Prevalence detekce izolovaných nádorových buněk a mikrometastáz v sentinelové uzlině stoupá díky jejich podrobnému zpracování formou ultrastagingu. Předkládaná práce poskytuje aktuální přehled literatury od ledna roku 2019 do září roku 2024 se zaměřením na nízkoobjemové postižení regionálních uzlin, jeho prevalenci, prognózu a souvislost s molekulární klasifikací. Přítomnost mikrometastáz je aktuálně považována za metastatické postižení lymfatických uzlin, avšak s lepší prognózou než makrometastázy, dle toho je volen i terapeutický postup společný pro obě tyto kategorie uzlinového postižení. Naopak přítomnost izolovaných nádorových buněk není v rámci Mezinárodní federace gynekologie a porodnictví (FIGO) 2023 stagingu považována za uzlinové postižení a neovlivňuje doporučený terapeutický postup, protože doposud nebyly prokázány signifikantní prognostické důsledky jejich přítomnosti.

Due to the implementation of sentinel lymph node ultrastaging, the prevalence of isolated tumor cells and micrometastases have increased. This literature review comprises of articles published between January 2019 and September 2024 aiming at low-volume metastases in regional lymph nodes, their prognosis, and links to molecular classification. Micrometastases are currently considered as having metastatic lymph node involvement; however, they have a better prognosis than macrometastases. Accordingly, therapy is tailored. In contrast, isolated tumor cell presence is not considered metastatic involvement according to International Federation of Gynecology and Obstetrics (FIGO) 2023 staging and does not affect the therapeutic procedure because their significant prognostic importance has not been proven so far.

• Keywords
• nízkoobjemové postižení uzlin,
• MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Neoplasm Metastasis diagnosis   pathology   MeSH
• Neoplasm Micrometastasis MeSH
• Endometrial Neoplasms * diagnosis   epidemiology   complications   MeSH
• Prognosis MeSH
• Sentinel Lymph Node * pathology   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

OBJECTIVES: To assess the diagnostic performance of ultrasonography in pre-operative assessment of lymph nodes in patients with cervical cancer, to compare the outcomes for pelvic and para-aortic regions, and to detect macrometastases and micrometastases separately. METHODS: Patients were retrospectively included if they met the following inclusion criteria: pathologically verified cervical cancer; ultrasonography performed by one of four experienced sonographers; surgical lymph node staging, at least in the pelvic region-sentinel lymph node biopsy or systematic pelvic lymphadenectomy or debulking. The final pathological examination was the reference standard. RESULTS: 390 patients met the inclusion criteria between 2009 and 2019. Pelvic node macrometastases (≥2 mm) were confirmed in 54 patients (13.8%), and micrometastases (≥0.2 mm and <2 mm) in another 21 patients (5.4%). Ultrasonography had sensitivity 72.2%, specificity 94.0%, and area under the curve (AUC) 0.831 to detect pelvic macrometastases, while sensitivity 53.3%, specificity 94.0%, and AUC 0.737 to detect both pelvic macrometastases and micrometastases (pN1). Ultrasonography failed to detect pelvic micrometastases, with sensitivity 19.2%, specificity 85.2%, and AUC 0.522. There was no significant impact of body mass index on diagnostic accuracy. Metastases in para-aortic nodes (macrometastases only) were confirmed in 16 of 71 patients who underwent para-aortic lymphadenectomy. Ultrasonography yielded sensitivity 56.3%, specificity 98.2%, and AUC 0.772 to identify para-aortic node macrometastases. CONCLUSION: Ultrasonography performed by an experienced sonographer can be considered a sufficient diagnostic tool for pre-operative assessment of lymph nodes in patients with cervical cancer, showing similar diagnostic accuracy in detection of pelvic macrometastases as reported for other imaging methods (18F-fluorodeoxyglucose positron emission tomography/CT or diffusion-weighted imaging/MRI). It had low sensitivity for detection of small-volume macrometastases (largest diameter <5 mm) and micrometastases. The accuracy of para-aortic assessment was comparable to that for pelvic lymph nodes, and assessment of the para-aortic region should be an inseparable part of the examination protocol.

• MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymph Node Excision MeSH
• Lymphatic Metastasis * diagnostic imaging   MeSH
• Lymph Nodes * diagnostic imaging   pathology   surgery   MeSH
• Neoplasm Micrometastasis diagnostic imaging   MeSH
• Uterine Cervical Neoplasms * diagnostic imaging   pathology   surgery   MeSH
• Preoperative Care methods   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Sensitivity and Specificity MeSH
• Ultrasonography * methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: We found a need for balancing the application of clinical guidelines and tailored approaches to follow-up of cervical cancer (CC) patients in the lymph node micrometastatic (MICs) setting. This review aimed to determine the current knowledge of management of MIC-positive CC cases. METHODOLOGY: We addressed prognostic and risk of recurrence monitoring impacts associated with MIC+ cases. The electronic databases for literature and relevant articles were analysed. RESULTS: Fifteen studies, (4882 patients), were included in our systematic review. While the results show that MICs significantly worsen prognosis in early CC. A tertiary prevention algorithm for low volume lymph node disease may stratify follow-up according to the burden of nodal disease and provide data that helps improve follow-up performance. CONCLUSION: MICs worsen prognosis and should be managed as suggested by the algorithm. However, this algorithm must be externally validated. The clinical impact of isolated tumor cells (ITC) remains unclear.

• MeSH
• Humans MeSH
• Neoplasm Recurrence, Local prevention & control   pathology   MeSH
• Lymphatic Metastasis * MeSH
• Lymph Nodes pathology   MeSH
• Neoplasm Micrometastasis * pathology   MeSH
• Uterine Cervical Neoplasms * pathology   diagnosis   prevention & control   MeSH
• Prognosis MeSH
• Tertiary Prevention methods   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Systematic Review MeSH

BACKGROUND: In cervical cancer, presence of lymph-node macrometastases (MAC) is a major prognostic factor and an indication for adjuvant treatment. However, since clinical impact of micrometastases (MIC) and isolated tumor-cells (ITC) remains controversial, we sought to identify a cut-off value for the metastasis size not associated with negative prognosis. METHODS: We analyzed data from 967 cervical cancer patients (T1a1L1-T2b) registered in the SCCAN (Surveillance in Cervical CANcer) database, who underwent primary surgical treatment, including sentinel lymph-node (SLN) biopsy with pathological ultrastaging. The size of SLN metastasis was considered a continuous variable and multiple testing was performed for cut-off values of 0.01-1.0 mm. Disease-free survival (DFS) was compared between N0 and subgroups of N1 patients defined by cut-off ranges. RESULTS: LN metastases were found in 172 (18%) patients, classified as MAC, MIC, and ITC in 79, 54, and 39 patients, respectively. DFS was shorter in patients with MAC (HR 2.20, P = 0.003) and MIC (HR 2.87, P < 0.001), while not differing between MAC/MIC (P = 0.484). DFS in the ITC subgroup was neither different from N0 (P = 0.127) nor from MIC/MAC subgroups (P = 0.449). Cut-off analysis revealed significantly shorter DFS compared to N0 in all subgroups with metastases ≥0.4 mm (HR 2.311, P = 0.04). The significance of metastases <0.4 mm could not be assessed due to limited statistical power (<80%). We did not identify any cut-off for the size of metastasis with significantly better prognosis than the rest of N1 group. CONCLUSIONS: In cervical cancer patients, the presence of LN metastases ≥0.4 mm was associated with a significant negative impact on DFS and no cut-off value for the size of metastasis with better prognosis than N1 was found. Traditional metastasis stratification based on size has no clinical implication.

