The surgical treatment of non-metastatic melanoma in a Clinical National Melanoma Registry Study Group (CNMR): a retrospective cohort quality improvement study to reduce the morbidity rates

Background: Reproducible, high-quality surgery is a key point in the management of cancer patients. Quality indicators for surgical treatment of melanoma has been presented with benchmarks but data on morbidity are still limited. This study presents the quality indicators on morbidity after surgical treatment for non-metastatic skin melanoma in an Italian registry. Methods: Data were extracted from the Central National Melanoma Registry (CNMR) promoted by the Italian Melanoma Intergroup (IMI). All surgical procedures (WE, SNLB or LFND) for non-metastatic skin melanoma between January 2011 and February 2017 were evaluated for inclusion in the study. Only centers with adequate completeness of information (> 80%) were included in the study. Short-term complications (wound infection, dehiscence, skin graft failure and seroma) were investigated. Results: Wound infection rate was 1.1% (0.4 to 2.7%) in WE, 1.3% (0.7 to 2.5%) in SLNB and 4.1% (2.1 to 8.0%) in LFND. Wound dehiscence rate was 2.0% (0.8 to 5.1%) in WE, 0.9% (0.2 to 3.0%) in SLNB and 2.8% (0.9 to 8.6%) in LFND. Seroma rate was 4.2% (1.5 to 11.1%) in SLNB and 15.1% (4.6 to 39.9%) in LFND. Unreliable information was found on skin graft failure. Conclusions: Our findings contribute to available literature in setting up the recommended standards for melanoma centers, thus improving the quality of surgery offered to patients. A consensus on the core issues around surgical morbidity is needed to provide practical guidance on morbidity prevention and management

Evaluating the influence of mechanical stress on anticancer treatments through a multiphase porous media model

Drug resistance is one of the leading causes of poor therapy outcomes in cancer. As several chemotherapeutics are designed to target rapidly dividing cells, the presence of a low-proliferating cell population contributes significantly to treatment resistance. Interestingly, recent studies have shown that compressive stresses acting on tumor spheroids are able to hinder cell proliferation, through a mechanism of growth inhibition. However, studies analyzing the influence of mechanical compression on therapeutic treatment efficacy have still to be performed. In this work, we start from an existing mathematical model for avascular tumors, including the description of mechanical compression. We introduce governing equations for transport and uptake of a chemotherapeutic agent, acting on cell proliferation. Then, model equations are adapted for tumor spheroids and the combined effect of compressive stresses and drug action is investigated. Interestingly, we find that the variation in tumor spheroid volume, due to the presence of a drug targeting cell proliferation, considerably depends on the compressive stress level of the cell aggregate. Our results suggest that mechanical compression of tumors may compromise the efficacy of chemotherapeutic agents. In particular, a drug dose that is effective in reducing tumor volume for stress-free conditions may not perform equally well in a mechanically compressed environment

Diffusivity of propolis compounds in Polylactic acid polymer for the development of anti-microbial packaging films

Correspondance: [email protected] audienceA major research gap is the lack of packaging materials that can provide the release of active compounds at rates suitable for a wide range of food packaging applications. For this reason an anti-microbial/antioxidant release system for food packaging applications was realized by incorporation of propolis into Polylactic acid (PLA) film. The composition of the films was modified by adding polyethylene glycol (PEG) and calcium bentonite (CB) to the initial PIA casting solution; dispersed structures in fact open the molecular network and increase migration rates. The presence of the anti-microbial compound is required essentially at the food surface where the microorganisms are numerous and where they are intended to grow. The diffusivity of four polyphenols was measured in water and ethanol as food simulating liquids (FSL) and the concentration of additives at the interface PLA/Food Simulant was calculated using Fickian models. The external mass transfer coefficient at the interface polymer/FSL could be neglected (with Bi number higher than 200). This is due to the low diffusivity values of propolis polyphenols in the PLA matrix (0.03-0.83 x 10-13 m(2)/s) which lead to a predominant internal mass transfer phenomenon compared to the external one in the system PLA/water. The concentration at interface at equilibrium was different for each substance and depended of the thermodynamical parameter K. Such a delivery system for direct contact with liquid aqueous medium would be a very efficient delivery system because some active agents (polyphenols acids) would be released in relevant quantity in the food whereas others (flavonoids) would remain in the polymer to act at the polymer/food interfac

Water Soluble Molecular Switches of Fluorescence Based on the NiIII/NiII Redox Change

The water soluble NiII complexes of the cyclam derivatives 2 and 3 display the fluorescent emission typical of the covalently linked fluorophores, 1,3 benzodioxole and 1,2,3-trimethoxybenzene, which results from a charge transfer excited state. On oxidation to NiIII, the fluorescence is completely quenched due to the occurrence of an electron transfer (eT) process from the excited fluorogenic fragment Fl* to the oxidized metal. Thus, fluorescence can be switched ON/OFF at will, for several cycles, by consecutively oxidizing and reducing the metal center, in controlled potential electrolysis experiments both in acetonitrile and in aqueous 0.1M HClO4. Occurrence of an eT process from Fl* to NiIII ultimately depends upon the easy oxidation of Fl to Fl+, whereas failure of the occurrence of an eT process from NiII to Fl* has to be ascribed to the particular resistance of Fl fragments to the reduction

