horns and finally it was removed with an endocatch bag. Histopathological examination showed a benign thymic hyperplasia. There were no perioperative and postoperative complications. The discharge was on IV post-operative day. After thymectomy, patient reported an improvement in symptoms and stopped medical therapy with pyridostigmine. Conclusions VATS and Robotic thoracoscopic thymectomy have increasingly taken hold in recent years. The surgical treatment offered to patient an improvement in clinical status. Surgery by robotic assistance has demonstrable advantages, including three-dimensional visualization and articulating instruments. Left lateral approach provided excellent visualization of the thymic veins, anonymous vases and phrenic nerves. Three-dimensional visualization as well as articulating arms greatly facilitated the dissection compared with standard thoracoscopic technique. In Literature very few series of robotic approach for surgical treatment of JMG in children are reported, for these reasons further studies are needed