• MeSH
• Sentinel Lymph Node Biopsy MeSH
• Humans MeSH
• Lymphatic Metastasis pathology   MeSH
• Lymph Nodes pathology   MeSH
• Neoplasm Micrometastasis pathology   MeSH
• Uterine Cervical Neoplasms * surgery   pathology   MeSH
• Breast Neoplasms * pathology   MeSH
• Sentinel Lymph Node * pathology   MeSH
• Neoplasm Staging MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVE: The etiology of inferior oncologic outcomes associated with minimally invasive surgery for early-stage cervical cancer remains unknown. Manipulation of lymph nodes with previously unrecognized low-volume disease might explain this finding. We re-analyzed lymph nodes by pathologic ultrastaging in node-negative patients who recurred in the LACC (Laparoscopic Approach to Cervical Cancer) trial. METHODS: Included patients were drawn from the LACC trial database, had negative lymph nodes on routine pathologic evaluation, and recurred to the abdomen and/or pelvis. Patients without recurrence or without available lymph node tissue were excluded. Paraffin tissue blocks and slides from all lymph nodes removed by lymphadenectomy were re-analyzed per standard ultrastaging protocol aimed at the detection of micrometastases (>0.2 mm and ≤2 mm) and isolated tumor cells (clusters up to 0.2 mm or <200 cells). RESULTS: The study included 20 patients with median age of 42 (range 30-68) years. Most patients were randomized to minimally invasive surgery (90%), had squamous cell carcinoma (65%), FIGO 2009 stage 1B1 (95%), grade 2 (60%) disease, had no adjuvant treatment (75%), and had a single site of recurrence (55%), most commonly at the vaginal cuff (45%). Only one patient had pelvic sidewall recurrence in the absence of other disease sites. The median number of lymph nodes analyzed per patient was 18.5 (range 4-32) for a total of 412 lymph nodes. A total of 621 series and 1242 slides were reviewed centrally by the ultrastaging protocol. No metastatic disease of any size was found in any lymph node. CONCLUSIONS: There were no lymph node low-volume metastases among patients with initially negative lymph nodes who recurred in the LACC trial. Therefore, it is unlikely that manipulation of lymph nodes containing clinically undetected metastases is the underlying cause of the higher local recurrence risk in the minimally invasive arm of the LACC trial.

• MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymph Node Excision MeSH
• Lymphatic Metastasis pathology   MeSH
• Lymph Nodes pathology   MeSH
• Neoplasm Micrometastasis pathology   MeSH
• Uterine Cervical Neoplasms * pathology   MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Research Support, N.I.H., Extramural MeSH

Zhoubné nádory štítné žlázy jsou vzácná nádorová onemocnění. V endokrinologii však patří k největší skupině nádorových onemocnění (tvoří okolo 90 % nádorů).1 Diagnostika a léčba zhoubných nádorů štítné žlázy je mezioborová. Kromě endokrinologa, odborníka v oboru nukleární medicíny, chirurga, radiologa a radiačního onkologa se v posledních letech podílí na diagnostice i léčbě těchto zhoubných nádorů klinický onkolog, molekulární biolog a genetik. V roce 1993 byla objevena příčina familiární formy medulárního karcinomu – aktivující mutace protoonkogenu RET (REarranged during Transfection).2 Objev vedl k rozvoji nových diagnostických a terapeutických postupů, umožnil profylaktický screening v postižených rodinách.

Malignant tumors of the thyroid gland are rare diseases. In endocrinology, however, it belongs to the largest group of cancer diseases (about 90% tumors). Diagnosis and treatment is interdisciplinary. In addition to an endocrinologist, a nuclear medicine specialist, a surgeon, a radiologist and a radiation oncologist, a molecular biologist and a geneticist have been involved in the diagnosis and treatment of this cancer in recent years. In 1993, the cause of familial forms of medullary carcinoma was discovered - an activating mutation of the RET (REarranged during Transfection) proto-oncogene. The discovery led to the development of new diagnostic and therapeutic procedures, enabled prophylactic screening in affected families.

• MeSH
• Survival Analysis MeSH
• Cytostatic Agents therapeutic use   MeSH
• Thyroid Hormones therapeutic use   MeSH
• Tyrosine Kinase Inhibitors therapeutic use   MeSH
• Combined Modality Therapy MeSH
• Neoplasm Micrometastasis MeSH
• Mutation MeSH
• Thyroid Neoplasms * diagnostic imaging   classification   therapy   MeSH
• Proto-Oncogenes genetics   MeSH
• Iodine Radioisotopes therapeutic use   MeSH
• Patient Care Team MeSH

