Kristijan Skok
@pathologie.medunigraz.at
Diagnostic and Research Institute of Pathology, Medical University Graz
Diagnostic and Research Institute of Pathology, Medical University Graz
RESEARCH, TEACHING, or OTHER INTERESTS
Pathology and Forensic Medicine, Medicine, Critical Care and Intensive Care Medicine, Pathophysiology
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Marko Gosak, Marko Milojević, Maja Duh, Kristijan Skok, and Matjaž Perc
Elsevier BV
Tanja Zidarič, Kristijan Skok, Kristjan Orthaber, Matevž Pristovnik, Lidija Gradišnik, Tina Maver, and Uroš Maver
MDPI AG
This study presents an innovative wound dressing system that offers a highly effective therapeutic solution for treating painful wounds. By incorporating the widely used non-steroidal anti-inflammatory drug diclofenac, we have created an active wound dressing that can provide targeted pain relief with ease. The drug was embedded within a biocompatible matrix composed of polyhydroxyethyl methacrylate and polyhydroxypropyl methacrylate. The multilayer structure of the dressing, which allows for sustained drug release and an exact application, was achieved through the layer-by-layer coating technique and the inclusion of superparamagnetic iron platinum nanoparticles. The multilayered dressings’ physicochemical, structural, and morphological properties were characterised using various methods. The synergistic effect of the incorporated drug molecules and superparamagnetic nanoparticles on the surface roughness and release kinetics resulted in controlled drug release. In addition, the proposed multilayer wound dressings were found to be biocompatible with human skin fibroblasts. Our findings suggest that the developed wound dressing system can contribute to tailored therapeutic strategies for local pain relief.
Maja Duh, Kristijan Skok, Matjaž Perc, Andrej Markota, and Marko Gosak
Springer Science and Business Media LLC
Marko Gosak, Marko Milojević, Maja Duh, Kristijan Skok, and Matjaž Perc
Elsevier BV
A. Markota, M. Gosak, Maja Duh and Kristijan Skok
MRE Press
Thermoregulation constitutes one of the most important homeostatic systems of the human body. The human thermoregulatory system is highly complex and intertwined with other regulatory homeostatic systems. Different evolutionary adaptations have evolved to ensure a well-regulated body temperature, encompassing simple behavioural (e.g., seeking shelter, going underground) as well as physiological changes (e.g., vasodilatation, sweating). However, when the heat, cold or other stimuli cause a disruption in the thermoregulatory state and our adaptations can no longer cope with the additional stress, the body enters a pathological state. In such instances other measures must be undertaken. In medicine there are several pathological states associated with disruptions in temperature homeostasis. Consequently, these patients have to be, in broad terms, thermoregulated. Speaking specifically, the most common application of thermoregulation is therapeutic temperature management. A prominent example is the utilisation of this technique in post-cardiac arrest patients, who remain comatose after resuscitation. This technique has been in use for almost 20 years since the first major reports on its benefits in improving out-of-hospital cardiac arrest and in-hospital cardiac arrest survival as well as improving neurological outcome. Recently, the findings from one of the biggest targeted temperature international and multicentre trials to date have been published (TTM2 trial; https://ttm2trial.org/). The study surprisingly showed no difference in mortality between patients after out of hospital cardiac arrest, who underwent normo- or hypothermia. Consequently, we might need to re-evaluate certain guidelines, recommendations, and perspectives. The aim of the current review is to present an overview of targeted temperature management in the field of intensive care medicine and cardiac arrest.
