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Abstract Background High-grade serous ovarian cancer is a detrimental disease. Treatment options in patients with a recurrent disease are dependent on BRCA1/2 mutation status since only patients with known BRCA mutation are eligible for treatment with poly(ADP-ribose) polymerase inhibitors (PARPi). The aim of this study was to compare concordance of BRCA mutation analyses from cytological samples (CS) with BRCA mutation analyses from histological formalin fixed paraffin embedded (FFPE) samples. Methods Mutation analysis of BRCA1 and BRCA2 genes was performed in 44 women diagnosed with primary or recurrent high-grade ovarian cancer from three different samples: blood, cytological sample (ascites, pleural effusion and enlarged lymph nodes) and tumor tissue. Results from all three samples were compared. Results Among 44 patients, there were 15 germline mutations and two somatic mutations. A 100% concordance was found between cytological and histologic samples. Conclusion There is a 100% concordance in BRCA mutation testing between cytological and histologic samples. BRCA mutation testing from CS could replace testing from FFPE tissue in clinical decision making in ovarian cancer patients. Trial registration The study was retrospectively registered at ISRCTN registry on 24/11/2015 - ISRCTN42408038.

Tumble drying of textiles is associated with mechanical and thermal stress, which leads to textile damage and shedding of fibers. In this study, fiber shedding from cotton textiles is investigated by evaluating the mass of fibers accumulated on different filters positioned downstream of the tumble dryer drum. The total mass of fibers at the end of drying was positively correlated with the dry mass of the loaded textiles. By observing the time-dependent accumulation of fibers on a high-performance filter, three different phases of fiber shedding could be identified. In the first phase, which lasted up to a textile moisture content of about 35%, only minimal fiber accumulation was detected. The following phase lasted almost until the end of drying and showed the highest fiber accumulation rates. In the last phase, the rate of fiber accumulation decreased. The experiments also showed that longer tumbling of textiles with a lower moisture content led to a greater total mass of accumulated fibers. To reduce fiber shedding, damage to the textiles and the resulting pollution, it is recommended to reduce the mechanical loading of textiles, especially in the final stages of the drying process.

Cavitation erosion is one of the most severe problems encountered in hydraulic turbomachinery. When testing the materials, the engineers usually rely on standardized procedures. The most common one being the vibratory ASTM G-32 test, which offers two possibilities of performing the test – the direct, where the specimen is attached to the ultrasonic device and the indirect, where the specimen is stationary and exposed to the ultrasonic horn, positioned just 0.5 mm from it. The erosion rates from the two are significantly different and a question may be asked if they are at all comparable and further on are they comparable to the “real-life” hydrodynamic cavitation which occurs in turbomachinery.In this study we performed erosion tests on a stationary specimen where the gap between the specimen and the horn was varied from 0.3 to 4 mm. In addition, we used high speed visualization to observe the cavitation in the gap.We observed that the cavitation erosion rate strongly depends on the gap. From visualization we see that the cavitation dynamics significantly changes in a small gap, leading to a large, but 2-dimensional cavitation bubbles which collapse very slowly, compared to the small spherical ones in a larger gap.We investigated the probability of shock wave occurrence and derived a very simple model, which gives accurate qualitative predictions of experimental data.Finally, the study puts into question the validity of ASTM G32 test – the most common approach used in engineering today.

Incidenca melanoma v svetu in Sloveniji še vedno narašča, se je pa preživetje v zadnjih 20 letih izboljšalo, predvsem zaradi zgodnejšega odkrivanja melanoma in enotnih pristopov v primarnem zdravljenju. Posodobljena Priporočila v letu 2024 prinašajo precej novosti, predvsem v diagnostičnih postopkih odkrivanja in zamejitve zgodnjih stadijev melanoma, kot tudi natančnih priporočil sledenja po primarnem zdravljenju, na področju kirurškega zdravljenja in pa predvsem sistemskega zdravljenja, tako metastatske bolezni, predvsem pa v adjuvan- tnem sistemskem zdravljenju v visoko rizičnem stadiju II, in neo- adjuvantnem sistemskem zdravljenju operabilnega melanoma. V tokratna Priporočila smo vključili tudi poglavji prehranskega in paliativnega tima.

Abstract Different applications or industries use different systems for linear actuation, such as hydraulic, pneumatic or electric. Electric systems are becoming increasingly popular and are already replacing hydraulic systems in various applications. These are known to be potentially harmful to the environment, as large amounts of fluid can be released into the environment in the event of a pipe burst or other accident. This paper presents the results of a comparison between hydraulic, pneumatic and electric systems under variable conditions but with similar loads in all three systems. The common feature of all three systems is the input power, which was limited to 1.1 kW. There was no hydraulic accumulator in the hydraulic system and no pressure vessel in the pneumatic system, so no stored energy could influence the system behaviour or results. The main difference between the systems studied was the profile of displacement and power consumption. The most consistent response and lowest power consumption were obtained with the electric system, although both hydraulic and pneumatic systems can achieve consistent response with some modifications.

Small-scale vegetable producers often do not have modern mechanical equipment; as a result, a significant amount of inter-row and all intra-row weeding is performed manually. The development of small, affordable machines increases the competitiveness of organic vegetable production, improves sustainable land use, and reduces dependence on unwanted herbicides. In this study, a simple modular lightweight e-hoe with the capability for both inter-row (1st degree of freedom) and intra-row (2nd degree of freedom) weeding was proposed. The e-hoe uses battery-powered in-wheel drives to move the platform (3rd degree of freedom) and additional drives to operate the tools. The e-hoe was evaluated in a small greenhouse using three different tools: a traditional hoe, an adjusted rounded hoe, and an adjusted spring tine narrow hoe. The experiments were conducted at four different tool rotation speeds, using specially designed 3D-printed models for crops and weeds for evaluation. The results indicate that the efficiency of the e-hoe rates up to 95% when the right tool design and rotation speed are combined. Based on the battery capacity, the machine can be operated for approximately 3.7 h, enabling the weeding of about 3050 plants.

Design of open channel transport and flow measurement systems for highly viscous liquids requires accurate modelling of laminar free overfall. In this study, a computational fluid dynamics model was developed to investigate subcritical laminar free overfall in smooth horizontal channels with 90° isosceles triangle cross-section. Volume of fluid-based simulations were performed at different liquid discharges and viscosities, with Reynolds numbers at normal uniform depth between 5.5 and 139. Simulation results were in good agreement with verification experiments, indicating development of laminar velocity magnitude profiles while gauge pressure profiles resemble hydrostatic distribution except near the brink. The end-depth-ratio ranged between 0.80 and 0.96, reducing towards values reported for turbulent free overfall in the highest Reynolds number simulation. Existing models for critical depth, end depth discharge and free overfall jet trajectories were in satisfactory agreement above Re = 10, while producing larger deviations below this threshold due to increased viscous effects.

This paper presents a photogrammetry-based system for capturing turbulent aerated flow topography in a laboratory environment, especially for complex hydraulic phenomena character-ised by turbulent, non-stationary, and non-homogeneous aerated flows. It consists of ten high-resolution cameras equipped with monochromatic sensors and custom-built LED lights, all synchronised for accurate data acquisition. Post processing involves Structure-from-Motion and Multi-View Stereo techniques to calculate exterior and interior orientation parameters that ensure accurate alignment within a desired coordinate system, and conversion to point clouds. The proposed method showed great potential for capturing free water surface topography of turbulent aerated flows with high spatial and temporal resolution over the entire field of view of the cameras. Due to the unique capabilities of this system, direct comparisons with existing benchmarks were not possible. Instead, average free water surface profiles were derived from selected control cross sections, using 2D LIDAR measurements for verification. Both the LIDAR and photogrammetry averaged profiles showed remarkably good agreement, with deviations within ±20 mm. Validation showed that photogrammetry can be used to measure the complex aerated turbulent free water surface. In this way, this approach, involving consecutive image dataset acquisition at predefined intervals, is proving to be a valuable tool for observing, visualising, analysing, investigating, and gaining a comprehensive understanding of the dynamics of the free water surface.

