Breast reconstruction with silicone prosthesis and acellular dermal matrix of porcine origin: Retrospective study of 84 cases.

INTRODUCTION: Breast reconstruction (BR) using a prosthesis implant (PI) associated with an acellular dermal matrix (ADM) is a known method that has been the subject of discussion in recent years. The objective of this study was to quantify the rate of PI removal after BR using prosthesis combined with ADM, and to identify the risk factors in the event of removal. METHODS: This was a retrospective study conducted between 2010 and 2015. Inclusion criteria were patients who had undergone immediate (IBR) or delayed (DBR) breast reconstruction with placement of a PI associated with porcine ADM. The primary endpoint was the postoperative removal of the PI. RESULTS: In all, 84 reconstructions were performed. The mean age of the population was 57.5 years. 25.9% of the patients were active smokers at the time of surgery. 89.5% of patients had previously benefited from ipsilateral breast radiation therapy (IBRT) in DBR, 10.5% in IBR. The PI deposition rate, all BR combined, was 21.4%. It was 52.17% in smokers and 9.84% in non-smokers (P<0.0001), making smoking an independent risk factor for reconstruction failure (hazard ratio (HR)=7.4, 95%CI [2.64-20.9]). IBRT was also a risk factor for PI removal, especially when performed after IBR (HR=8.1, 95%CI [1.1-62.1]). CONCLUSION: Smoking and adjuvant IBRT are risk factors for failure of reconstruction by PI associated with ADM. This type of reconstruction should be selected for non-smokers who have not undergone IBRT and therefore could be a therapeutic alternative in the BR panel.

Effects of nilotinib on leukaemia cells using vibrational microspectroscopy and cell cloning.

Over the last few years, both synchrotron-based FTIR (S-FTIR) and Raman microspectroscopies have helped to better understand the effects of drugs on cancer cells. However, cancer is a mixture of cells with different sensitivity/resistance to drugs. Furthermore, the effects of drugs on cells produce both chemical and morphological changes, the latter could affect the spectra of cells incubated with drugs. Here, we successfully cloned sensitive and resistant leukaemia cells to nilotinib, a drug used in the management of leukaemia. This allowed both the study of a more uniform population and the study of sensitive and resistant cells prior to the addition of the drug with both S-FTIR and Raman microspectroscopies. The incubation with nilotinib produced changes in the S-FTIR and Raman spectra of both sensitive and resistant clones to nilotinib. Principal component analysis was able to distinguish between cells incubated in the absence or presence of the drug, even in the case of resistant clones. The latter would confirm that the spectral differences between the so-called resistant clonal cells prior to and after adding a drug might reside on those more or less sensitive cells that have been able to remain alive when they were collected to be studied with S-FTIR or Raman microspectroscopies. The data presented here indicate that the methodology of cell cloning can be applied to different types of malignant cells. This should facilitate the identification of spectral biomarkers of sensitivity/resistance to drugs. The next step would be a better assessment of sensitivity/resistance of leukaemia cells from patients which could guide clinicians to better tailor treatments to each individual patient.

Chemotherapeutic response to cisplatin-like drugs in human breast cancer cells probed by vibrational microspectroscopy.

Studies of drug-cell interactions in cancer model systems are essential in the preclinical stage of rational drug design, which relies on a thorough understanding of the mechanisms underlying cytotoxic activity and biological effects, at a molecular level. This study aimed at applying complementary vibrational spectroscopy methods to evaluate the cellular impact of two Pt(ii) and Pd(ii) dinuclear chelates with spermine (Pt2Spm and Pd2Spm), using cisplatin (cis-Pt(NH3)2Cl2) as a reference compound. Their effects on cellular metabolism were monitored in a human triple-negative metastatic breast cancer cell line (MDA-MB-231) by Raman and synchrotron-radiation infrared microspectroscopies, for different drug concentrations (2-8 µM) at 48 h exposure. Multivariate data analysis was applied (unsupervised PCA), unveiling drug- and concentration-dependent effects: apart from discrimination between control and drug-treated cells, a clear separation was obtained for the different agents studied - mononuclear vs. polynuclear, and Pt(ii) vs. Pd(ii). Spectral biomarkers of drug action were identified, as well as the cellular response to the chemotherapeutic insult. The main effect of the tested compounds was found to be on DNA, lipids and proteins, the Pd(ii) agent having a more significant impact on proteins while its Pt(ii) homologue affected the cellular lipid content at lower concentrations, which suggests the occurrence of distinct and unconventional pathways of cytotoxicity for these dinuclear polyamine complexes. Raman and FTIR microspectroscopies were confirmed as powerful non-invasive techniques to obtain unique spectral signatures of the biochemical impact and physiological reaction of cells to anticancer agents.

Biomolecular characterization of adrenal gland tumors by means of SR-FTIR.

The adrenal glands are small endocrine organs located on the bottom pole of each kidney. Anatomically they are composed of cortical and medullar parts. Due to dysfunctional processes they can transform into the pathological lesions (in both cortex and medulla). The incidentally detected adrenal lesions have become an arising clinical problem nowadays. The crucial issue for an accurate treatment strategy is relevant diagnosis. Distinguishing between benign and malignant lesions is often difficult during the standard histological examination. Hence the alternative methods of differentiation are investigated. One of them is Fourier transform infrared spectroscopy which allows the analysis of the biomolecular composition of the studied tissue. In this paper we present the very preliminary FTIR studies for defining the biomolecular pattern of three types of adrenal lesions: adenoma (AA) and adrenal cortical hyperplasia (ACH) - both derived from adrenal cortex as well as pheochromocytoma (PCC) - from the medullar part of the gland. All studied cases were classified as benign lesions. The general observations show that cortically derived tissues are rich in lipids and they are rather protein depleted while for medullar pheochromocytoma there is the opposite relationship. Furthermore, the unequivocal differences were noticed within the "fingerprinting" range. In addition subtle shifts in absorption band positions were observed between studied cases.

Unsupervised explorative data analysis of normal human leukocytes and BCR/ABL positive leukemic cells mid-infrared spectra.

We proved the ability of Fourier Transform Infrared microspectroscopy (microFTIR) complemented by Principal Component Analysis (PCA) to detect protein phosphorylation/de-phosphorylation in mammalian cells. We analyzed by microFTIR human polymorphonuclear neutrophil (PMNs) leukocytes, mouse-derived parental Ba/F3 cells (Ba/F3#PAR), Ba/F3 cells transfected with p210(BCR/ABL) (Ba/F3#WT) and expressing high levels of protein tyrosine kinase (PTK), and human-derived BCR/ABL positive K562 leukemic cell sub-clones engineered to differently express receptor-type tyrosine-protein phosphatase gamma (PTPRG). Synchrotron radiation (SR) and conventional (globar) IR sources were used to perform microFTIR respectively, on single cells and over several cells within the same sample. Ex vivo time-course experiments were run, inducing maximal protein phosphorylation in PMNs by 100 nM N-formylated tripeptide fMLP. Within the specific IR fingerprint 1800-850 cm(-1) frequency domain, PCA identified two regions with maximal signal variance. These were used to model and test the robustness of PCA in representing the dynamics of protein phosphorylation/de-phosphorylation processes. An IR signal ratio marker reflecting the homeostatic control by protein kinases and phosphatases was identified in normal leukocytes. The models identified by microFTIR and PCA in normal leukocytes also distinguished BCR/ABL positive Ba/F3#WT from BCR/ABL negative Ba/F3#PAR cells as well as K562 cells exposed to functionally active protein tyrosine phosphatase recombinant protein ICD-Tat transduced in cells by HIV-1 Tat technology or cells treated with the PTK inhibitor imatinib mesylate (IMA) from cells exposed to phosphatase inactive (D1028A)ICD-Tat recombinant protein and untreated control cells, respectively. The IR signal marker correctly reflected the degrees of protein phosphorylation associated with abnormal PTK activity in BCR/ABL positive leukemic cells and in general was inversely related to the expression/activity of PTPRG in leukemic sub-clones. In conclusion, we have described a new, reliable and simple spectroscopic method to study the ex vivo protein phosphorylation/de-phosphorylation balance in cell models: it is suitable for biomedical and pharmacological research labs but it also needs further optimization and its evaluation on large cohorts of patients to be proposed in the clinical setting of leukemia.

COMPLETE REMISSION OF MEDICALLY TREATED LUTEINIZED THECOMAS WITH SCLEROSING PERITONITIS.

We describe the first French patient treated for sclerosing peritonitis syndrome associated with lutheinized thecomas. At 42 years old, she had respiratory distress with increased abdominal volume. Physical examination revealed ascites, pleural effusions, and two mobile latero-uterine masses. Radiological examinations revealed bilateral ovarian masses of 10 cm. Bilateral adnexectomy was performed by laparotomy. Histological analysis concluded that there were benign luteinized thecomas. Until the 36th postoperative day, the general condition of the patient deteriorated to become critical. A second surgical procedure was attempted revealing sclerosing fibrosis preventing access to the peritoneal cavity. Subsequently, a medical treatment combining parenteral nutrition, high intravenous doses of corticosteroids, antiestrogens, colchicine and sandostatin was administered and effective allowing continuity recovery 15 months later. The clinical outcomes has been favorable at 24 month later.