An avascular tumor growth model based on porous media mechanics and evolving natural configurations

Mechanical factors play a major role in tumor development and response to treatment. This is more evident for tumors grown in vivo, where cancer cells interact with the different components in the host tissue. Mathematical models are able to characterize the mechanical response of the tumor and can provide a deeper understanding of these interactions. In this work, we present a model for tumor growth based on porous media mechanics. We consider a biphasic system, where tumor cells and the extracellular matrix constitute a solid scaffold, filled with interstitial fluid. A nutrient is dispersed into the fluid phase, supporting the growth of the tumor. The internal reorganization of the tissue in response to external mechanical and chemical stimuli is described by enforcing the multiplicative decomposition of the deformation gradient tensor. In this way, we are able to distinguish the contributions of growth, rearrangement of cellular bonds, and elastic distortion, which occur during tumor evolution. Results are shown for three cases of biological interest, that is growth of a tumor spheroid in (i) culture medium, (ii) host tissue, and (iii) three- dimensional physiological configuration. We report the tumor growth curves for the three cases mentioned above, supplemented with the evolution of quantities of interest, such as the mechanical stresses and interstitial fluid pressures. We analyze the dependence of the tumor development on the mechanical environment, with a particular focus on cell reorganization and its role in stress relaxation. We also address the computational issues of our mathematical model, and discuss the flexibility of the employed numerical implementation. Finally, we speak of further developments, with the scope of providing a deeper understanding of cancer biophysics

Predicting the growth of glioblastoma multiforme spheroids using a multiphase porous media model

Tumor spheroids constitute an effective in vitro tool to investigate the avascular stage of tumor growth. These three-dimensional cell aggregates reproduce the nutrient and proliferation gradients found in the early stages of cancer and can be grown with a strict control of their environmental conditions. In the last years, new experimental techniques have been developed to determine the effect of mechanical stress on the growth of tumor spheroids. These studies report a reduction in cell proliferation as a function of increasingly applied stress on the surface of the spheroids. This work presents a specialization for tumor spheroid growth of a previous more general multiphase model. The equations of the model are derived in the framework of porous media theory, and constitutive relations for the mass transfer terms and the stress are formulated on the basis of experimental observations. A set of experiments is performed, investigating the growth of U-87MG spheroids both freely growing in the culture medium and subjected to an external mechanical pressure induced by a Dextran solution. The growth curves of the model are compared to the experimental data, with good agreement for both the experimental settings. A new mathematical law regulating the inhibitory effect of mechanical compression on cancer cell proliferation is presented at the end of the paper. This new law is validated against experimental data and provides better results compared to other expressions in the literature

A biphasic model for avascular tumor growth and drug response

Tumor spheroids provide an effective in vitro tool to study the early stages of cancer growth. The nutrient and proliferation gradients typical of the avascular stage of tumor development can be reproduced in the laboratory, with a strict control of the environmental conditions. Moreover, current techniques allow to tune the mechanical milieu in which the spheroids are immersed, and evaluate the effects of mechanical stress on tumor development. Remarkably, several studies report a reduction of cell proliferation as a function of increasingly applied stress on the surface of the spheroids. Recently, a computational model based on porous media theory has been proposed to predict tumor growth and its interaction with the host tissue. Inspired by this work, here we report on a specialization of the original model, adapted for tumor spheroids. Starting from standard balance equations for a multiphase system, we close the model with the aid of constitutive relations that are formulated on the basis of experimental observations. In particular, we introduce mathematical expressions describing the mass exchange terms between the different components of the system, and enforce a constitutive relation for the stresses that accounts for the microscopic interactions between the cancer cells. Also, we study the spatiotemporal evolution of a nutrient and of a chemotherapeutic agent over the tumor domain, evaluating their coupled effects on cell proliferation. The spatial discretization of the coupled problem is carried out via the Finite Element Method, and the resulting system is solved with an implicit scheme in COMSOL Multiphysics. A set of experiments is performed to validate the model, investigating the growth of U-87MG spheroids both freely growing in the culture medium and subject to an externally controlled mechanical pressure. Model results are compared to experimental data, showing a good agreement for both the experimental settings. We present a new mathematical law describing the inhibitory effect of mechanical compression on cell proliferation. The new law is validated against the experimental data, providing better results when compared to other expressions in literature

A parametric study of multiphase porous media model for tumor spheroids and envoronment interactions

Computational models for tumor growth provide an effective in silico tool to investigate the different stages of cancer growth. Recently, a series of computational models based on porous media theory has been proposed to predict tumor evolution and its interactions with the host tissue. In addition, a specialization of the original models, adapted for tumor spheroids, has been proposed and validated experimentally. However, due to the complexity of the modeling framework, a systematic understanding of the role of the parameters governing the equations is still lacking. In this work, we perform a parametric analysis on a set of fundamental parameters appearing in the model equations. We investigate the effects of a variation of these coefficients on the spheroid growth curves and, in particular, on the final radii reached by the cell aggregates in the growth saturation stage. Finally, we provide a discussion of the results and give a brief summary of our findings