Cíl: Přehled změn v nové verzi stagingové klasifikace FIGO 2023 pro karcinomy endometria. Metodika a výsledky: Nový stagingový systém karcinomu endometria FIGO 2023 přináší klíčové aktualizace pro diagnostiku a léčbu karcinomů endometria. Důležitým krokem v diagnostice je molekulární klasifikace, která umožňuje přesněji stratifikovat riziko recidivy a určit cílené léčebné postupy. Nový stagingový systém vycházející z doporučení mezinárodních společností ESGO, ESTRO a ESP zapracoval kromě popisu patologicko-anatomického rozsahu onemocnění také histopatologické charakteristiky nádoru, mezi které patří histologický typ nádoru a přítomnost lymfangioinvaze. Navíc stagingový systém používá molekulární testování, podle něhož lze rozdělit karcinomy endometria do čtyř prognostických skupin: POLEmut, MMRd, NSMP a p53abn. Každá skupina má své specifické charakteristiky a prognózu. Nejvýznamnější změny nastaly ve stadiích I a II, ve kterých rozdělení na podstadia lépe reflektuje biologické chování nádoru. Tato aktualizace zvyšuje přesnost prognózy a zlepšuje možnosti individualizované léčby pro pacientky s karcinomem endometria. Závěr: Aktualizovaný FIGO staging karcinomu endometria pro rok 2023 zahrnuje různé histologické typy, nádorové rysy a molekulární klasifikaci, aby lépe odrážel současné lepší pochopení komplexní povahy několika typů karcinomu endometria a jejich základního biologického chování. Cílem nového stagingového systému karcinomu endometria je lépe definovat stadia s podobnou prognózou, což umožní přesnější indikaci individualizované adjuvantní radiační nebo systémové léčby včetně využití imunoterapie.
Aim: To review the changes in the new version of the FIGO 2023 staging system for endometrial cancer. Methods and results: The new FIGO 2023 endometrial cancer staging system provides key updates for the diagnosis and treatment of endometrial cancer. An important step in diagnosis is molecular classification, which allows more accurate risk stratification for recurrence and the identification of targeted therapies. The new staging system, based on the recommendations of the international societies ESGO, ESTRO and ESP, incorporates not only the description of the pathological and anatomical extent of the disease, but also the histopathological characteristics of the tumour, including the histological type and the presence of lymphovascular space invasion. In addition, the staging system uses molecular testing to classify endometrial cancers into four prognostic groups: POLEmut, MMRd, NSMP and p53abn. Each group has its own specific characteristics and prognosis. The most significant changes have occurred in stages I and II, in which the sub-staging better reflects the biological behaviour of the tumour. This update increases the accuracy of prognosis and improves individualized treatment options for patients with endometrial cancer. Conclusion: The updated FIGO staging of endometrial cancer for 2023 incorporates different histologic types, tumour features, and molecular classifications to better reflect the current improved understanding of the complex nature of several endometrial cancer types and their underlying bio logic behaviour. The aim of the new endometrial cancer staging system is to better define stages with similar prognosis, allowing for more precise indication of individualised adjuvant radiation or systemic treatment, including the use of immunotherapy.