Acoustic cavitation, generated by a piezo-driven transducer, is a commonly used technique in a variety of processes, from homogenization, emulsification, and intensification of chemical reactions to surface cleaning and wastewater treatment. An ultrasonic horn, the most commonly used acoustic cavitation device, creates unique cavitation conditions under the horn tip that depend on various parameters such as the tip diameter, the driving frequency of the horn, its amplitude, and fluid properties. Unlike for hydrodynamic cavitation, the scaling laws for acoustic cavitation are poorly understood. Empirical relationships between cavitation dynamics, ultrasonic horn operating conditions, and fluid properties were found through systematic characterization of cavitation under the tip. Experiments were conducted in distilled water with various sodium chloride salt concentrations under different horn amplitudes, tip geometries, and ambient pressures. Cavitation characteristics were monitored by high-speed (200,000 fps) imaging, and numerous relations were found between operating conditions and cavitation dynamics. The compared results are discussed along with a proposal of a novel acoustic cavitation parameter and its relationship to the size of the cavitation cloud under the horn tip. Similar to the classical hydrodynamic cavitation number, the authors propose for the first time an acoustic cavitation parameter based on experimental results.

Abstract Background Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited. Methods Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates. Results A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis. Conclusions Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families.

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The blade outlet angle, wrap angle, and number of blades of the impeller are optimized to increase the pumping efficiency of the automotive coolant pump while keeping the size constant. Three new variants were designed and the optimal one was selected for the comparison with the original scheme. The experiment was conducted to test the hydraulic performance of the optimized impeller. The results show that the energy characteristics of the optimized impeller are in reasonable agreement with the experimental data. The energy characteristics and internal flow details of original scheme and optimized scheme are analyzed and compared. It was found that increasing the wrap angle while decreasing blade outlet angle appropriately can improve the flow conditions and the pressure distribution in the impeller and the volute, especially at low flow rates. At the designed flow rate, increasing the wrap angle while decreasing the number of blades and blade outlet angle can significantly increase the efficiency of the pump. And the maximum efficiency of the optimized impeller is 4.8% higher than the efficiency of the original impeller. The results of the study can guide designers in optimizing an automotive centrifugal coolant pump and reduce energy consumption of the automotive cooling system.

Turbulent free-surface flows are encountered in several engineering applications and are typically characterized by the entrainment of air bubbles due to intense mixing and surface deformation. The resulting complex multiphase structure of the air–water interface presents a challenge in precise and reliable measurements of the free-water-surface topography. Conventional methods by manometers, wave probes, point gauges or electromagnetic/ultrasonic devices are proven and reliable, but also time-consuming, with limited accuracy and are mostly intrusive. Accurate spatial and temporal measurements of complex three-dimensional free-surface flows in natural and man-made hydraulic structures are only viable by high-resolution non-contact methods, namely, LIDAR-based laser scanning, photogrammetric reconstruction from cameras with overlapping field of view, or laser triangulation that combines laser ranging with high-speed imaging data. In the absence of seeding particles and optical calibration targets, sufficient flow aeration is essential for the operation of both laser- and photogrammetry-based methods, with local aeration properties significantly affecting the measurement uncertainty of laser-based methods.

For successful dosing of plant protection products, the characteristics of the vine canopies should be known, based on which the spray amount should be dosed. In the field experiment, we compared two optical experimental methods, terrestrial lidar and aerial photogrammetry, with manual defoliation of some selected vines. Like those of other authors, our results show that both terrestrial lidar and aerial photogrammetry were able to represent the canopy well with correlation coefficients around 0.9 between the measured variables and the number of leaves. We found that in the case of aerial photogrammetry, significantly more points were found in the point cloud, but this depended on the choice of the ground sampling distance. Our results show that in the case of aerial UAS photogrammetry, subdividing the vine canopy segments to 5 × 5 cm gives the best representation of the volume of vine canopies.

This paper describes the process of 3D analysis of two water currents with method of photogrammetry. Photogrammetry is used in fields such as architecture, engineering, police investigation, preserving cultural heritage, military and geology. This method can be used in military to reconstruct a site with traces of shrapnel or various projectiles. In our case we tried to measure height of turbulent flow, where two currents collided at the angle of 90°. In first section we introduce our problem and method. Second section describes method of photogrammetry and basics of torrential flows. In third section we describe our experiment. Fourth section describes the course of getting 3D model. In fifth section we analyze results and in sixth section, a conclusion is given.

