PURPOSE: Cxbladder tests are urinary biomarker tests for detection of urothelial carcinoma. We developed enhanced Cxbladder tests that incorporate DNA analysis of 6 single nucleotide polymorphisms for the FGFR3 and TERT genes, in addition to the current 5 mRNA biomarkers and clinical risk factors. MATERIALS AND METHODS: Two multicenter, prospective studies were undertaken in: (1) U.S. patients with gross hematuria aged ≥18 years and (2) Singaporean patients with gross hematuria or microhematuria aged >21 years. All patients provided a midstream urine sample and underwent cystoscopy. Samples were retrospectively analyzed using enhanced Cxbladder-Triage (risk stratifies patients), enhanced Cxbladder-Detect (risk stratifies patients and detects positive patients), and the combination enhanced Cxbladder-Triage × Cxbladder-Detect. RESULTS: In the pooled cohort (N=804; gross hematuria: n=484, microhematuria: n=320), enhanced Cxbladder-Detect had a sensitivity of 97% (95% CI 89%-100%), specificity of 90% (95% CI 88%-92%), and negative predictive value of 99.7% (95% CI 99%-100%) for detection of urothelial carcinoma. Overall, 83% of patients were enhanced Cxbladder-Detect-negative (ie, needed no further work-up). Of 133 enhanced Cxbladder-Detect-positive patients, 59 had a confirmed tumor, of which 19 were low-grade noninvasive papillary carcinoma or papillary urothelial neoplasm of low malignant potential. In total, 40 tumors were high-grade Ta, T1-T4, Tis, including concomitant carcinoma in situ. Of the 74 patients with normal cystoscopy, 41 were positive by single nucleotide polymorphism analysis. Enhanced Cxbladder-Triage and enhanced Cxbladder-Detect had significantly better specificity than the first-generation Cxbladder tests (P < .001). CONCLUSIONS: This study in ethnically diverse patients with hematuria showed the analytical validity of the enhanced Cxbladder tests.
- MeSH
- cystoskopie MeSH
- dospělí MeSH
- hematurie etiologie genetika MeSH
- hodnocení rizik MeSH
- karcinom in situ * MeSH
- karcinom z přechodných buněk * diagnóza genetika moč MeSH
- lidé MeSH
- mladiství MeSH
- mutace MeSH
- nádorové biomarkery genetika moč MeSH
- nádory močového měchýře * diagnóza genetika moč MeSH
- prospektivní studie MeSH
- receptor fibroblastových růstových faktorů, typ 3 genetika MeSH
- retrospektivní studie MeSH
- senzitivita a specificita MeSH
- telomerasa * genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Karcinom prsu s pozitivitou HER2 tvoří asi 15 % všech diagnostikovaných prsních karcinomů. Overexprese a amplifikace HER2 je spojena s horší prognózou, ale zároveň je také účinným cílem anti-HER2 léčby. Úplná blokáda signálu pro růst a progresi nádoru zprostředkovaného receptorem HER2 je větší zárukou účinnosti anti-HER2 léčby v různých fázích nemoci.
Breast cancer with HER2 positivity accounts for about 15% of all diagnosed breast cancers. Overexpression and amplification of HER2 is associated with a worse prognosis however, it is also an effective target for anti-HER2 therapy. Complete blockade of the HER2 receptor-mediated signal for tumour growth and progression is a bigger guarantee of the efficacy of anti-HER2 therapy at different stages of the disease.
Nově definovaná kategorie HER2-low karcinomu prsu představuje onemocnění s nízkou expresí receptoru HER2 napříč luminálními a triple negativními subtypy nemoci. K dosud užívaným léčebným možnostem, jakými jsou chemoterapie, cílená léčba a imunoterapie checkpoint inhibitory, jsou nově zaváděny tzv. konjugáty protilátka-léčivo 2. generace, ke kterým patří trastuzumab deruxtekan a sacituzumab govitekan. Následující sdělení se věnuje vymezení pojmu HER2-low karcinom prsu, definici konjugátu protilátka-léčivo a jejich významu pro léčbu HER2-low karcinomu prsu.