Kristijan Skok, Tanja Zidarič, Kristjan Orthaber, Matevž Pristovnik, Nina Kostevšek, Kristina Žužek Žužek Rožman, Sašo Šturm, Lidija Gradišnik, Uroš Maver, and Tina Maver
MDPI AG
Despite medical advances, skin-associated disorders continue to pose a unique challenge to physicians worldwide. Skin cancer is one of the most common forms of cancer, with more than one million new cases reported each year. Currently, surgical excision is its primary treatment; however, this can be impractical or even contradictory in certain situations. An interesting potential alternative could lie in topical treatment solutions. The goal of our study was to develop novel multilayer nanofilms consisting of a combination of polyhydroxyethyl methacrylate (PHEMA), polyhydroxypropyl methacrylate (PHPMA), sodium deoxycholate (NaDOC) with incorporated superparamagnetic iron–platinum nanoparticles (FePt NPs), and the potent anticancer drug (5-fluorouracil), for theranostic skin cancer treatment. All multilayer systems were prepared by spin-coating and characterised by atomic force microscopy, infrared spectroscopy, and contact angle measurement. The magnetic properties of the incorporated FePt NPs were evaluated using magnetisation measurement, while their size was determined using transmission electron microscopy (TEM). Drug release performance was tested in vitro, and formulation safety was evaluated on human-skin-derived fibroblasts. Finally, the efficacy for skin cancer treatment was tested on our own basal-cell carcinoma cell line.
Andrej Markota, Kristijan Skok, Žiga Kalamar, Jure Fluher, and Mario Gorenjak
MDPI AG
The need for temperature modulation (mostly cooling) in critically ill patients is based on the expected benefits associated with decreased metabolic demands. However, evidence-based guidelines for temperature management in a majority of critically ill patients with fever are still lacking. The aim of our retrospective single-site observational study was to determine the differences in ICU treatment between patients in whom their temperature remained within the target temperature range for ≥25% of time (inTT group) and patients in whom their temperature was outside the target temperature range for <24% of time (outTT group). We enrolled 76 patients undergoing invasive mechanical ventilation for respiratory failure associated with sepsis. We observed no significant differences in survival, mechanical ventilation settings and duration, vasopressor support, renal replacement therapy and other parameters of treatment. Patients in the inTT group were significantly more frequently cooled with the esophageal cooling device, received a significantly lower cumulative dose of acetaminophen and significantly more frequently developed a presence of multidrug-resistant pathogens. In our study, achieving a better temperature control was not associated with any improvement in treatment parameters during ICU stay. A lower prevalence of multidrug-resistant pathogens in patients with higher body temperatures opens a question of a pro-pyrexia approach with an aim to achieve better patient outcomes.
Kristijan Skok, Lidija Gradišnik, Helena Čelešnik, Marko Milojević, Uroš Potočnik, Gregor Jezernik, Mario Gorenjak, Monika Sobočan, Iztok Takač, Rajko Kavalar,et al.
MDPI AG
Triple-negative breast cancer (TNBC) is a breast cancer (BC) subtype that accounts for approximately 15–20% of all BC cases. Cancer cell lines (CLs) provide an efficient way to model the disease. We have recently isolated a patient-derived triple-negative BC CL MFUM-BrTNBC-1 and performed a detailed morphological and molecular characterisation and a comprehensive comparison with three commercial BC CLs (MCF-7, MDA-MB-231, MDA-MB-453). Light and fluorescence microscopy were used for morphological studies; immunocytochemical staining for hormone receptor, p53 and Ki67 status; RNA sequencing, qRT-PCR and STR analysis for molecular characterisation; and biomedical image analysis for comparative phenotypical analysis. The patient tissue-derived MFUM-BrTNBC-1 maintained the primary triple-negative receptor status. STR analysis showed a stable and unique STR profile up to the 6th passage. MFUM-BrTNBC-1 expressed EMT transition markers and displayed changes in several cancer-related pathways (MAPK, Wnt and PI3K signalling; nucleotide excision repair; and SWI/SNF chromatin remodelling). Morphologically, MFUM-BrTNBC-1 differed from the commercial TNBC CL MDA-MB-231. The advantages of MFUM-BrTNBC-1 are its isolation from a primary tumour, rather than a metastatic site; good growth characteristics; phenotype identical to primary tissue; complete records of origin; a unique identifier; complete, unique STR profile; quantifiable morphological properties; and genetic stability up to (at least) the 6th passage.