The research on the potential of cavitation exploitation is currently an extremely interesting topic. To reduce the costs and time of the cavitation reactor optimization, nowadays, experimental optimization is supplemented and even replaced using computational fluid dynamics (CFD). This is a very inviting opportunity for many developers, yet we find that all too often researchers with non-engineering background treat this “new” tool too simplistic, what leads to many misinterpretations and consequent poor engineering.The present paper serves as an example of how complex the flow features, even in the very simplest geometry, can be, and how much effort needs to be put into details of numerical simulation to set a good starting point for further optimization of cavitation reactors. Finally, it provides guidelines for the researchers, who are not experts in computational fluid dynamics, to obtain reliable and repeatable results of cavitation simulations.

Tumbling Multi-Chamber (TMC) gear pump is a generally unknown type of hydraulic device, which features a unique three-dimensional shape of the gears. The main benefits of such design over the conventional gear pumps are self-adapting tightness of the pump parts, the possibility to mold the parts from a polymer material and high volumetric efficiency, considering the simplicity of the design. The specific working principle of TMC pumps requires a slightly different approach to the numeric modeling and analysis process compared to the conventional gear pump types (e.g. external gear and gerotor pumps). One of the main contributions of the work is the development of an analysis procedure, which allows studying flow and pressure conditions in the TMC pump. This includes the influence of the positioning of the pump parts on spatial and temporal variations in sealing regions and the influence of pressure field propagation in relation to the valve plate position.

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V preteklosti so bolnike z zasevki po peritoneju obravnavali kot neozdravljivo bolne s terminalnim stanjem raka, ki se zdravi samo paliativno. Ob takšnem pristopu je bilo povprečno preživetje bolnikov le dva meseca. Zdravljenje teh bolnikov se je v devetdesetih letih prejšnjega stoletja pomembno spremenilo. Nekateri raziskovalci so bili namreč mnenja, da so peritonealni zasevki v določenih primerih samo vrsta loko-regionalne bolezni in se bolnik lahko (p)ozdravi. Eden glavnih zagovornikov te teorije in novega načina zdravljenja je bil Paul Sugarbaker. V sklopu zdravljenja se je začela uporabljati citoreduktivna kirurgija v kombinaciji z intraperitonealno kemoterapijo. Namen kirurškega posega je bila makroskopska odstranitev tumorja, nato pa z intraperitonealno kemoterapijo odstranitev še morebitnih mikroskopskih “preostankov” bolezni. Postopek, pri katerem citostatik med operacijo uvedemo in segrevamo, se imenuje hipertermična intraperitonealna kemoterapija. Hipertermija ima že sama po sebi protitumorski učinek na maligne celice, saj povzroči razgradnjo proteinov, aktivranje lizosomov in apoptozo. Ob segrevanju raztopine citostatika potečejo zapletene kemijske reakcije, ki dodatno povečajo njegovo učinkovitost in povečajo globino prodiranja zdravila v tumorsko tkivo. O najboljših rezultatih te oblike zdravljenja so poročali v primerih psevdomiksoma peritoneja, raka debelega črevesa in danke, karcinoma slepiča, karcinoma jajčnikov in peritonealnega mezotelioma. V prispevku avtorji predstavijo to zahtevno metodo zdravljenja, indikacije in vključitvena merila bolnikov ter sodobna spoznanja o učinkovitosti te metode za določene vrste raka.

Slovenia is a Central European country with a long history of hydropower. This paper gives a brief introduction to the current status of hydropower utilization and informs about some selected successful examples of hydropower plant operation. One such example is fish passage and flood risk reduction on the lower reaches of the Sava River at the Brežice hydroelectric power plant, taking into account a complex of morphological, hydrological, hydraulic, and anthropogenic factors. Future development is considered against the background of the National Energy and Climate Plan, which does not envisage any significant expansion in the capacity or function of the hydropower sector. The envisaged capacity increase is from the current 4430 GWh to around 4580 GWh by 2030. It is shown that the current energy storage capacity of Slovenia’s only pumped storage plant will be sufficient to offset the introduction of new non-dispatchable renewable energy sources by 2030. By around 2028, the country will have a need for electrical energy storage from renewable energy sources, reaching a modest total of only 6140 MWh per year. However, by sticking to the unambitious National Energy and Climate Plan, Slovenia will miss the opportunity to remain self-sufficient in electricity generation and significantly increase its share of renewable energy sources. The National Energy and Climate Plan aims to increase the share of renewable energy in total energy generation from 25% in 2020 to 27% by 2030.