Cíl: Cílem práce je zhodnotit, jak často dochází ke změně předoperačního a pooperačního stagingu u pacientek s karcinomem endometria. Soubor a metody: Prospektivně jsme hodnotili soubor 166 pacientek s karcinomem endometria. Všechny podstoupily abdominální hysterektomii s bilaterální adnexektomií a detekcí sentinelové uzliny pomocí Tc99m koloidu a patentové modři. U pacientek s vysokým rizikem byla provedena ještě pánevní lymfadenektomie. Analyzovali jsme výsledky předoperačních a pooperačních histologických vyšetření a statisticky je vyhodnotili. Výsledky: Alespoň jedna sentinelová uzlina byla detekována v 71,1 % případů. Ve 40,6 % případů byla detekována sentinelová uzlina oboustranně. Ke změně gradu tumoru v definitivním histologickém vyšetření došlo ve 48 případech (31,4 %). Ke zvýšení gradu tumoru došlo ve 22 případech (14,4 %) a ke snížení gradu tumoru ve 26 případech (17 %). Upgrade tumoru z histologicky low-risk do high-risk skupiny byl v osmi případech. Histopatologický typ tumoru byl v definitivním histologickém vyšetření změněn v 6,6 %, celkem 4,6 % se přesunulo do histopatologicky high-risk skupiny. Lokální stage tumoru se předoperačně a pooperačně lišil v 57,3 %, v 19,2 % se případy přesunuly z low/intermediate-risk skupiny do intermediate-high/high-risk skupiny onemocnění. Závěr: Určení předoperačního stage a grade tumoru je zatíženo velkou chybovostí, mnoho případů je po chirurgickém stagingu přesunuto do intermediate-high/high-risk skupiny onemocnění. Výsledky potvrzují význam druhého čtení histopatologie z předoperačních biopsií u žen referovaných do onkogynekologického centra. Detekce a vyšetření sentinelové uzliny by měly být provedeny i u předoperačně low/intermediate-risk skupin pacientek. Umožní to optimalizaci pooperační léčby.
Objective: The aim of this study was to determine how often changes the stage of the tumour in definitive histology against preoperative clinical stage in patient cohort with diagnosed endometrial cancer. Methods: We evaluated prospectively a cohort of 166 patients with endometrial cancer. They all underwent abdominal hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node biopsy. Patients with high-risk tumours also pelvic lymfadenectomy. We collected data of preoperative diagnostic biopsy and postoperative definitive histology. The data were statistically processed. Results: Detection of sentinel lymph node was successful in 71.1%, bilateral successful detection was in 40.6%. Discrepancy of tumour grade between preoperative biopsy and definitive histology was generally 31.4%. Upgrading of the tumour was in 22 (14.4%) cases, downgrading in 26 (17%) cases. Upgrade from low-risk to high-risk group of tumours was noticed in eight cases. Histopathological tumour type changed in 6.6%, 4.6% moved to histopathologic high-risk group. The tumour stage changed in definite histology in 57.3%, in 19.2% of cases moved from stage low/intermediate-risk group to intermediate-high/high-risk disease group. Conclusion: Correct assessment of preoperative clinical stage and histological grade of endometrial cancer is burdened with a high inaccuracy rate. A lot of cases is up-staged after surgical staging and moved to intermediate-high/high-risk disease group. Results confirm the importance of oncogynaecologic centre II. evaluation of histopathology findings from diagnostic biopsies made in referring hospitals. Sentinel lymph node biopsy should be performed even in clinically low/intermediate-risk disease group.
The profile of the antitumor immune response is an important factor determining patient clinical outcome. However, the influence of the tissue contexture on the composition of the tumor microenvironments of virally induced tumors is not clearly understood. Therefore, we analyzed the immune landscape of two HPV-associated malignancies: oropharyngeal squamous cell carcinoma (OPSCC) and squamous cell carcinoma of uterine cervix (CESC). We employed multiplex immunohistochemistry and immunofluorescence to evaluate the density and spatial distribution of immune cells in retrospective cohorts of OPSCC and CESC patients. This approach was complemented by transcriptomic analysis of purified primary tumor cells and in silico analysis of publicly available RNA sequencing data. Transcriptomic analysis showed similar immune profiles in OPSCC and CESC samples. Interestingly, immunostaining of OPSCC tissues revealed high densities of immune cells in both tumor stroma and tumor epithelium, whereas CESC samples were mainly characterized by the lack of immune cells in the tumor epithelium. However, in contrast to other immune cell populations, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were abundant in both segments of CESC samples and CESC-derived tumor cells expressed markedly higher levels of the PMN-MDSC chemoattractants CXCL1, CXCL5, and CXCL6 than OPSCC tumor cells. Taken together, despite their having the same etiologic agent, the immune infiltration pattern significantly differs between OPSCC and CESC, with a noticeable shift toward prominent MDSC infiltration in the latter. Our data thus present a rationale for a diverse approach to targeted therapy in patients with HPV-associated tumors of different tissue origins.