Kristijan Skok, Lidija Gradišnik, Uroš Maver, Nejc Kozar, Monika Sobočan, Iztok Takač, Darja Arko, and Rajko Kavalar
Wiley
Cell lines are widely used for various research purposes including cancer and drug research. Recently, there have been studies that pointed to discrepancies in the literature and usage of cell lines. That is why we have prepared a comprehensive overview of the most common gynaecological cancer cell lines, their literature, a list of currently available cell lines, and new findings compared with the original studies. A literature review was conducted via MEDLINE, PubMed and ScienceDirect for reviews in the last 5 years to identify research and other studies related to gynaecological cancer cell lines. We present an overview of the current literature with reference to the original studies and pointed to certain inconsistencies in the literature. The adherence to culturing rulesets and the international guidelines helps in minimizing replication failure between institutions. Evidence from the latest research suggests that despite certain drawbacks, variations of cancer cell lines can also be useful in regard to a more diverse genomic landscape.
Peter Boor, Philip Eichhorn, Arndt Hartmann, Sigurd F. Lax, Bruno Märkl, Thomas Menter, Kristijan Skok, Julia Slotta-Huspenina, Saskia von Stillfried, Alexandar Tzankov,et al.
Springer Science and Business Media LLC
Sigurd F. Lax, Kristijan Skok, Peter M. Zechner, Lisa Setaffy, Harald H. Kessler, Norbert Kaufmann, Klaus Vander, Natalija Cokić, Urša Maierhofer, Ute Bargfrieder,et al.
Springer Science and Business Media LLC
Zusammenfassung Hintergrund COVID-19 wird als systemische Erkrankung eingestuft. Ein schwerer Verlauf mit tödlichem Ausgang ist möglich und unvorhersehbar. Fragestellung Welche Organsysteme sind primär betroffen? Welche Organveränderungen prädisponieren für einen ungünstigen Verlauf? Welche Organschädigungen finden sich bei letalem Ausgang? Material und Methode Daten aus publizierten Obduktionsstudien (davon 28 eigene publizierte Fälle) in Hinblick auf Organschädigung und mögliche Todesursachen. Ergebnisse Die schwersten Veränderungen finden sich in den Lungen in Form eines diffusen Alveolarschadens als akutes Atemnotsyndrom des Erwachsenen (ARDS), zum Teil bereits mit Fibrose. Thrombosen in kleinen bis mittelgroßen Pulmonalarterien sind mit Lungeninfarkten vergesellschaftet. Häufige Komplikationen sind bakterielle Bronchopneumonien, seltener Pilzpneumonien. Pulmonale Thromboembolien finden sich in 20–30 % der tödlichen Verläufe, auch bei Fehlen einer tiefen Beinvenenthrombose. Eine intestinale Beteiligung von COVID-19 kann mit ischämischer Schädigung des Darmes einhergehen, in erster Linie bedingt durch Schock oder lokale Thrombose. Die Nieren zeigen eine akute Tubulusschädigung als Ausdruck eines akuten Nierenversagens, Lymphknoten und Milz einen Schwund der Lymphozyten, die Nebennierenrinde eine Hyperplasie. In der Leber finden sich häufig eine Steatose, Leberzellnekrosen, ein portales Entzündungsinfiltrat und eine Proliferation der Kupffer-Zellen. Häufige Grunderkrankungen sind in den Autopsiekollektiven arterieller Hypertonus mit hypertensiver und ischämischer Kardiomyopathie und Diabetes mellitus. In großen bevölkerungsbasierten Studien ergibt sich aber für Hypertoniker im Gegensatz zu Diabetikern kein erhöhtes Mortalitätsrisiko. Schlussfolgerungen Pulmonale Kreislaufstörungen mit arteriellen Thrombosen, Infarkten und Pneumonien sind wesentliche und oft letale Komplikationen des ARDS bei COVID-19. Die Erkenntnisse aus Obduktionsstudien haben Therapie und Prophylaxe beeinflusst.
