Wartość diagnostyczna CA125, HE4, ROMA oraz modelu regresji logistycznej w diagnistyce guzów miednicy mniejszej – doświadczenia własne

Objectives: The aim of this study was to compare and evaluate the quality of CA125, HE4, logistic regression model based on CA125 and HE4, and ROMA algorithm in preoperational differential diagnostics of the ovarian tumors. Material and methods: To the study 110 patients enrolled. Based on histopatological examination of removed tumors, they were divided into study group (56 cancer patients) and control one (nonmalignant 54 patients). Serum CA125 and HE4 concentrations were measured following a standard procedure. Results: A commonly accepted referential value for CA125 is 35 IU/ml. In our study, this cut-off value yielded very low sensitivity and specificity results (85.2% and 63.6%, respectively). When we adopted HE4 normal value to be 140 pM,the sensitivity and specificity obtained in the investigated population was 68.5% and 94.6%, respectively. When the cut-off value for HE4 was adopted as 74 pM, the sensitivity improved considerably (88.9%), but specificity decreased to 85.7%. In case of CA125 when we adopted Ca125 normal value to be 77 IU/ml, the sensitivity and specificity obtained in the investigated population was 81.5% and 83.6%, respectively. In analysis based on combination of biomarkers, the highest sensitivity was obtained for the logistic regression model based on CA125 and HE4 (89.5%). A little bit lower sensitivity was achieved for HE4 used as a single diagnostic test (88.9%). The highest specificity was observed for ROMA algorithm (94.5%). This means that ROMA algorithm is the best diagnostic tool to differentiate between the malignant and non-malignant ovarian tumors. Conclusions: 1. ROMA algorithm yielded the highest specificity and slightly lower sensitivity in the case of differential diagnosis between malignant and non-malignant ovarian tumors. Therefore, it should become a basic tool in the ovarian tumors diagnosis prior to a surgery. 2. HE4 as a single diagnostic test (based on one marker) was found to be better suited to the ovarian tumor differential diagnosis than CA125 test. 3. Combined test, based on double marker analysis, should be applied and then the risk of the ovarian cancer should be calculated. This approach is more effective than single marker analysis.Cel pracy: Celem niniejszego badania było porównanie i ocena wartości CA125, HE4, modelu regresji logistycznej oraz algorytmu ROMA w przedoperacyjnej diagnostyce różnicowej guzów przydatków. Materiał i metody: Do badania włączono 110 pacjentki, które na podstawie wyniku badania histopatologicznego usuniętych guzów podzielono na grupę badaną (56 pacjentek z nowotworami złośliwymi) i grupę kontrolną (54 pacjentek ze zmianami niezłośliwymi). Oznaczenie osoczowych stężeń CA125 oraz HE4 wykonano zgodnie z standardową procedurą. Wyniki: Powszechnie uznaną wartością graniczną dla CA125 jest 35 IU/ml. W naszym badaniu, przyjęcie tej wartości punktu odcięcia zaowocowało niskimi wartościami czułości i swoistości – odpowiednio 85,2% oraz 63,6%. Wyjściowo uznaliśmy wartość 140 pM jako punkt odcięcia (wartość sugerowana przez producenta). Dla takiego punktu odcięcia, czułość i swoistość osiągnęły odpowiednio wartość 68,5% i 94,6%. Gdy wartość punktu odcięcia dla HE4 została zmieniona na 74 pM, czułość testu wzrosła do 88,9% a swoistość zmniejszyła się do 85.7%. W przypadku CA125 zmiana wartości punktu odcięcia na 77 IU/ml spowodowała spadek czułości do 81,5% przy jednoczesnym wzroście swoistości do 83,6%. W analizach obejmujących jednocześnie obydwa markery (CA 125 i HE4), model oparty na regresji logistycznej osiągnął najwyższą czułość (89,5%). Niewiele mniejszą wartość czułości osiągnął test oparty na oznaczeniu HE4 (88,9%). Natomiast najwyższą wartość swoistości osiągnął algorytm ROMA (94,5%). Oznacza to że algorytm ROMA jest najlepszym narzędziem diagnostycznym w różnicowaniu złośliwych i niezłośliwych guzów jajnika. Wnioski: 1. Algorytm ROMA osiągnął najwyższą wartość swoistości i niewiele niższą wartość czułości jako narzędzie diagnostyczne w różnicowaniu złośliwych od niezłośliwych guzów jajnika. Dlatego powinien zostać podstawowym narzędziem diagnostycznym przed planowanym leczeniem chirurgicznym. 2. HE4 jako pojedynczy test diagnostyczny osiągnął wyższe wartości czułości i swoistości w porównaniu z CA 125. 3. Jednoczesne oznaczanie dwóch markerów (CA 125 i HE4) oraz obliczanie ryzyka wystąpienia nowotworu złośliwego jest zalecanym postępowaniem u pacjentek z guzami przydatków. Analizy oparte na dwóch markerach są bardziej efektywne niż analizy oparte na pojedynczych markerach