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The influence of a bulb runner blade hydrofoil shape on flow characteristics around the blade was studied. Experimental work was performed on a bulb turbine measuring station and a single hydrofoil in a cavitating tunnel. In the cavitation tunnel, flow visualization was performed on the hydrofoil’s suction side. Cavitation structures were observed for several cavitation numbers. Cavitation was less intense on the modified hydrofoil than on the original hydrofoil, delaying the cavitation onset by several tenths in cavitation number. The results of the visualization in the cavitation tunnel show that modifying the existing hydrofoil design parameters played a key role in reducing the cavitation inception and development, as well as the size of the cavitation structures. A regression model was produced for cavitation cloud length. The results of the regression model show that cavitation length is dependent on Reynolds’s number and the cavitation number. The coefficients of determination for both the existing and modified hydrofoils were reasonably high, with R2 values above 0.95. The results of the cavitation length regression model also confirm that the modified hydrofoil exhibits improved the cavitation properties.

Recently the development of Kelvin-Helmholtz instability in cavitating flow in Venturi microchannels was discovered. Its importance is not negligible, as it destabilizes the shear layer and promotes instabilities and turbulent eddies formation in the vapor region, having low density and momentum. In the present paper, we give a very brief summary of the experimental findings and in the following, we use a computational fluid dynamics (CFD) study to peek deeper into the onset of the Kelvin-Helmholtz instability and its effect on the dynamics of the cavitation cloud shedding. Finally, it is shown that Kelvin-Helmholtz instability is beside the re-entrant jet and the condensation shock wave the third mechanism of cavitation cloud shedding in Venturi microchannels. The shedding process is quasi-periodic.

In the process of applying a plant protection product mixed with water (spray mixture) at the prescribed concentration with conventional sprayers for chemical protection of tree canopies in an orchard, standard models are used to express the dose rate of the plant protection product. Characteristic properties of the tree canopy in an orchard are not taken into consideration. Such models result in fixed quantities of spray mixture being sprayed through individual nozzles into a tree canopy. In this research work, an autonomous system is presented, which ensures a controlled quantity of spray mixture sprayed through the nozzles onto different tree canopy segments. The autonomous system is based on a fuzzy logic system (FLS) that includes information about the estimated leaf area to ensure more appropriate control of the spray mixture. An integral part of the FLS is a fuzzy logic controller for three electromagnetic valves operating in the pulse width mode and installed on the axial sprayer prototype. The results showed that, with the FLS, it was possible to control the quantity of spray mixture in the specific range depending on the estimated value of the leaf area, with a quantitative spray mixture average saving of 17.92%. For the phenological growth stage BBCH 91, this method represents a powerful tool for reducing the quantity of spray mixture for plant protection in the future.

The article explores Mao’s conception of the revolutionary subject, focusing on the relationship between the peasantry and proletariat. In the years after the October Revolution, when vulgar and reductionist readings and interpretations of Marx seemed to prevail, Mao, influenced by the specific material conditions and class relations in China, conceptualised an important novelty within the Marxist tradition. Namely, he developed a very different and original understanding of the revolutionary subject, and especially a different understanding of the relationship between the proletariat and peasantry. He introduced the split between the main revolutionary subject––the proletariat––and the main revolutionary force––the peasantry. This novelty, which was unique up to that point in Marxist theory, enabled Mao to think of the Chinese revolutionary movement within a Marxist framework while considering the material conditions of life in China.

Image registration is the process of aligning two or more images of the same scene taken at different times; from different viewpoints; and/or by different sensors. This research focuses on developing a practical method for automatic image registration for agricultural systems that use multimodal sensory systems and operate in natural environments. While not limited to any particular modalities; here we focus on systems with visual and thermal sensory inputs. Our approach is based on pre-calibrating a distance-dependent transformation matrix (DDTM) between the sensors; and representing it in a compact way by regressing the distance-dependent coefficients as distance-dependent functions. The DDTM is measured by calculating a projective transformation matrix for varying distances between the sensors and possible targets. To do so we designed a unique experimental setup including unique Artificial Control Points (ACPs) and their detection algorithms for the two sensors. We demonstrate the utility of our approach using different experiments and evaluation criteria.