Kristijan Skok, Evelyn Stelzl, Michael Trauner, Harald H. Kessler, and Sigurd F. Lax
Springer Science and Business Media LLC
AbstractThe persistence of SARS-CoV-2 after death of infected individuals is unclear. The aim of this study was to investigate the presence of SARS-CoV-2 RNA in different organs in correlation with tissue damage and post-mortem viral dynamics in COVID-19 deceased. Twenty-eight patients (17 males, 11 females; age 66–96 years; mean 82.9, median 82.5 years) diagnosed with COVID-19 were studied. Swabs were taken post-mortem during autopsy (N = 19) from the throat, both lungs, intestine, gallbladder, and brain or without autopsy (N = 9) only from the throat. Selective amplification of target nucleic acid from the samples was achieved by using primers for ORF1a/b non-structural region and the structural protein envelope E-gene of the virus. The results of 125 post-mortem and 47 ante-mortem swabs were presented as cycle threshold (Ct) values and categorized as strong, moderate, and weak. Viral RNA was detected more frequently in the lungs and throat than in the intestine. Blood, bile, and the brain were negative. Consecutive throat swabs were positive up to 128 h after death without significant increase of Ct values. All lungs showed diffuse alveolar damage, thrombosis, and infarction and less frequently bronchopneumonia irrespective of Ct values. In 30% the intestine revealed focal ischemic changes. Nucleocapsid protein of SARS-CoV-2 was detected by immunohistochemistry in bronchial and intestinal epithelium, bronchial glands, and pneumocytes. In conclusion, viral RNA is still present several days after death, most frequently in the respiratory tract and associated with severe and fatal organ damage. Potential infectivity cannot be ruled out post-mortem.
Kristijan Skok, Jerneja Golub, Damjana Kunej, Andreja Sinkovič, and Andrej Markota
Slovenian Medical Association
Introduction: Application of oxygen at high flows via nasal cannula can be used in patients with hypoxemic respiratory failure and to prevent reintubation. It is well tolerated by the patients and has been associated with lower mortality. However, there is very little data on the use of oxygen at high flows connected to tracheal cannula (HFOTC).
 Case presentation: We present two patients in whom weaning from mechanical ventilation was difficult and we decided to use HFOTC for weaning. Weaning from mechanical ventilation with HFOTC was successful in both patients and they tolerated long term (4 and 2 days, respectively) ventilatory support with HFOTC without adverse effects.
 Conclusions: HFOTC might be used during weaning from mechanical ventilation, however, more data is needed to determine the optimal use of this treatment option.
Sigurd F. Lax, Kristijan Skok, Peter M. Zechner, and Michael Trauner
American College of Physicians
Kristijan Skok, Klaus Vander, Lisa Setaffy, Harald H. Kessler, Stephan Aberle, Ute Bargfrieder, Michael Trauner, and Sigurd F. Lax
Elsevier BV
Sigurd F. Lax, Kristijan Skok, Peter Zechner, Harald H. Kessler, Norbert Kaufmann, Camillo Koelblinger, Klaus Vander, Ute Bargfrieder, and Michael Trauner
American College of Physicians
Background: Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. Objective: To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes. Design: Prospective autopsy study. Setting: Single pathology department. Participants: 11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy). Measurements: Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values. Results: Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts. Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients. Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients. Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis. Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes. Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile. Limitation: The sample was small. Conclusion: COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism. Primary Funding Source: None.
Pavel Skok and Kristijan Skok
Georg Thieme Verlag KG
Abstract Aim The aim of our study was to determine the frequency of patients with “true foreign bodies” in the upper gastrointestinal tract and to evaluate the success of urgent endoscopic procedures in removing these objects. Materials and methods The retrospective study includes patients in which urgent endoscopic investigations of the upper digestive tract were performed in a 23-year period, from 1st January 1994 to 1st January 2018. Results Altogether 13 196 patients were investigated: 5147 (39 %) females and 8049 (61 %) males, mean age 62.8 years, SD ± 18.5 years, range 1–106 years. In only 172 patients – 1.3 % of all subjects – true foreign bodies were detected (in range from 1–8) in the esophagus or stomach. In these patients, a total of 242 endoscopic procedures were performed. In 95.9 % the foreign bodies were removed endoscopically (165/172 patients); in 7 cases (4.1 %) the endoscopic procedures were not successful. Among the foreign bodies removed were various metal or plastic objects: hooks, batteries, coins, keys, screws, razor blades, lighters, buttons, toys, 3 toothbrushes as well as impacted safety pins. In patients with successful endoscopic removal, no significant complications were noted. In 12 patients (12/165, 7.2 %), hemorrhages from the region of the esophagogastric junction or stomach were observed; endoscopic hemostasis was performed in 10/12 patients. Conclusions Urgent endoscopy has proved successful in removing true foreign bodies from the upper gastrointestinal tract in the analyzed period. Different factors affect the success of urgent intervention, the most important being adequate experience, skills, and patience of the endoscopic team.