The newly defined category of HER2-low breast cancer represents disease with low HER2 receptor expression across luminal and triple negative subtypes of the disease. In addition to previously used treatment options such as chemotherapy, targeted therapy and checkpoint inhibitor immunotherapy, second-generation antibody-drug conjugates, which include trastuzumab deruxtecan and sacituzumab govitecan, are newly introduced. The following review discusses the definition of HER2-low breast cancer, the definition of antibody-drug conjugates and their relevance to the treatment of HER2-low breast cancer.
- MeSH
- biopsie MeSH
- cystosarcoma phyllodes diagnóza patologie terapie MeSH
- fibroadenom diagnóza patologie terapie MeSH
- fibrocystická nemoc prsu diagnóza patologie terapie MeSH
- hamartom diagnóza patologie terapie MeSH
- intraduktální neinfiltrující karcinom diagnóza patologie terapie MeSH
- lidé MeSH
- lipom chirurgie diagnóza patologie MeSH
- mamografie MeSH
- mastodynie etiologie farmakoterapie MeSH
- nádory prsu * diagnóza patologie terapie MeSH
- nemoci prsů MeSH
- papilom intraduktální diagnóza patologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
BACKGROUND: Several randomised, phase 3 trials have investigated the value of different techniques of accelerated partial breast irradiation (APBI) for patients with early breast cancer after breast-conserving surgery compared with whole-breast irradiation. In a phase 3 randomised trial, we evaluated whether APBI using multicatheter brachytherapy is non-inferior compared with whole-breast irradiation. Here, we present the 10-year follow-up results. METHODS: We did a randomised, phase 3, non-inferiority trial at 16 hospitals and medical centres in Austria, Czech Republic, Germany, Hungary, Poland, Spain, and Switzerland. Patients aged 40 years or older with early invasive breast cancer or ductal carcinoma in situ treated with breast-conserving surgery were centrally randomly assigned (1:1) to receive either whole-breast irradiation or APBI using multicatheter brachytherapy. Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with a supplemental boost of 10 Gy to the tumour bed, and APBI was delivered as 30·1 Gy (seven fractions) and 32·0 Gy (eight fractions) of high-dose-rate brachytherapy in 5 days or as 50 Gy of pulsed-dose-rate brachytherapy over 5 treatment days. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was ipsilateral local recurrence, analysed in the as-treated population; the non-inferiority margin for the recurrence rate difference (defined for 5-year results) was 3 percentage points. The trial is registered with ClinicalTrials.gov, NCT00402519; the trial is complete. FINDINGS: Between April 20, 2004, and July 30, 2009, 1328 female patients were randomly assigned to whole breast irradiation (n=673) or APBI (n=655), of whom 551 in the whole-breast irradiation group and 633 in the APBI group were eligible for analysis. At a median follow-up of 10·36 years (IQR 9·12-11·28), the 10-year local recurrence rates were 1·58% (95% CI 0·37 to 2·8) in the whole-breast irradiation group and 3·51% (1·99 to 5·03) in the APBI group. The difference in 10-year rates between the groups was 1·93% (95% CI -0·018 to 3·87; p=0·074). Adverse events were mostly grade 1 and 2, in 234 (60%) of 393 participants in the whole-breast irradiation group and 314 (67%) of 470 participants in the APBI group, at 7·5-year or 10-year follow-up, or both. Patients in the APBI group had a significantly lower incidence of treatment-related grade 3 late side-effects than those in the whole-breast irradiation group (17 [4%] of 393 for whole-breast irradiation vs seven [1%] of 470 for APBI; p=0·021; at 7·5-year or 10-year follow-up, or both). At 10 years, the most common type of grade 3 adverse event in both treatment groups was fibrosis (six [2%] of 313 patients for whole-breast irradiation and three [1%] of 375 patients for APBI, p=0·56). No grade 4 adverse events or treatment-related deaths have been observed. INTERPRETATION: Postoperative APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is a valuable alternative to whole-breast irradiation in terms of treatment efficacy and is associated with fewer late side-effects. FUNDING: German Cancer Aid, Germany.
- MeSH
- brachyterapie * škodlivé účinky MeSH
- intraduktální neinfiltrující karcinom * patologie MeSH
- lidé MeSH
- lokální recidiva nádoru chirurgie MeSH
- nádory prsu * patologie MeSH
- segmentální mastektomie škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Cíl: Epidemiologie a zhodnocení významu chirurgických okrajů v léčbě HSIL vulvy – analýza vlastního souboru. Soubor a metodika: Do studie byly prospektivně zařazovány ženy s nálezem histologicky potvrzené HPV asociované prekancerózy vulvy od 10/2016 do 1/2022. Celkem bylo zařazeno 65 žen. Po chirurgickém ošetření byly ženy podle chirurgického okraje rozděleny do skupin a sledovány v pravidelných intervalech. Výsledky: Sedmnáct žen (26 %) s diagnostikovanou HPV asociovanou prekancerózou vulvy bylo ve věku do 49 let, 48 žen (74 %) bylo ve věku nad 49 let. Recidivy HPV asociovaných prekanceróz byly v excizích s dosahem HSIL do okraje, resp. okrajem do 1 mm vč. a okrajem 1–3 mm diagnostikovány ve 12,3 %, resp. 1,5 % a 3,1 % případů. Riziko recidivy při dosahu léze do okraje je ve srovnání se zdravým okrajem 1–3 mm statisticky významné. Závěr: Při zachování minimálního zdravého okraje (1–3 mm) je riziko recidivy HPV asociovaných prekanceróz vulvy akceptovatelné při současném příznivém kosmetickém efektu a minimalizaci narušení psychosexuální funkcí žen. Nutností jsou dlouhodobé pravidelné kontroly.
Objective: Epidemiology and evaluation of the importance of surgical margins in the treatment of vulvar H-SIL – analysis of own data. Material and methods: The prospective study included women diagnosed with HPV-associated vulvar epithelial neoplasia from 10/2016 to 1/2022. A total of 65 women were included. After surgical treatment, the women were distributed to groups according to surgical margins and were followed-up at regular intervals. Results: Seventeen women (26%) diagnosed with HPV-associated vulvar intraepithelial neoplasia were under 49 years, whereas 48 women (74%) were older than 49 years. Recurrence rates of HPV-associated precancers were 12.3%, 1.5% and 3.1% in excisions with positive margins up to 1 mm peripheral margins and 1–3 mm peripheral margins, respectively. The risk of recurrence when the lesion reaches the margin is statistically significant, compared to a healthy margin of 1–3 mm. Conclusion: Keeping the minimal healthy margin (1–3 mm) seems to be an acceptable risk of recurrence of HPV-associated vulvar intraepithelial neoplasia with positive cosmetic effect and minimal risk of disturbing the psychosexual functions of women. Long-term regular follow-up is necessary.
CONTEXT: The European Association of Urology (EAU) has released an updated version of the guidelines on non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To present the 2021 EAU guidelines on NMIBC. EVIDENCE ACQUISITION: A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines since the 2020 version was performed. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. EVIDENCE SYNTHESIS: Tumours staged as Ta, T1 and carcinoma in situ (CIS) are grouped under the heading of NMIBC. Diagnosis depends on cystoscopy and histological evaluation of tissue obtained via transurethral resection of the bladder (TURB) for papillary tumours or via multiple bladder biopsies for CIS. For papillary lesions, a complete TURB is essential for the patient's prognosis and correct diagnosis. In cases for which the initial resection is incomplete, there is no muscle in the specimen, or a T1 tumour is detected, a second TURB should be performed within 2-6 wk. The risk of progression may be estimated for individual patients using the 2021 EAU scoring model. On the basis of their individual risk of progression, patients are stratified as having low, intermediate, high, or very high risk, which is pivotal to recommending adjuvant treatment. For patients with tumours presumed to be at low risk and for small papillary recurrences detected more than 1 yr after a previous TURB, one immediate chemotherapy instillation is recommended. Patients with an intermediate-risk tumour should receive 1 yr of full-dose intravesical bacillus Calmette-Guérin (BCG) immunotherapy or instillations of chemotherapy for a maximum of 1 yr. For patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. For patients at very high risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is also recommended for BCG-unresponsive tumours. The extended version of the guidelines is available on the EAU website at https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/. CONCLUSIONS: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. PATIENT SUMMARY: The European Association of Urology has released updated guidelines on the classification, risk factors, diagnosis, prognostic factors, and treatment of non-muscle-invasive bladder cancer. The recommendations are based on the literature up to 2020, with emphasis on the highest level of evidence. Classification of patients as having low, intermediate, or and high risk is essential in deciding on suitable treatment. Surgical removal of the bladder should be considered for tumours that do not respond to bacillus Calmette-Guérin (BCG) treatment and tumours with the highest risk of progression.