- Publikační typ
- časopisecké články MeSH
Cíl: Přehled současných znalostí o účinnosti vakcinace proti lidskému papilomaviru (HPV – human papillomavirus) v prevenci recidiv těžké cervikální léze po excizní chirurgické léčbě. Metodika a výsledky: HPV infekce je nezbytná pro rozvoj většiny cervikálních prekaceróz a karcinomů děložního hrdla. V současnosti jsou na trhu dostupné tři profylaktické vakcíny proti HPV infekci bivalentní Cervarix, kvadrivalentní Gardasil (dříve Silgard) a nonavalentní Gardasil9. Všechny tři profylaktické vakcíny vykazují vysoký účinek v prevenci rozvoje prekancerózních lézí. Nejvyšší účinnosti je dosaženo v populaci HPV naivních jedinců. Standardní léčbou závažných cervikálních prekanceróz je jejich chirurgická excize. Avšak doporučené postupy týkající se očkování proti HPV v době konizace nejsou jasně ustanoveny. Ženy s diagnózou těžké cervikální léze většinou nebyly dosud očkovány proti HPV, proto je přínosné porozumět důležitosti a účinnosti HPV vakcinace v době konizace při prevenci recidivujících prekancerózních lézí. Přesná hodnota vakcinace proti HPV v kontextu chirurgické excize prekancerózních lézí zůstává nejasná, ale očkování je rozhodně cenné při snižování rizika recidivy. Zdá se, že načasování očkování před zákrokem je výhodnější. Ideální doba očkování však není stanovena. Na některé z těchto otázek pravděpodobně odpoví výsledky probíhajících randomizovaných kontrolovaných studií. Závěr: Adjuvantní HPV vakcinace v rámci chirurgické léčby cervikální předrakovinové léze je výrazně spojena se sníženým rizikem recidivy. Očkování proti HPV by mělo být silně zváženo jako adjuvantní léčba zejména u mladých pacientek podstupujících konizaci pro těžkou cervikální lézi.
Objective: A review of current knowledge on the efficacy of human papillomavirus (HPV) vaccination in preventing recurrent severe cervical lesions after excisional surgical treatment. Methods and results: HPV infection is necessary for the development of most cervical precancerous lesions and cervical cancers. Currently, three prophylactic vaccines against HPV infection are available on the market: bivalent Cervarix, quadrivalent Gardasil (formerly Silgard) and nonavalent Gardasil9. All three prophylactic vaccines show high effect in preventing the development of precancerous lesions. The highest efficacy is achieved in the HPV naive population. The surgical excision of severe cervical precancers is the standard approach. However, guidelines regarding HPV vaccination at the time of conisation are not clearly determined. Women diagnosed with severe cervical lesions have mostly not been vaccinated against HPV so far. Therefore, it is beneficial to understand the importance and efficacy of HPV vaccination at the time of conisation in preventing recurrent precancerous lesions. The exact value of HPV vaccination in the context of surgical excision of precancerous lesions remains unclear, but vaccination is definitely valuable in reducing the risk of recurrence. Vaccination timing seems to be more favorable before surgery. However, the ideal timing of vaccination is not established. Some of these questions are likely to be answered by the results of ongoing randomized controlled trials. Conclusion: Adjuvant HPV vaccination in the setting of surgical treatment for cervical precancerous lesion is significantly associated with a reduced risk of recurrence. HPV vaccination should be strongly considered as adjuvant therapy, especially in young patients undergoing conisation for a severe cervical lesion.
INTRODUCTION: The standard procedure in cervical cancer is radical hysterectomy and pelvic lymphadenectomy (PLND). Because of the increasing age of women bearing children, fertility has become a major challenge. We present pregnancy results after less radical fertility-sparing surgery in women with IA1, LVSI positive, IA2 and IB1 (<2 cm, infiltration less than half of the cervical stroma). MATERIALS AND METHOD: All women (n = 91) underwent laparoscopic sentinel lymph node mapping with frozen section followed by PLND and "selective parametrectomy" (removal of afferent lymphatic channels from the paracervix) if sentinel nodes (SLN) are negative. If lymph nodes were verified negative by definitive histopathology, patients were treated by simple trachelectomy (IB1) or large cone (IA1/IA2) biopsy 1 week after primary surgery. RESULTS: From 1999 to 2018, 91 women were enrolled in the study (median age 29.1 years, range 21-40). Fertility was spared in 76 (83.5%) women; 13 (17.1%) women did not plan future pregnancy and 63 (82.9%) had pregnancy desires. Fifty-four of 63 women conceived (pregnancy rate 85.7%) and 48 of 63 delivered 58 babies (delivery rate 76.2%). Thirty-nine women delivered in term (67.2%): 13 women between 32 and 36 + 6 weeks of pregnancy, 3 between 28 and 31 + 6 weeks and 3 between 24 and 27 + 6 weeks. Only one woman still plans pregnancy. One woman is currently pregnant. CONCLUSION: The goal of fertility-sparing surgery is to produce good oncological results and promising pregnancy outcomes. Pregnancy results after less radical fertility-sparing procedures show promise (pregnancy rate 82.9% and delivery rate 76.2%).