Kristijan Skok, Uroš Maver, Lidija Gradišnik, Nejc Kozar, Iztok Takač, and Darja Arko
Springer Science and Business Media LLC
Kristijan Skok, Lidija Gradišnik, Helena Čelešnik, Uroš Potočnik, Rajko Kavalar, Iztok Takač, and Uroš Maver
Hindawi Limited
1Faculty of Medicine, Institute of Biomedical Sciences and Department of Pharmacology, University of Maribor, Maribor, Slovenia 2Department of pathology, General Hospital Graz II, Location West, Graz, Austria 3Faculty of Medicine, Center of Human Molecular Genetics and Pharmacogenomics, University of Maribor, Maribor, Slovenia 4Faculty of Chemistry & Chemical Engineering, University of Maribor, Maribor, Slovenia 5Department of Pathology, University Medical Centre Maribor, Maribor, Slovenia 6Faculty of Medicine, Department of Gynaecology and Obstetrics, University of Maribor, Maribor, Slovenia 7Department of Gynaecology and Perinatology, University Medical Centre Maribor, Maribor, Slovenia
Kristijan Skok, Maja Duh, Andraž Stožer, Andrej Markota, and Marko Gosak
Wiley
Thermoregulation plays a vital role in homeostasis. Many species of animals as well as humans have evolved various physiological mechanisms for body temperature control, which are characteristically flexible and enable a fine-tuned spatial and temporal regulation of body temperature in different environmental conditions and circumstances. Human beings normally maintain a core body temperature at around 37°C, and maintenance of this relatively high temperature is critical for survival. Therefore, principles of thermoregulatory control have also important clinical implications. Infections can cause the body temperature to rise internally and several diseases can cause a dysfunction of thermoregulatory mechanisms. Moreover, the utilization of thermotherapies in treating various diseases has been known for thousands of years with a recent resurgence of interest. An increasing amount of research suggests that targeted temperature management is of paramount importance to patient outcomes in certain clinical scenarios. We provide a concise summary of the basic concepts of thermoregulation. Emphasis is given to the principles of thermoregulation in humans in basic pathological states and to targeted temperature management strategies in the clinical environment, with special attention on therapeutic hypothermia in postcardiac arrest patients. Finally, the discussion is focused on the potential offered by computational thermophysiological models for predicting thermal responses of patients in various clinical circumstances, for proposing new perspectives in the design of novel thermal therapies, and to optimize targeted temperature management strategies. This article is categorized under: Cardiovascular Diseases > Cardiovascular Diseases>Computational Models Cardiovascular Diseases > Cardiovascular Diseases>Environmental Factors Cardiovascular Diseases > Cardiovascular Diseases>Biomedical Engineering.
Pavel Skok and Kristijan Skok
Slovenian Medical Association
Človeška črevesna mikrobiota je združba bakterij, arhej, gliv, virusov in parazitov, ki v prebavni cevi tvorijo ekosistem, sestavljen iz približno 1014 mikroorganizmov. Raznolikost te združbe je posledica razlik v genomu gostitelja in vplivu okoljskih dejavnikov, med katere sodijo higiena, prehrana, življenjski slog in uporaba različnih zdravil. Rezultati raziskovalnega dela v zadnjem desetletju so potrdili, da spremenjena sestava mikrobiote (disbioza) prispeva k razvoju različnih bolezni, vključno s srčno-žilnimi, sladkorno boleznijo tipa 2, kronično boleznijo ledvic, nealkoholno zamaščenostjo jeter (NASH), kronično vnetno črevesno boleznijo in celo nekaterimi vrstami raka. V prispevku avtorja predstavita nekaj sodobnih spoznanj o raznoliki sestavi človeške črevesne mikrobiote, diagnostičnih postopkih in nekaterih patofizioloških mehanizmih, ki vplivajo na razvoj srčno-žilnih bolezni.
Sigurd F. Lax, Kristijan Skok, Michael Trauner, and
Springer Science and Business Media LLC
Andrej Markota, Kristijan Skok, Sandra Burja, and Jernej Mori
Mary Ann Liebert Inc
The purpose of our study was to measure surface body temperatures (SBT) and to determine rewarming patterns after surface cooling in adult comatose survivors of cardiac arrest. We performed a prospective study in two phases from April to May 2016 and from December 2017 to March 2018. In the first phase we measured SBT as soon as possible after admission (t0) and 10 minutes later (t10). In the second phase we measured SBT and changes of SBT after local cooling of different regions in the maintenance phase of targeted temperature management. We included six patients to each phase of the study. In the first phase, we observed lower SBT compared with core body temperature (CBT) at t0 and t10, with nonsignificant differences in head and axillary region at t0 (35.2°C ± 1.3°C vs. 36°C ± 0.6°C, p = 0.11, and 35.7°C ± 1.4°C vs. 36°C ± 0.6°C, p = 0.41, respectively) and head at t10 (34.8°C ± 1.6°C vs. 35.9°C ± 0.6°C, p = 0.13). SBT in all other body regions at t0 and t10 was significantly lower compared with CBT (all p values <0.05). In the second phase, SBT was significantly lower compared with CBT in all regions (all p values <0.05). After local cooling we observed no significant differences in rewarming rate between head (2.1 ± 0.3°C/min), thorax (1.6 ± 0.4°C/min), and abdomen (1.7 ± 0.2°C/min), and a significantly faster rewarming rate when comparing other body regions with legs (0.8 ± 0.4°C/min, all p values <0.03). To conclude, in comatose survivors of cardiac arrest we discovered lower SBT compared with CBT, necessitating CBT measurements as soon as possible, and higher SBT and rewarming rates after local cooling in central (head, thorax, and abdomen) compared with peripheral (upper and lower extremities) regions of the body.
Kristijan Skok, Gaja Hladnik, Anja Grm, and Anton Crnjac
MDPI AG
Malignant pleural effusion (MPE) is an exudative effusion with malignant cells. MPE is a common symptom and accompanying manifestation of metastatic disease. It affects up to 15% of all patients with cancer and is the most common in lung, breast cancer, lymphoma, gynecological malignancies and malignant mesothelioma. In the last year, many studies were performed focusing on the pathophysiological mechanisms of MPE. With the advancement in molecular techniques, the importance of tumor-host cell interactions is becoming more apparent. Additionally, the process of pathogenesis is greatly affected by activating mutations of EGFR, KRAS, PIK3CA, BRAF, MET, EML4/ALK and RET, which correlate with an increased incidence of MPE. Considering all these changes, the authors aim to present a literature review of the newest findings, review of the guidelines and pathophysiological novelties in this field. Review of the just recently, after seven years published, practice guidelines, as well as analysis of more than 70 articles from the Pubmed, Medline databases that were almost exclusively published in indexed journals in the last few years, have relevance and contribute to the better understanding of the presented topic. MPE still presents a severe medical condition in patients with advanced malignancy. Recent findings in the field of pathophysiological mechanisms of MPE emphasize the role of molecular factors and mutations in the dynamics of the disease and its prognosis. Treatment guidelines offer a patient-centric approach with the use of new scoring systems, an out of hospital approach and ultrasound. The current guidelines address multiple areas of interest bring novelties in the form of validated prediction tools and can, based on evidence, improve patient outcomes. However, the role of biomarkers in a clinical setting, possible new treatment modalities and certain specific situations still present a challenge for new research.
Kristijan Skok, Nina Skornšek, Marko Hočevar, and Pavel Skok
Slovenian Medical Association
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.