The role of artificial nutrition in gynecological cancer therapy

Cancer patients are at risk of developing malnutrition from underlying disease as well as from cancer treatment. Moreover, weight loss is considered as a predictive factor for disease progression and shorter survival time. As many as 10–20% of patients with cancer die from the results of malnutrition, instead of from the cancer itself. In the case of cancer-related malnutrition, it is necessary to quickly implement individualized nutritional support depending on the type and stage of the disease, metabolic changes, the patient’s condition, expected survival and the function of the gastrointestinal tract. Artificial nutrition reduces the side effects of chemotherapy and improves immunity. Perioperatively it reduces the risk of infection, facilitates wound healing and shortens the length of hospitalization, thereby reducing the costs of the treat- ment. Initially, a malnourished patient, without gastrointestinal dysfunction, qualifies for nutritional counseling. When the energy needs cannot be met by normal feeding, nutritional supplements, taken orally, are recommended. The next step is to feed the patient by nasogastric tube or percutaneous endoscopic gastrostomy. Parenteral nutrition, which results in more side effects, is only started when enteral nutrition is insufficient to ensure adequate nutritional status or in cases of gastrointestinal tract obstruction. The benefit of parenteral nutrition is that it especially provides for those patients with gynaecological cancer who have radiation-induced intestinal damage and post-surgical complications such as short bowel syndrome. Palliative nutrition must to relieve hunger and thirst. Nutritional interventions should be individualized and focused on the changing nutrient needs of the patient and should be supported by physical activity. Regular assessment of the nutritional status of the patient should be an inherent element of the oncological treatment.

The role of immunomodulatory preparations in asthma treatment

Asthma remains one of the most prevalent respiratory tract disorders. The disease affects both adults and children and remains the most common cause of respiratory morbidity. Considering its significant impact on patients’ quality of life and the treatment burdened with side effects, a new therapy approaches affecting the clinical course of asthma are needed. Here we describe the current results that have been obtained on using immunomodulatory preparations in asthma. The analysis of previously published studies was conducted by using the PubMed and Scopus databases.             Probiotics, bacterial lysates (BLs) and pidotimod are immunomodulatory compounds affecting both adaptive and innate immunity. The therapy based on probiotics might modulate the intestinal microbiota and regulate the inflammatory response. Bacterial lysates promote immune response by reversing Th1/Th2 unstable balance, which leads to reduction of allergen-induced airway hyperresponsiveness during asthma exacerbations. Pidotimod stimulates PRRs and increases the release of antimicrobial peptides which also leads to the improvement in the rate of respiratory tract infections. Some studies showed the beneficial effect of described preparations in asthma course. Regrettably, findings do not correspond with each other and the data referring to immunomodulatory compounds is still limited, thus there is an urgent need to conduct more, large sample studies.The conclusion we can only draw is that immunomodulatory compounds may offer an alternative approach for symptom reduction and prophylaxis against both infections and exacerbations of asthma

Passing across the blood-brain barrier in glioblastoma multiforme (GBM)

Introduction and purpose: Blood-brain barrier (BBB) consists of  capillary endothelium, in which there are three types of intercellular junctions - adherent, tight and gap junctions.Efficient therapy involves delivering a therapeutic dose of drug into a specific site in the body, and maintaining this dose for adequate time afterwards. The aim of this study is to review current knowledge of new strategies in drug delivery to CNS and the effectiveness of these methods in glioblastoma multiforme (GBM) treatment. This review was performed using the PubMed database. A brief description of the state of knowledge:  Methods for delivering drugs to the brain are divided into invasive and non-invasive. Invasive methods involve temporary disrupting tight intercellular junctions of the vascular endothelial cells and delivering drugs intracerebrally or intraventricularly during neurosurgical procedures. In recent years, there has been a growing interest in the use of nanoparticles as drug carriers to the central nervous system via blood-brain barrier. The usage of nanoparticles implies many advantages, such as non-invasive, low cost, good biodegradability, stability, ability to carry various types of agents, selectivity and ability to control drug release. Conclusions: Limited options in treating brain located tumors, including glioblastoma multiforme, due to difficulties in drug penetration through the BBB engages scientists to search for new treatments. Crossing the BBB using invasive methods based on interruption of cell junctions show promising results, but they are associated with i.a. a high risk of uncontrolled influx of toxins to the CNS or  ion-electrolyte imbalance, which may lead to neuronal dysfunction. Invasive methods can be effective only in tumors, while treatment of diseases such as Alzheimer’s disease is impossible. Recent studies show that nanoparticles would be a great, non-invasive alternative, but they are difficult to use with relatively low permeability through undamaged BBB. In some studies using nanoparticles as nanocarriers  (EDVDox) or SYMPHONY method (combining photothermal therapy with GNS and immunotherapy of checkpoints in a mouse model) against GBM shows positive results. More research is required to confirm the effectiveness and safety of these treatments

Proteomic pattern of cervico-vaginal fluid (CVF) in an ovarian cancer diagnosis — pilot study

Objectives: High grade serous ovarian cancer (HGSC) is the most common type of ovarian cancer and is responsible for about 90% of ovarian cancer deaths. The diagnostic tests currently used do not increase the detection rates for ovarian cancer. There is a great necessity to develop new and non-invasive diagnostic tests for ovarian cancer (OC). Cervico-vaginal fluid (CVF) seems to be a potential and valuable source of biomarkers for genital tract diseases including ovarian cancer. The aim of our pilot study was to undertake a preliminary proteomic analysis of CVF derived from ovarian cancer patients and to compare these with results from a control group.Material and methods: We analysed and compared samples from a group of ovarian cancer patients and a control group of healthy patients. The study used MALDI-TOF coupled with nanoLC and ClinProTools software for MS, MS/MS spectra collection and proteomic analysis.Results: We identified 404 different proteins in the OC group and 417 proteins in the control group. 239 of the proteins were found to be common to both study groups, 165 proteins were unique to the OC subjects, and 178 proteins were unique to the control subjects. We selected three proteins as the OC markers with the greatest potential: cysteine-rich secretory protein 3, fibronectin and Ly6/PLAUR domain-containing protein 3.Conclusions: The proteins we selected seem to possess great potential as markers for the screening and early detection of OC, especially in non-invasive and low-cost diagnostic tests. However, our findings require more advanced and validated proteomic analysis to confirm the suitability of the selected proteins in everyday medical diagnoses

Rola HE4 w różnicowaniu złośliwych i niezłośliwych patologii endometrium

Objectives: The incidence of endometrial cancer is constantly growing. More aggressive types of endometrial cancer as well as the incidence in younger women is being observed. More than 80% of cases is diagnosed in early stages due to early symptoms like abnormal bleeding. The remaining 20% of asymptomatic cases of endometrial cancer as well as the cases of false negative histopathological diagnoses are mostly the incidences of serous endometrial cancer and are a true diagnostic and therapeutic challenge. This was the reason of our study in which we proposed investigation of HE4 levels as a complementary diagnostic method in management and diagnosing of EC. Material and methods: Serum HE4 level was measured in 92 patients with abnormal vaginal bleeding. Based on histhology after curretage the study group was divided into the benign and malignant endometrial pathology groups. Statistical analysis was performed using Mann-Whitney test Results: The difference of serum HE4 level between benign endometrial pathology and cancer was significant (p = 0.000) and the cut-off for identification of patients with endometrial cancer was 58.08 pmol/l. There was a significant difference between G2 and G3 endometrial cancer, and G1 and G3. (p = 0,4 and p = 0,008 respectively) Patients who needed lymphadenectomy had significantly higher HE4 level than those who had no indications for this procedure (p = 0,001). Conclusions: HE4 is a useful biomarker in diagnosing endometrial cancer. HE4 is associated with high grade endometrial cancer. It can also serve as an useful preoperative counseling tool to identify patients, who may require pelvic and paraaortic lymphadenectomy.Obecnie obserwuje się wzrost zapadalności na raka endometrium, w szczególności bardziej agresywnych typów tej choroby oraz jej występowanie u coraz młodszych pacjentek. Wprawdzie więcej niż 80% przypadków jest diagnozowanych we wczesnych stadiach zaawansowania, dzięki wczesnych objawom, takim jak nieprawidłowe krwawienia. Jednak pacjentki bezobjawowe, jak również przypadki fałszywie negatywnych wyników histopatologicznych są wyzwaniem diagnostycznym i terapeutycznym. W niniejszej pracy dokonano analizy wartości białka HE4 jako metody uzupełniającej diagnostykę raka endometrium. Materiał i metody: Stężenie markera w surowicy krwi zostało oznaczone u 92 pacjentek z nieprawidłowymi krwawieniami. Opierając się na wyniku badania histopatologicznego zostały podzielone na grupę z niezłośliwymi i złośliwymi zmianami endometrium. Analiza statystyczna została wykonana za pomocą testu Mann-Withney. Wyniki: Różnica stężenia HE4 między zmianami niezłośliwymi endometrium a rakiem była istotna statystycznie (p = 0,000) i wartość odcięcia wyniosła 58,08 pmol/l. Różnica stężenia HE4 w stopniu złośliwości raka endometrium G2 i G3 była istotna statystycznie jak również między G1 a G3 (p= 0,4 i p = 0,008 odpowiednio). Pacjentki, które wymagały limfadenektomii miały istotnie wyższe stężenia HE4 od tych, które nie wymagały takiego postępowania (p = 0,001). Wnioski: HE4 jest użytecznym biomarkerem raka endometrium. Jest związany z niskim stopniem zróżnicowania nowotworu. HE4 może być użyteczne w identyfikacji pacjentek wymagających okołoaortalnej i miednicznej limfadenektomii

Increase in IL-15 levels in patients with alopecia areata

Introduction and purpose: Alopecia areata (AA) is a condition that causes non-scarring hair loss (often with acute onset). Alopecia areata in the population occurs in 0.1-0.2% of people, with a similar frequency in men and women. Alopecia areata is an example of an autoimmune disease of the hair follicle. Hair loss in alopecia areata is caused by lymphocytic infiltration around the hair follicle and IFN-γ. IgG antibodies against hair follicle cells are also found in people suffering from alopecia areata.  Recent studies have shown a significant increase in IL-15 in AA. The aim of the study was to review the current knowledge on the use of IL-15 in the treatment of alopecia areata.A brief description of the state of knowledge: Interleukin-15 (IL-15) is a pleiotropic cytokine that exhibits multidirectional biological effects on various cell types. It affects the functions of the immune system, both innate and acquired, and therefore plays an important role in inflammation and during the immune response to infections and infestations. In the AA mouse model, antibody-mediated blockade of IFN-γ, interleukin-2 (IL-2), or interleukin-15 receptor β (IL-15Rβ) prevented disease progression by minimizing the accumulation of CD8 (+) NKG2D (+) T cells in the skin and reducing the cutaneous IFN response. The concentration of IL-15 in patients with alopecia areata was significantly higher than in the control group. Moreover, the concentration of IL-15 increased in direct proportion to the area of alopecia, the highest value in patients with total alopecia.For this reason, it is important to search for new medical treatments that will enable patients to stay physically healthy, and what is equally important, to remain mental health. Conclusions: In addition, studies have shown an increase in IL-15 levels in patients with alopecia areata, which correlated with the duration of the disease. However, too few studies conducted so far do not allow conclusions to be drawn regarding the use of IL-15 as a therapeutic point