- MeSH
- aplikace intravezikální MeSH
- BCG vakcína terapeutické užití MeSH
- invazivní růst nádoru MeSH
- karcinom in situ * diagnóza terapie MeSH
- lidé MeSH
- nádory močového měchýře * diagnóza patologie terapie MeSH
- urologie * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE OF REVIEW: The most common prostatic cancers (PCa) are acinary adenocarcinomas. Histological subtypes have been variably defined. The purpose of this review is to discuss unusual histological patterns and subtypes of acinar adenocarcinoma, as well as other types of PCa and their prognostic and therapeutic relevance. RECENT FINDINGS: The new term 'subtype' for morphologically defined tumor entities replaced the term 'variant' in the new 2022 classification of the WHO to allow for clear terminological distinction from genetic variants. The 2022 WHO classification mentions prostatic intraepithelial neoplasia (PIN)-like carcinoma, signet-cell-like adenocarcinoma, sarcomatoid carcinoma and pleomorphic-giant-cell adenocarcinoma of the prostate as true subtypes of acinary PCa. Other forms of acinary PCa are termed unusual histological patterns and include atrophic, foamy-cell, microcystic, pseudohyperplastic and mucinous patterns. Nonacinar forms of prostate cancer include other glandular PCa, the ductal adenocarcinoma and the treatment-associated neuroendocrine carcinoma, and nonglandular PCa, the adenosquamous carcinoma, the squamous cell carcinoma and the adenoid cystic (basal cell) carcinoma of the prostate. SUMMARY: True subtypes of acinary PCa and other forms of glandular and nonglandular PCa show relevant differences in prognosis and treatment approach compared with classic acinary PCa. The relevance of unusual histological patterns mainly lies in their deceptive benign appearance and the need for pathologists to know about these entities for accurate and timely diagnosis.
- MeSH
- adenokarcinom * patologie MeSH
- lidé MeSH
- nádory prostaty * patologie terapie MeSH
- prostata patologie MeSH
- prostatická intraepiteliální neoplazie * patologie MeSH
- spinocelulární karcinom * patologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE OF REVIEW: This review aims to analyze the current place of active surveillance (AS) in non-muscle-invasive bladder cancer (NMIBC). RECENT FINDINGS: A growing body of evidence suggests that AS protocols for pTa low-grade (TaLG) NMIBC are safe and feasible. However, current guidelines have not implemented AS due to a lack of high-quality data. Available studies included pTa tumors, with only one study excluding pT1-NMIBC. Inclusion/exclusion criteria were heterogeneously defined based on tumor volume, number of tumors, carcinoma in situ (CIS), or high-grade (HG) NMIBC. Tumor volume <10 mm and <5 lesions were used as cut-offs. Positive urinary cytology (UC) or cancer-related symptoms precluded inclusion. Surveillance within the first year consisted of quarterly cystoscopy. AS stopped upon the presence of cancer-related symptoms, change in tumor morphology, positive UC, or patient's request. With a median time on AS of 16 months, two-thirds of the patients failed AS. Progression to muscle-invasive bladder cancer (MIBC) was rare and occurred only in patients with pT1-NIMBC at inclusion. SUMMARY: AS in NMIBC is an attractive concept in the era of personalized medicine, but strong evidence is still awaited. A more precise definition of patient inclusion, follow-up, and failure criteria is required to improve its implementation in daily clinical practice.
- MeSH
- hlava patologie MeSH
- intraduktální neinfiltrující karcinom * patologie MeSH
- lidé MeSH
- nádory podčelistní slinné žlázy * diagnóza patologie MeSH
- podčelistní slinná žláza diagnostické zobrazování patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
