Klinični pomen določanja mRNA tumorskih označevalcev v urinu pri bolnikih z rakom sečnega mehurja

Pogorevc, Diana (avtor), Osredkar, Joško (mentor)

Rak sečnega mehurja (RSM) v Evropi predstavlja 6,2 % vseh rakov pri moških in 1,6 % pri ženskah. V treh četrtinah primerov ga odkrijemo v začetni, površinski stopnji, ki lahko sčasoma napreduje v mišično invazivni rak, ta pa povzroča hude zdravstvene težave in lahko vodi tudi v smrt bolnika. Glavno načelo zdravljenja površinskega RSM je takojšnja transuretralna resekcija tumorja in pogosto spremljanje s cistoskopskimi pregledi, ki so invazivni, boleči in imajo nevarnost hujših zapletov. V zadnjem desetletju so odkrili številne tumorske označevalce, ki so prisotni v urinu in bi teoretično lahko nadomestili cistoskopsko spremljanje ali vsaj omogočili daljše časovne razmike med cistoskopskimi pregledi. Eden izmed testov, ki temelji na teh označevalcih je Cepheid Xpert Bladder Cancer test, ki do naše raziskave v Sloveniji še ni bil klinično uporabljen. Namen magistrske naloge je bil ovrednotiti klinični pomen Cepheid Xpert Bladder Cancer testa za odkrivanje in spremljanje raka mehurja. V raziskavo smo vključili 54 bolnikov, od tega 42 moških in 12 žensk. Vsi so že imeli potrjeno diagnozo RSM. Med njimi so bili bolniki z novo odkritim RSM in so bili hospitalizirani na Kliničnem oddelku za urologijo UKC Ljubljana pred prvo transuretralno resekcijo RSM in bolniki, ki so prišli na redno kontrolno cistoskopijo v cistoskopirnico Kliničnega oddelka za urologijo UKC Ljubljana po predhodni transuretralni resekciji RSM. Rezultati naše študije so pokazali, da je občutljivost Xpert BC Monitor testa za napovedovanje pozitivnega in sumljivega rezultata cistoskopije bistveno večja kot pri citološkem pregledu urina (75,0 % v primerjavi z 41,2 %), boljša je tudi negativna napovedna vrednost (93,0 % v primerjavi z 85,4 %). Visoka diskriminantna moč Xpert BC Monitor testa med malignimi in benignimi histološkimi skupinami je posledica zelo signifikantne razlike med mediano skupne vrednosti LDA v obeh skupinah (0,2486 za benigno in 0,9869 za maligno skupino). Skupna občutljivost in negativna napovedna vrednost Xpert BC Monitor testa za napovedovanje malignega histološkega rezultata znašata 76,9 % in 93,0 % in močno presegata vrednosti citološkega pregleda urina (46,2 % in 85,4 %). Na podlagi dobljenih rezultatov lahko podamo naslednje ugotovitve: Xpert BC Monitor test je pokazal bistveno večjo občutljivost in negativno napovedno vrednost v primerjavi s citološkim pregledom urina. Njegova sposobnost odkrivanja ponovitve tumorjev bi lahko spremenila nadaljnje urnike kontrolnih cistoskopij. Pri bolnikih z negativnim rezultatom Xpert BC Monitor testa bi lahko povečali priporočene intervale med posameznimi cistoskopijami. Xpert BC Monitor test je dovolj dober in zanesljiv, da kombiniranje le-tega s citopatološkim pregledom urina ne izboljša njegove zmogljivosti.

• Jezik: Slovenski jezik
• Ključne besede: rak sečnega mehurja, mRNA tumorski označevalci, test Cepheid Xpert Bladder Cancer Monitor, cistoskopija, citopatološka preiskava urina
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2021
• PID: 20.500.12556/RUL-125349
• Datum objave v RUL: 12.03.2021

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Clinical significance of tumor markers mRNAs in urine of bladder cancer patients

Izvleček

Bladder cancer (BC) in Europe accounts for 6,2 % of all cancers in men and 1,6 % in women. In three-quarters of cases, it is detected in the initial, superficial stage, which can eventually progress to muscle-invasive cancer, which in turn causes severe health problems and can even lead to the death of the patient. The main principle of treatment of superficial BC is immediate transurethral resection of the tumor and frequent monitoring with cystoscopic examinations, which are invasive, painful and have a risk of severe complications. Over the last decade, several tumor markers have been discovered that are present in urine and could theoretically replace cystoscopic monitoring or at least allow longer intervals between cystoscopic examinations. One of the tests based on these markers is the Cepheid Xpert Bladder Cancer test, which has not been used clinically in Slovenia until our research. The purpose of the master's thesis was to evaluate the clinical significance of the Cepheid Xpert Bladder Cancer test for the detection and monitoring of bladder cancer. We included 54 patients in the study, of which 42 were men and 12 were women. All already had a confirmed diagnosis of BC. Among them were patients with newly discovered BC and were hospitalized at the Clinical Department of Urology at the University Medical Center Ljubljana before the first transurethral resection of the BC and patients who came for regular control cystoscopy in the cystoscopy room of the Clinical Department of Urology at the University Medical Center Ljubljana after previous transurethral resection. The results of our study showed that the sensitivity of the Xpert BC Monitor test to predict a positive and suspicious cystoscopy result is significantly higher than in the cytological examination of urine (75,0 % compared to 41,2 %), the negative prognostic value is also better (93,0 % compared to 85,4 %). The high discriminant power of the Xpert BC Monitor test between malignant and benign histological groups is due to an incredibly significant difference between the median total LDA values in both groups (0,2486 for the benign and 0,9869 for the malignant group). The overall sensitivity and negative predictive value of the Xpert BC Monitor test for predicting malignant histological outcome are 76,9 % and 93,0 %, respectively, and greatly exceed the values of urine cytological examination (46,2 % and 85,4 %). Based on the obtained results, we can make the following conclusions: Xpert BC Monitor test showed significantly higher sensitivity and negative prognostic value compared to cytological examination of urine. Its ability to detect tumor recurrence could alter further cystoscopy follow-up schedules. In patients with a negative Xpert BC Monitor test result, the recommended intervals between individual cystoscopies could be increased. The combination of both tests, the Xpert BC Monitor test and the cytological examination of the urine, does not improve the performance of the Xpert BC Monitor test itself.

• Ključne besede: bladder cancer, mRNA tumor markers, Cepheid Xpert Bladder Cancer Monitor test, cystoscopy, cytopathological examination of urine