Titanium-coated polypropylene mesh as innovative bioactive material in conservatives mastectomies and pre-pectoral breast reconstruction

Breast reconstruction is rapidly evolving, thanks to the growing acceptance of synthetic meshes as innovative biomaterials. 276 patients undergoing mastectomy (total of 328 mastectomies) were analyzed in a retrospective observational study to evaluate the pre-pectoral immediate breast reconstruction (IBR) using an implant wrapped with Titanium-Coated Polypropylene Mesh (TCPM) vs. patients treated with tissue expander (TE), equally placed pre-pectorally (and wrapped with the same TCPM in 74.3% of the control group’ breasts). 163 patients, of the study group (SG), underwent mastectomy and pre-pectoral IBR with implant wrapped with TCPM, in a one-step surgery, called direct-to-implant technique (DTI), while 113 patients control group (CG) underwent mastectomy and TE. DTI technique has been performed in 192 breasts of the SG while TE procedure in 136 breasts of the CG. The BREAST-Q questionnaire has been provided before the treatment and 2 years later. Baker scale has been used to evaluate capsular contracture. Oncologic, surgical, and aesthetic outcomes along with BREAST-Q scores were analyzed. Additionally, a histologic evaluation was conducted in 11 capsules' samples randomly chosen (6 derived from SG patients and 5 derived from CG). Complications were recorded in 43 cases (29SG-14CG): 8 skin-nipple necrosis (5SG-3CG), 8 wound dehiscence (6SG-2CG), 3 hematomas (1SG-2CG), and 24 infections (8SG-16CG). Grade IV capsular contracture was detected in 9 breasts (1SG-8CG), whereas 254 breasts were grade I (110SG-144CG), 33 (10SG-23CG) grade II, and 32 (4SG-28CG) grade III. Implant wrinkling was detected in 18 cases (10SG-8CG) after 30 months. The local tumor recurrence rate was 5.8%. Three recurrences were on the nipple-areola complex (1.9%). SG patients showed significantly higher rates in the BREAST-Q overall Satisfaction with Outcome (74.1), overall Satisfaction with Breasts (69.1), Psychosocial Well-being (81.9), and Sexual Well-being (63.1), versus CG's patients (p < 0.05). Histological analysis showed a process of normal tissue repair with a complete mesh integration and normal healing. Conservative mastectomies with pre-pectoral IBR assisted by TCPM proved themselves oncologically safe, biologically integrated into native tissues, and highly accepted in terms of quality of life guaranteeing a more natural and aesthetic breast appearance. Core tip: This retrospective observational study provided clinical and histological outcomes of the pre-pectoral IBR using an implant wrapped with TCPM vs. patients treated with TE, equally placed pre-pectorally. The efficacy of IBR using an implant wrapped with TCPM was confirmed by the cosmetic results obtained and by a rate of side effects comparable to TE. All the histological analyses performed confirmed the TCPM mesh complete integration with the physiological aspects of healing: The Collagen 1 and 3 expressions did not differ, between TCPM and NO TCPM samples to confirm a process of healing overlapping to perfect device incorporation and normal healing

Infections in patients with lymphoproliferative diseases treated with targeted agents: SEIFEM multicentric retrospective study

We describe the opportunistic infections occurring in 362 patients with lymphoproliferative disorders treated with ibrutinib and idelalisib in clinical practice. Overall, 108 of 362 patients (29·8%) developed infections, for a total of 152 events. Clinically defined infections (CDI) were 49·3% (75/152) and microbiologically defined infections (MDI) were 50·7% (77/152). Among 250 patients treated with ibrutinib, 28·8% (72/250) experienced one or more infections, for a total of 104 episodes. MDI were 49% (51/104). Bacterial infections were 66·7% (34/51), viral 19·6% (10/51) and invasive fungal diseases (IFD) 13·7% (7/51). Among the 112 patients treated with idelalisib, 32·1% (36/112) experienced one or more infections, for a total of 48 episodes. MDI were 54·2% (26/48). Bacterial infections were 34·6% (9/26), viral 61·5% (16/26) and IFD 3·8% (1/26). With ibrutinib, the rate of bacterial infections was significantly higher compared to idelalisib (66·7% vs. 34·6%; P = 0·007), while viral infections were most frequent in idelalisib (61·5% vs. 19·6%; P < 0·001). Although a higher rate of IFD was observed in patients treated with ibrutinib, the difference was not statistically significant (13·7% vs. 3·8% respectively; P = 0·18). Bacteria are the most frequent infections with ibrutinib, while viruses are most frequently involved with idelalisib

Pathological features and molecular phenotype of mmtv like‐positive feline mammary carcinomas

In the last few years MMTV‐like nucleotide sequences were detected in some feline and canine mammary tumours. Due to the confirmed role of cats in the epidemiology of the MMTV‐like virus, the aim of this study was to investigate the main pathological features of positive feline mammary carcinomas (FMCs). Twenty‐four FMCs were collected at the University of Bologna, submitted to laser microdissection and analysed by nested fluorescence‐PCR using primer sets specific for MMTV env sequence. For immunohistochemistry, an antibody against MMTV protein 14 (p14) was used. MMTV‐like sequences were detected in three out of 24 FMCs (12.5%), one tubular carcinoma, one tubulopapillary carcinoma and one ductal carcinoma. All PCR‐positive tumours were also positive for p14. Multiple nucleotide alignment has shown similarity to MMTV ranging from 98% to 100%. All the 102 examined FMCs were submitted to immunohistochemistry for molecular pheno-typing. Of the nine MMTV‐like positive FMCs, six were basal‐like and three luminal‐like. Our results demonstrate MMTV‐like sequences and protein in FMCs of different geographic areas. Molecular phenotyping could contribute to understand the possible role of MMTV‐like virus in FMC tumor biology

Systemic antifungal treatment after posaconazole prophylaxis: results from the SEIFEM 2010-C survey.

OBJECTIVES: To investigate the incidence, treatment and outcome of breakthrough invasive fungal infections (IFIs) in adult acute myeloid leukaemia (AML) patients after posaconazole prophylaxis. METHODS: From January 2010 to April 2012, all consecutive patients with newly diagnosed AML were prospectively registered at 33 participating Italian centres. All cases of IFIs occurring within 30 days after the end of the first induction chemotherapy were recorded. The strategy of antifungal treatment (empirical, pre-emptive or targeted) and the drugs used were analysed. ClinicalTrials.gov code: NCT01315925. RESULTS: In total, 1192 patients with newly diagnosed AML were enrolled in the study, of whom 510 received posaconazole prophylaxis and were included in the present analysis. Of these patients, 140 (27%) needed systemic antifungal treatment. Among the 127 evaluable cases, an empirical approach was utilized in 102 patients (80%), a pre-emptive approach in 19 patients (15%) and targeted therapy in 6 patients (5%). Only five patients died of IFIs (three in the empirical group and two in the targeted group; 4%). A critical review of IFI diagnoses at 30 days demonstrated that among the patients treated empirically, ∼30% were not affected by IFIs but rather only by fever of unidentified origin. A comparison between the empirical and the pre-emptive groups showed no significant differences regarding the attributable and overall mortalities. CONCLUSIONS: This study confirms that posaconazole prophylaxis reduces the incidence of breakthrough IFIs and does not modify the efficacy of subsequent systemic antifungal treatment, regardless of the approach (empirical or pre-emptive) or the antifungal drug used

Anticancer effects of novel resveratrol analogues on human ovarian cancer cells

Resveratrol, a naturally occurring phytoalexin, has long been known to play an important regulatory role in key functions in cell physiology. This multifunctional role of resveratrol is explained by its ability to interact with several targets of various cell pathways. In the recent past, synthetic chemical modifications have been made in an attempt to enhance the biological effects of resveratrol, including its anti-cancer properties. In this study, we investigated the molecular mechanisms of action of novel trans-restricted analogues of resveratrol in which the C-C double bond of the natural derivative has been replaced by diaryl-substituted imidazole analogues. In ovarian cancer models, the results of in vitro screening revealed that the resveratrol analogues exhibited enhanced anti-proliferative properties compared with resveratrol. We found that the resveratrol analogues also significantly inhibited Akt and MAPK signalling and reduced the migration of IL-6 and EGF-treated cells. Finally, in ascite-derived cancer cells, we demonstrated that the resveratrol analogues reduced the expression of epithelial mesenchymal transition (EMT) markers. Collectively, these findings indicate the enhanced anti-cancer properties of the resveratrol analogues

ANKRd44 gene silencing: A putative role in trastuzumab resistance in HER2-like breast cancer

Trastuzumab is an effective therapeutic treatment for Her2-like breast cancer; despite this most of these tumors develop resistance to therapy due to specific gene mutations or alterations in gene expression. Understanding the mechanisms of resistance to Trastuzumab could be a useful tool in order to identify combinations of drugs that elude resistance and allow a better response for the treated patients. Twelve primary biopsies of Her2+/hormone receptor negative (ER-/PgR-) breast cancer patients were selected based on the specific response to neoadjuvant therapy with Trastuzumab and their whole exome was sequenced leading to the identification of 18 informative gene mutations that discriminate patients selectively based on response to treatment. Among these genes, we focused on the study of the ANKRD44 gene to understand its role in the mechanism of resistance to Trastuzumab. The ANKRD44 gene was silenced in Her2-like breast cancer cell line (BT474), obtaining a partially Trastuzumab-resistant breast cancer cell line that constitutively activates the NF-kb protein via the TAK1/AKT pathway. Following this activation an increase in the level of glycolysis in resistant cells is promoted, also confirmed by the up-regulation of the LDHB protein and by an increased TROP2 protein expression, found generally associated with aggressive tumors. These results allow us to consider the ANKRD44 gene as a potential gene involved in Trastuzumab resistance