OBJECTIVE: In order to define the clinical significance of low-volume metastasis, a comprehensive meta-analysis of published data and individual data obtained from articles mentioning micrometastases (MIC) and isolated tumor cells (ITC) in cervical cancer was performed, with a follow up of at least 3 years. METHODS: We performed a systematic literature review and meta-analysis, following Cochrane's review methods guide and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome was the disease-free survival (DFS), and the secondary outcome was the overall survival (OS). The hazard ratio (HR) was taken as the measure of the association between the low-volume metastases (MIC+ITC and MIC alone) and DFS or OS; it quantified the hazard of an event in the MIC (+/- ITC) group compared to the hazard in node-negative (N0) patients. A random-effect meta-analysis model using the inverse variance method was selected for pooling. Forest plots were used to display the HRs and risk differences within individual trials and overall. RESULTS: Eleven articles were finally retained for the meta-analysis. In the analysis of DFS in patients with low-volume metastasis (MIC + ITC), the HR was increased to 2.60 (1.55-4.34) in the case of low-volume metastasis vs. N0. The presence of MICs had a negative prognostic impact, with an HR of 4.10 (2.71-6.20) compared to N0. Moreover, this impact was worse than that of MIC pooled with ITCs. Concerning OS, the meta-analysis shows an HR of 5.65 (2.81-11.39) in the case of low-volume metastases vs. N0. The presence of MICs alone had a negative effect, with an HR of 6.94 (2.56-18.81). CONCLUSIONS: In conclusion, the presence of MIC seems to be associated with a negative impact on both the DFS and OS and should be treated as MAC.

• MeSH
• Adenocarcinoma pathology   therapy   MeSH
• Sentinel Lymph Node Biopsy MeSH
• Humans MeSH
• Lymphatic Metastasis MeSH
• Lymph Nodes pathology   MeSH
• Neoplasm Micrometastasis pathology   MeSH
• Survival Rate MeSH
• Uterine Cervical Neoplasms pathology   therapy   MeSH
• Disease-Free Survival MeSH
• Sentinel Lymph Node pathology   MeSH
• Carcinoma, Squamous Cell pathology   therapy   MeSH
• Neoplasm Staging MeSH
• Tumor Burden MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH

PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

• MeSH
• Time Factors MeSH
• Radiation Dosage * MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymph Node Excision * adverse effects   mortality   MeSH
• Lymphatic Metastasis MeSH
• Neoplasm Micrometastasis MeSH
• Vulvar Neoplasms mortality   pathology   therapy   MeSH
• Prospective Studies MeSH
• Aged MeSH
• Sentinel Lymph Node pathology   radiation effects   surgery   MeSH
• Neoplasm Staging MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Webcast MeSH

Cíl studie: Shrnutí současné evidence o významu sentinelové uzliny u pacientek s karcinomem děložního hrdla. Typ studie: Přehledový článek. Název a sídlo pracoviště: Gynekologicko-porodnická klinika VFN a 1. LF UK Praha. Metodika: Byla provedena systematická rešerše recenzovaných článků stěžejních periodik a vědeckých týmů věnujících se problematice. Využita byla databáze PubMed s klíčovými slovy a zhodnocena osobní kontinuální klinická zkušenost s managementem pacientek s karcinomem děložního hrdla pomocí biopsie sentinelové uzliny. Výsledky: Biopsie sentinelové uzliny má své pevné místo v managementu pacientek s časným karcinomem děložního hrdla. Jedná se o metodu s vysokou úspěšností detekce v rukou zkušeného operatéra, s vysokou senzitivitou a nízkou falešnou negativitou pro stav pánevních uzlin. Intraoperační vyšetření sentinelové uzliny je málo přesné, mine až polovinu všech metastáz. Definitivní extenzivní patologické zpracování pomocí protokolu pro ultrastaging detekuje navíc zhruba 10 % pacientek s malými metastázami, tzv. mikrometástázami, které by jinak byly považovány za uzlinově negativní. Data o prognostickém významu mikrometastatického postižení sentinelové uzliny jsou limitována, současně existuje narůstající evidence o negativním vlivu mikrometastázy na parametry přežití a tyto pacientky by měly mít identický management jako ty s makrometastázou. Závěr: Současným doporučeným postupem chirurgické léčby pacientek s časným karcinomem děložního hrdla je biopsie sentinelové uzliny společně se systematickou pánevní lymfadenektomií. Otázku onkologické bezpečnosti méně radikálního přístupu spočívajícího jen v biopsii sentinelové uzliny odpoví právě probíhající prospektivní onkologické studie.

Objective: Summary of current evidence about sentinel lymph node concept in early stages cervical cancer. Design: Review. Setting: Department of Obstetrics and Gynaecology, General University Hospital, First Faculty of Medicine, Charles University, Prague. Methods: First, a comprehensive search of a peer-reviewed journals in gynaecological oncology was conducted based on a wide range of key words used in PubMed database. Second, the reference section for each article found was searched in order to find additional articles. Third, extensive personal clinical and scientifical experience with sentinel lymph node concept in cervical cancer was utilized. Results: Sentinel lymph node biopsy is routinely used in the management of early stages cervical cancer with high detection rate in skilled surgeon's hands. It has high sensitivity and low false negative rate. The intraoperative sentinel lymph node examination (i.e. frozen section) has low accuracy because it fails to detect about half of cases with lymph node involvement. Final pathological examination with intensive protocol for ultrastaging detects additional 10% of patients with small metastases (i.e. micrometastasis), who would be otherwise missed. There are limited data about the importance of micrometastasis involvement in sentinel lymph node; there is also growing evidence about negative prognostic impact and patients with micrometastasis should be managed with the same criteria as patients with macrometastasis. Conclusion: Sentinel lymph node biopsy followed by full pelvic lymph node dissection is currently standard of care until ongoing prospective trials answer question about oncological safety of less radical surgical approach with sentinel lymph node biopsy only.

• Keywords
• intraoperační vyšetření,
• MeSH
• Sentinel Lymph Node Biopsy * MeSH
• Diagnostic Errors MeSH
• False Negative Reactions MeSH
• Humans MeSH
• Neoplasm Micrometastasis diagnosis   MeSH
• Uterine Cervical Neoplasms * diagnosis   MeSH
• Prognosis MeSH
• Sentinel Lymph Node MeSH
• Sensitivity and Specificity MeSH
• Neoplasm Staging MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

BACKGROUND AND OBJECTIVES: Utilisation of the one-step nucleic acid amplification (OSNA) molecular biology method for the detection of the metastatic involvement of sentinel lymph nodes (SLNs) in endometrial cancer (EC) patients. A comparison with histopathological ultrastaging and a description of the clinical consequences. METHODS: Surgically treated EC patients underwent detection of SLNs. Nodes greater than 5 mm were cut into sections 2-mm thick parallel to the short axis of the node. Odd sections were examined according to the OSNA method, while even ones according to an appropriate ultrastaging protocol. Nodes less than or equal to 5 mm were cut into halves along the longitudinal axis with one half examined according to the OSNA method and the other half by ultrastaging. RESULTS: Fifty-eight patients were included and 135 SLNs were acquired. Both ultrastaging and OSNA agreed on 116 results. According to the OSNA method, 20.69% more patients were classified into International Federation of Gynecology and Obstetrics (FIGO) stage III. When comparing the results of the OSNA method to the conclusions of ultrastaging as a reference method, sensitivity of 90.9%, specificity of 85.5% and concordance of 85.9% were attained. CONCLUSIONS: The results of the OSNA method showed a higher frequency of detection of micrometastases and included 20.69% more patients into FIGO stage III.

• MeSH
• Adenocarcinoma, Clear Cell genetics   secondary   surgery   MeSH
• Sentinel Lymph Node Biopsy MeSH
• Adult MeSH
• Keratin-19 genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphatic Metastasis MeSH
• Neoplasm Micrometastasis MeSH
• Survival Rate MeSH
• Biomarkers, Tumor genetics   MeSH
• Endometrial Neoplasms genetics   pathology   surgery   MeSH
• Follow-Up Studies MeSH
• Nucleic Acids analysis   genetics   MeSH
• Intraoperative Period MeSH
• Prognosis MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Sentinel Lymph Node pathology   surgery   MeSH
• Cystadenocarcinoma, Serous genetics   secondary   surgery   MeSH
• Nucleic Acid Amplification Techniques methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH