1. Unravelling the lung cancer diagnostic pathway : identifying gaps and opportunities for improvementMateja Marc-Malovrh, Katja Adamič, 2024, izvirni znanstveni članek Povzetek: Background
A fast and well-organized complex diagnostic process is important for better success in the treatment of lung cancer patients. The aim of our study was to reveal the gaps and inefficiencies in the diagnostic process and to suggest improvement strategies in a single tertiary centre in Slovenia.
Patients and methods
We employed a comprehensive approach to carefully dissect all the steps in the diagnostic journey for individuals suspected of having lung cancer. We gathered and analysed information from employees and patients involved in the process by dedicated questionnaires. Further, we analysed the patients’ data and calculated the diagnostic intervals for patients in two different periods.
Results
The major concerns among employees were stress and excessive administrative work. The important result of the visual journey and staff reports was the design of electronic diagnostic clinical pathway (eDCP), which could substantially increase safety and efficacy by diminishing the administrative burden of the employees. The patients were generally highly satisfied with diagnostic journey, but reported too long waiting times. By analysing two time periods, we revealed that diagnostic intervals exceeded the recommended timelines and got importantly shorter after two interventions - strengthening the diagnostic team and specially by purchase of additional PET-CT machine (the average time from general practitioner (GP) referral to the multidisciplinary treatment board (MDTB) decision was 50.8 [± 3.0] prior and 37.1 [± 2.3] days after the interventions).
Conclusions
The study illuminated opportunities for refining the diagnostic journey for lung cancer patients, underscoring the importance of both administrative and capacity-related enhancements. Ključne besede: lung cancer, diagnostic pathway, improvement Objavljeno v DiRROS: 02.06.2025; Ogledov: 126; Prenosov: 77
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2. Risk of cancer after primary total hip replacement : the influence of bearings, cementation and the material of the stemVesna Levašič, Ingrid Milošev, Vesna Zadnik, 2018, izvirni znanstveni članek Povzetek: Background and purpose - Despite the increasing number of total hip replacements (THRs), their systemic influence is still not known. We have studied the influence of specific features of THRs-the bearing surface, the use of bone cement and the material of the stem-on the cancer incidence. Patients and methods - In a retrospective cohort study we identified 8,343 patients with THRs performed at Valdoltra Hospital from September 1, 1997 to December 31, 2009. Patient data were linked to national cancer and population registries. The standardized incidence ratios (SIR) and Poisson regression relative risks (RR) were calculated for all and specific cancers. Results - General cancer risk in our cohort was comparable to the population risk. Comparing with population, the risk of prostate cancer was statistically significantly higher in patients with metal-on-metal bearings (SIR =1.35); with metal-on-polyethylene bearings (SIR =1.30), with non-cemented THRs (SIR =1.40), and with titanium alloy THRs (SIR =1.41). In these last 3 groups there was a lower risk of hematopoietic tumors (SIR =0.69; 0.66 and 0.66 respectively). Risk of kidney cancer was significantly higher in the non-metal-on-metal, non-cemented, and titanium alloy groups (SIR =1.30; 1.46 and 1.41 respectively). Risk of colorectal and lung cancer was significantly lower in the investigated cohort (SIR =0.82 and 0.83, respectively). Risk for all cancers combined as well as for prostate and skin cancer, shown by Poisson analysis, was higher in the metal-on-metal group compared with non-metal-on-metal group (RR =1.56; 2.02 and 1.92, respectively). Interpretation - Some associations were found between the THRs' features, especially a positive association between metal-on-metal bearings, and specific cancers. Ključne besede: oncology, cancer registry, replacements, materials Objavljeno v DiRROS: 19.05.2025; Ogledov: 179; Prenosov: 87
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4. Gut microbiome in cancer : the next big opportunity for better patient outcomes?Jure Povšin, Timotej Sotošek, Metka Novak, Barbara Breznik, 2025, pregledni znanstveni članek Povzetek: The gut microbiome, a diverse community of microorganisms in the human body, plays an important role in maintaining health and influences various processes such as digestion, immunity, and protection against pathogens. A person's unique gut microbiome, shaped by factors such as birth method, diet, antibiotics, and lifestyle, contributes to bodily functions such as nutrient metabolism, drug processing, and im-mune regulation. Changes in the gut microbiome are associated with a predisposition to cancer and can influence the effectiveness of cancer treatments. Dysbiosis in the gut microbiome can lead to inflammation, tumor development, and metastasis, highlight-ing its importance in cancer research and prevention. The gut microbiota significantly influences cancer development and treatment outcomes. Certain bacteria enhance the effects of therapies such as cyclophosphamide and contribute to the body's im-mune response against tumors. Microbes produce anti-cancer molecules and probiotic compounds, making them potential tools in cancer prevention and treatment. Future research aims to develop targeted antibiotics and explore fecal microbiota transfer to selectively manipulate the microbiota for improved cancer treatment. Due to genetic and physiological similarities, mouse models are invaluable in biomedical research. However, because the gut microbiome of humans and mice and the composition of the tumor microenvironment differ, direct comparison between these two models can be challenging in research. Bridging these gaps is crucial for comparative medicine, especially in cancer research where the microbiome plays an important role in treat-ment outcomes. One important area where the gut microbiome could offer potential new treatment options is in primary brain tumors such as gliomas. To date, there are no long-lasting effective treatments for this type of cancer, but research in mouse models shows a link between tumor progression and response to treatment with changes in the gut microbiome. Overall, the gut microbiome and its modulation represent an opportu-nity for more efficient future cancer treatment. Ključne besede: gut microbiome, cancer, treatment outcome, tumor models, glioma Objavljeno v DiRROS: 03.04.2025; Ogledov: 362; Prenosov: 151
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5. Prospective observational study of COVID-19 vaccination in patients with thoracic malignancies : adverse events, breakthrough infections and survival outcomesUrška Janžič, Andrej Janžič, Abed Agbarya, Urška Bidovec, Katja Mohorčič, Marina Čakš, Peter Korošec, Matija Rijavec, Erik Škof, 2024, izvirni znanstveni članek Povzetek: Abstract: Due to the devastating COVID-19 pandemic, a preventive tool in the form of vaccination was introduced. Thoracic cancer patients had one of the highest rates of morbidity and mortality due to COVID-19 disease, but the lack of data about the safety and effectiveness of vaccines in this population triggered studies like ours to explore these parameters in a cancer population. Out of 98 patients with thoracic malignancies vaccinated per protocol, 60–75% experienced some adverse events (AE) after their first or second vaccination, most of them were mild and did not interfere with their daily activities. Out of 17 severe AEs reported, all but one were resolved shortly after vaccination. No significant differences were noted considering AE occurrence between different cancer therapies received after the first or second vaccination dose, p = 0.767 and p = 0.441, respectively. There were 37 breakthrough infections either after the first (1), second (13) or third (23) vaccine dose. One patient died as a direct consequence of COVID-19 infection and respiratory failure, and another after disease progression with simultaneous severe infection. Eight patients had moderate disease courses, received antiviral therapies and survived without consequences. Vaccination did not affect the time to disease progression or death from underlying cancer. Ključne besede: thoracic malignancies, cancer therapy, COVID-19 vaccination, adverse events, breakthrough infection Objavljeno v DiRROS: 24.03.2025; Ogledov: 286; Prenosov: 150
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6. An international comparability study on quantification of mRNA gene expression ratios: CCQM-P103.1Alison S. Devonshire, Tina Demšar, Jana Žel, Andrej Blejec, Mojca Milavec, 2016, izvirni znanstveni članek Povzetek: Measurement of RNA can be used to study and monitor a range of infectious and non-communicable diseases, with profiling of multiple gene expression mRNA transcripts being increasingly applied to cancer stratification and prognosis. An international comparison study (Consultative Committee for Amount of Substance (CCQM)-P103.1) was performed in order to evaluate the comparability of measurements of RNA copy number ratio for multiple gene targets between two samples. Six exogenous synthetic targets comprising of External RNA Control Consortium (ERCC) standards were measured alongside transcripts for three endogenous gene targets present in the background of human cell line RNA. The study was carried out under the auspices of the Nucleic Acids (formerly Bioanalysis) Working Group of the CCQM. It was coordinated by LGC (United Kingdom) with the support of National Institute of Standards and Technology (USA) and results were submitted from thirteen National Metrology Institutes and Designated Institutes. The majority of laboratories performed RNA measurements using RT-qPCR, with datasets also being submitted by two laboratories based on reverse transcription digital polymerase chain reaction and one laboratory using a next-generation sequencing method. In RT-qPCR analysis, the RNA copy number ratios between the two samples were quantified using either a standard curve or a relative quantification approach. In general, good agreement was observed between the reported results of ERCC RNA copy number ratio measurements. Measurements of the RNA copy number ratios for endogenous genes between the two samples were also consistent between the majority of laboratories. Some differences in the reported values and confidence intervals (‘measurement uncertainties’) were noted which may be attributable to choice of measurement method or quantification approach. This highlights the need for standardised practices for the calculation of fold change ratios and uncertainties in the area of gene expression profiling.
Ključne besede: RNA copy number ratio, RT-qPCR, gene expression, normalisation, standardisation, molecular diagnostic, transcriptomics, cancer, diagnostics, biomarker identification and validation Objavljeno v DiRROS: 04.03.2025; Ogledov: 237; Prenosov: 112
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8. Solitary ovarian cancer cells in the peritoneum : what happens below the surface?Laura M.C. Vos, Willemien J. van Driel, Gabe S. Sonke, Juliette O. A. M. van Baal, Koen K. van de Vijver, Cornelis J. F. van Noorden, Christianne A. R. Lok, 2022, izvirni znanstveni članek Povzetek: Background
In advanced epithelial ovarian cancer (EOC), the peritoneum is the primary site of disease recurrence which occurs in >75% of patients despite complete cytoreductive surgery (CRS) and chemotherapy. Macroscopically undetectable remaining cancer cells are deemed to be a source for recurrent disease. We investigated characteristics of occult disease in biopsies of macroscopically normal peritoneum during CRS.
Materials and methods
We included 14 patients with advanced stage high grade serous ovarian cancer (HGSOC). Eleven patients had received neoadjuvant chemotherapy (NACT) and three patients were chemotherapy naïve. Each patient underwent three study-related peritoneal biopsies: 1) of a metastasis, 2) adjacent to a metastasis and 3) at distance from metastases. Cryostat sections were immunohistochemically stained for PAX8 and PanCK as markers of EOC cells and for CD31 as a marker for vascular and lymphatic endothelium. The sections were analyzed semi-quantitatively.
Results
Macroscopically normal peritoneum showed solitary PAX8-positive cells adjacent to and at distance from metastases in all patients. Thirteen percent of these PAX8-positive cells were found to be attached to the mesothelium and are presumably spread through intra-abdominal fluid. Eighty-seven percent of the solitary PAX8-positive cells were found in the stroma underneath the mesothelium, of which 59% were firmly attached to endothelium and 33% were found in the stroma. In most cases, no sign of proliferation of the solitary cells was observed. Only a few clusters of PAX8-positive cells were found. Chemotherapy did not affect these results.
Conclusions
Solitary PAX8-positive cells are present in the macroscopically healthy-looking peritoneum of all EOC patients investigated, irrespective of the distance to macroscopically-visible metastases and of previous treatment. The majority of these solitary cancer cells were attached to endothelium of capillaries, venules or lymphatic vessels. Their solitary character and lack of proliferation suggests a dormant state, which could explain why these cells are unaffected by neo-adjuvant chemotherapy. Ključne besede: ovarian cancer, peritoneal metastasis, translational medical research, human pathology, PAX8, cancer recurrence Objavljeno v DiRROS: 26.02.2025; Ogledov: 257; Prenosov: 166
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