Isolated limb perfusion is a surgical procedure that can be used to treat an advanced malignant melanoma and soft tissue sarcomas, it is also effective in treating in-transit metastases of melanoma and local metastases of soft tissue sarcomas. With perfusion of the affected limb with cytostatic agents it is possible to avoid amputation and mutilating operations that significantly reduced the function of the limb. Since the procedure is isolated on a limb, it can be perfused with much higher doses of cytotoxic drugs, systemic toxicity is thus reduced or prevented. The most common side effects are erythema and edema.Cytotoxic drugs, that are manly used, are melphalan and tumor necrosis factor alpha. Efficient also proved to be simultaneous hyperthermia of the affected limb.

This research demonstrates the basic elements of a prototype automated orchard sprayer which delivers pesticide spray selectively with respect to the characteristics of the targets. The density of an apple tree canopy was detected by PROWAVE 400EP250 ultrasound sensors controlled by a Cypress PSOC CY8C29466 microcontroller. The ultrasound signal was processed with an embedded computer built around a LPC1343 microcontroller and fed in real time to electro-magnetic valves which open/close spraying nozzles in relation to the canopy structure. The analysis focuses on the detection of appropriate thresholds on 15 cm ultrasound bands, which correspond to maximal response to tree density, and this was selected for accurate spraying guidance. Evaluation of the system was performed in an apple orchard by detecting deposits of tartrazine dye (TD) on apple leaves. The employment of programmable microcontrollers and electro-magnetic valves decreased the amount of spray delivered by up to 48.15%. In contrast, the reduction of TD was only up to 37.7% at some positions within the tree crown and 65.1% in the gaps between trees. For all these reasons, this concept of precise orchard spraying can contribute to a reduction of costs and environmental pollution, while obtaining similar or even better leaf deposits.

Da bi pravočasno odkrili zasevke kožnega melanoma (KM), na Onkološkem inštitutu Ljubljana uporabljamo določanje serumske ravni tumorskega označevalca S100B. Če je raven zvišana, nadaljujemo s slikovnimi preiskavami, v zadnjih letih predvsem s PET-CT. S svojo raziskavo smo skušali pokazati, kako učinkovito je odkrivanje napredovale bolezni z določanjem serumskega S100 B in s PET-CT med rednim sledenjem bolnikov, ki imajo KM. Med septembrom 2007 in februarjem 2010 smo na PET-CT napotili 115 bolnikov s KM. Med njimi je bilo 82 (71,3 %) bolnikov s kliničnimi znaki bolezni in 33 (28,7 %) asimptomatskih bolnikov z 2 povečanima vrednostma serumskega S100 B. Z uveljavljenimi metodami smo izračunali občutljivost, specifičnost ter pozitivno in negativno napovedno vrednost (PNV, NNV) določanja S100 B in PET-CT. Zasevke smo odkrili pri 81,7 % bolnikov. Občutljivost, specifičnost, PNV in NNV S100 B so bili 33,8 %, 90,9 %, 96 % in 17,5 % pri bolnikih s kliničnimi znaki bolezni. Pri 20 % bolnikov so bile povečane serumske vrednosti S100 B edini znanilec zasevkov KM. Občutljivost in PNV S100 B v tej skupini bolnikov sta bila 100 % in 69,7 %. S PET-CT smo napredovalo bolezen potrdili pri 84,2 % bolnikov, ki so imeli klinično sliko napredovale bolezni, ter pri 72,7 % asimptomatskih bolnikov s povečanimi vrednostmi S100 B. Občutljivost, specifičnost, PNV in NNV PET-CT za bolnike s klinično sliko so bili 98,5 %, 90,9 %, 98,5 %, 90,9 % ter 100 %, 90 %, 95,8 % in 100 % pri asimptomatskih bolnikih s povečanimi vrednostmi S100 B. Redno spremljanje serumskega S100 B pri bolnikih s KM omogoča odkritje napredovale bolezni pri asimptomatskih bolnikih. Uspešnost metode je večja, če bolnike napotimo na PET-CT, kadar imajo povečane vrednosti S100 B.

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Gensko testiranje za dedno obliko malignega melanoma kože na OI Ljubljana opravljamo od leta 2005. Izbor bolnikov za testiranje poteka v okviru genetskega svetovanja. Testiramo bolnike in njihove zdrave sorodnike, če sta v družini najmanj dva obolela člana, in bolnike s primarnimi multiplimi melanomi brez obremenjujoče družinske anamneze. Na oddelku za molekularno diagnostiko z metodo sekvenčne analize iščemo in določamo neznane točkovne mutacije ter manjše delecije in insercije v eksonih genov, povezanih z nastankom malignega melanoma kože: CDKN2A, CDK4 in MC1R. Do sedaj smo testirali 70 oseb: 40 bolnikov in njihovih zdravih sorodnikov iz 28 različnih družin, obremenjenih z družinsko anamnezo, ter 30 bolnikov s primarnimi multiplimi melanomi. Sekvenčna analiza genov, povezanih z dedno obliko malignega melanoma kože, je pokazala, da so mutacije CDKN2A p16INK4a pri bolnikih z družinsko anamnezo zelo pogoste (37,5 %). Mutacij CDKN2A p14ARF in CDK4 pri slovenskih bolnikih nismo našli.

Kožni melanom je z vidika zdravljenja kirurška bolezen, saj kirurgija predstavlja zelo pomemben način zdravljenja pri vseh stadijih bolezni. Ločimo kirurško zdravljenje primarne lezije, regionalnih, in-transit in oddaljenih zasevkov. Pri primarni leziji ločimo diagnostično in široko (radikalno) ekscizijo. Varnostni rob je pri prvi do 5 mm, pri drugi pa med 1 do 2 cm, odvisno od debeline melanoma. Pri regionalnih zasevkih melanoma govorimo glede na njihovo velikost o klinično okultnih in klinično prepoznavnih zasevkih. Prve ugotovimo s pomočjo biopsije sentinel bezgavke in jih nato zdravimo tako kot klinično prepoznavne zasevke z radikalno limfadenektomijo regionalne bezgavčne lože. In-transit zasevke lahko zdravimo s preprosto ekscizijo ali pa v primerih, ko jih je več in so locirani na ekstremitetah s pomočjo tehnično zahtevnih izolirane ekstremitetne perfuzije ali infuzije. Pri sistemskem razsoju je kirurško zdravljenje vedno prvi izbor zdravljenja, v kolikor je možno zasevke odstraniti v celoti.

Izolirana ekstremitetna perfuzija (ILP) je oblika regionalnega zdravljenja napredovalih rakov udov. Prvič je bila opisana v 50. letih prejšnjega stoletja in se je s časom nadgrajevala. Tako so v 80. letih najprej dodali hipertermijo, v 90. letih pa še citokin TNF (tumor necrosis factor). Danes z ILP zdravimo bolnike z lokoregionalno napredovalim melanomom (intranzit zasevki) in sarkomi, pri katerih bi bila za radikalnost potrebna amputacija uda. Pri posegu izoliramo arterijo in veno za spodnji oz. zgornji ud in ju priključimo na napravo za zunajtelesni krvi obtok, s čimer ud izoliramo od sistemskega krvnega obtoka. Ud nato segrejemo na temperaturo okoli 40 o C in z izotopno metodo izključimo komunikacijo med izoliranim obtokom uda in sistemskim obtokom. Če med sistemoma ne uhaja tekočina, apliciramo citostatik. Koncentracija citostatika v izoliranem sistemu je 10- do 20-krat večja, kot je zaradi neželenih učinkov možno pri sistemski aplikaciji. Po posegu ud izperemo, zašijemo arterijo in veno ter ga znova priključimo na sistemski krvni obtok. Pooperativni zapleti so večinoma omejeni na ud in so navadno blagi (eritem in edem). Pri bolnikih z melanomom dosežemo popolni odgovor pri približno 70 % bolnikov, pri bolnikih s sarkomi pa nam omenjeni poseg omogoči ohranitev uda pri 80 % bolnikov, pri katerih bi bila sicer potrebna amputacija.