- MeSH
- cervix uteri patologie MeSH
- dítě MeSH
- dospělí MeSH
- fertilita MeSH
- hysterektomie metody MeSH
- lidé MeSH
- lymfadenektomie MeSH
- mladý dospělý MeSH
- nádory děložního čípku * chirurgie patologie MeSH
- staging nádorů MeSH
- těhotenství MeSH
- výsledek těhotenství * MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The most common cancer in women worldwide is cervical cancer. For early-stage disease the standard treatment is radical hysterectomy. One of the main issues faced by surgeons performing a radical hysterectomy is the wide variation in the terminology used to define the procedure and the nomenclature used to describe the anatomical spaces critical to the success of the surgery. The aim of this review was to synthesize currently used anatomical landmarks with relation to surgical avascular spaces for the performance of radical hysterectomy.A computer-based comprehensive review of the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and SciSearch databases, as well as National Comprehensive Cancer Network and European Society of Gynaecological Oncology guidelines, was performed. With all relevant data collected, and previous anatomical studies during surgeries and on cadavers performed by authors, a manuscript of the definition of avascular spaces, methods of dissection, and anatomical limits was prepared.Avascular pelvic spaces developed during radical hysterectomy, such as the paravesical, pararectal, ureter tunnel, and paravaginal, were considered and included in the manuscript. A clear definition of avascular spaces may aid a better understanding of the anatomical aspects of the radical hysterectomy. It could improve surgeon knowledge of the structures that need to be preserved and those that need to be resected during a radical hysterectomy. Additionally, the detailed exposure of anatomical boundaries will facilitate the appropriate tailored radicality depending on the risk factors of the disease. Moreover, knowledge of these spaces could make pelvic surgery safer and easier for other types of gynecological and non-gynecological procedures.
- MeSH
- disekce MeSH
- hysterektomie * metody MeSH
- lidé MeSH
- nádory děložního čípku * patologie MeSH
- pánev patologie MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.This multicenter cohort study reports on the long-term effects of prenatal exposure to maternal cancer and its treatment on cognitive and behavioral outcomes in 9-year-old children. In total, 151 children (mean age, 9.3 years; range, 7.8-10.6 years) were assessed using a neurocognitive test battery and parent-report behavioral questionnaires. During pregnancy, 109 children (72.2%) were exposed to chemotherapy (only or in combination with other treatment modalities), 18 (11.9%) to surgery only, 16 (10.6%) to radiotherapy, one to trastuzumab, and 16 (10.6%) were not exposed to oncologic treatment. Mean cognitive and behavioral outcomes were within normal ranges. Gestational age at birth showed a positive association with Full Scale Intelligence Quotient (FSIQ), with the average FSIQ score increasing by 1.6 points for each week increase in gestational age (95% CI, 0.7 to 2.5; P < .001). No difference in FSIQ was found between treatment types (F[4,140] = 0.45, P = .776). In children prenatally exposed to chemotherapy, no associations were found between FSIQ and chemotherapeutic agent, exposure level, or timing during pregnancy. These results indicate a reassuring follow-up during the critical maturational period of late childhood, when complex functions develop and rely on the integrity of early brain development. However, associations were observed with preterm birth, maternal death, and maternal education.
- MeSH
- dítě MeSH
- kognice MeSH
- kohortové studie MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- novorozenec MeSH
- předčasný porod * MeSH
- prospektivní studie MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem 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.
PURPOSE: The successful implementation of immune checkpoint inhibitors (ICI) in the clinical management of various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due to immunologic features including limited tumor mutational burden (TMB) and poor lymphocytic infiltration. An autologous dendritic cell (DC)-based vaccine (DCVAC) has recently been shown to be safe and to significantly improve progression-free survival (PFS) in a randomized phase II clinical trial enrolling patients with EOC (SOV01, NCT02107937). PATIENTS AND METHODS: We harnessed sequencing, flow cytometry, multispectral immunofluorescence microscopy, and IHC to analyze (pretreatment) tumor and (pretreatment and posttreatment) peripheral blood samples from 82 patients enrolled in SOV01, with the aim of identifying immunologic biomarkers that would improve the clinical management of patients with EOC treated with DCVAC. RESULTS: Although higher-than-median TMB and abundant CD8+ T-cell infiltration were associated with superior clinical benefits in patients with EOC receiving standard-of-care chemotherapy, the same did not hold true in women receiving DCVAC. Conversely, superior clinical responses to DCVAC were observed in patients with lower-than-median TMB and scarce CD8+ T-cell infiltration. Such responses were accompanied by signs of improved effector functions and tumor-specific cytotoxicity in the peripheral blood. CONCLUSIONS: Our findings suggest that while patients with highly infiltrated, "hot" EOCs benefit from chemotherapy, women with "cold" EOCs may instead require DC-based vaccination to jumpstart clinically relevant anticancer immune responses.
- MeSH
- dendritické buňky MeSH
- epiteliální ovariální karcinom * genetika terapie MeSH
- lidé MeSH
- mutace MeSH
- nádorové biomarkery MeSH
- nádory vaječníků * genetika terapie MeSH
- protinádorové vakcíny * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
BACKGROUND: Surgical treatment of obese female patients represents a real challenge. Over the last decade, minimally invasive techniques for hysterectomy have emerged. These approaches reduce the invasiveness of standard surgical procedures while maintaining efficacy and feasibility. OBJECTIVE: To evaluate the rates of perioperative, early, mid-term and late postoperative complications in very obese [body mass index (BMI) ≥ 35 and < 40 kg/m2] and severely obese (BMI ≥ 40 kg/m2) women who underwent total (non-radical) hysterectomy. DESIGN: A prospective comparative multi-centre non-randomized study. METHODS: In total, 328 consecutive total (non-radical) hysterectomies were performed at seven teaching gynaecological centres. Of these, 153 (46.6%) were performed using an open laparotomy (LT) approach and 175 (53.4%) were performed laparoscopically (LS). All data were collected by medical specialists at the pre-operative examination prior to surgery, during surgery and three times postoperatively (during hospital stay, at 6-week follow-up and 6 months following surgery). Another analysis considered a total of 206 women who underwent laparoscopic hysterectomy. The subjects were divided according to BMI into 120 very obese women (BMI ≥ 35 and < 40 kg/m2) and 86 severely obese women (BMI ≥ 40 kg/m2). RESULTS: The total number of composite perioperative complications was significantly lower in the LS group (p = 0.006). Composite complications occurred significantly more often in patients in the LT group compared with the LS group in the early (p < 0.001) and mid-term (p < 0.001) postoperative periods. In the late postoperative period, the total number of composite postoperative complications did not differ significantly between the groups (p < 0.396). Among 206 patients who underwent laparoscopic hysterectomy, the number of complications was generally low; the rates of composite perioperative (p = 0.393), early (p = 0.642), mid-term (p = 0.738) and late (p = 1) postoperative complications were generally low; and frequency did not differ significantly with BMI. CONCLUSION: The LS approach does not increase intra-operative morbidity associated with surgery, and has significantly better outcomes in terms of the postoperative complication rate.
- MeSH
- délka pobytu MeSH
- hysterektomie škodlivé účinky metody MeSH
- laparoskopie * škodlivé účinky metody MeSH
- lidé MeSH
- následné studie MeSH
- obezita komplikace chirurgie MeSH
- pooperační komplikace epidemiologie etiologie MeSH
- prospektivní studie MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH