Klinicka onkologie

A unique case of a giant ovarian mucinous cystadenoma causing an acute renal failure and compartment syndrome

Mucinous cystadenoma of the ovary is a common gynecologic tumor that usually has a very favorable prognosis. However, if it is not early detected and removed, it can grow to a large size and may cause serious health complications. A 65-year-old woman was transported to the hospital by the emergency medical service due to overall weakness, markedly enlarged abdomen reminiscent of ascites, breathing difficulties, and swollen legs with eczematous ulcers. Laboratory parameters showed an acute renal insufficiency. Imaging scans revealed a giant solid cystic tumor mass filling the whole abdominopelvic cavity, which caused a compartment syndrome of the lower limbs. After relieving puncture and drainage of 6 L of fluid from the cyst, laparotomy had been performed. Grossly, the entire abdominal cavity was filled with a huge cystic tumor originating from the left ovary. During its surgical preparation, a total of 17 L of fluid was evacuated from it. Then, adnexectomy was made. A bio-psy sample consisted of an irregular, artificially teared multicystic tumor about 60 cm in the largest dimension. Histology confirmed a benign mucinous cystadenoma. After tumor removal, the patient's health condition and laboratory parameters improved. We described a unique case of an extremely huge ovarian mucinous cystadenoma that led to a life-threating event of the patient. We tried to point out that even a "common" benign tumor may lead to clinically malignant consequences and its management requires a multidisciplinary approach.

Cervical cancer in pregnancy

Cervical cancer is one of the most frequent cancers in pregnant women, despite this combination being a rare condition. More than 70% of cases are dia-gnosed in early stages and its treatment can be postponed after the delivery. Invasive cancer dia-gnosis in pregnancy is difficult for a patient, her family and doctors. A multidisciplinary team should take care of the patient and foetus and patients wishes are respected regarding her treatment and pregnancy. Radiotherapy in pregnancy is contraindicated. Neoadjuvant or adjuvant chemotherapy is therefore a main treatment method in patients with high risk disease either during pregnancy, or after the delivery. Neoadjuvant chemotherapy choice, delivery timing and definitive treatment are keys to mothers and childs health. Palliative treatment during pregnancy is extremely rare and the prognosis is poor. Bevacizumab and pembrolizumab are promising in the palliative treatment of non-pregnant patients. Neither bio-logical therapy by bevacizumab, nor immunotherapy by pembrolizumab can be administered to pregnant patient due to their mechanisms of action. This overviews aim is to analyse data of cervical cancer treatment for pregnant women, focusing on dia-gnostics, therapy and delivery timing and treatment modalities choice according to the stage of the disease and gestational age. Individual approach is always necessary; our aim is, however, to emphasise current evidence-based recommendations in pregnancy. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Total mesometrial resection for the treatment of cervical cancer – an exploratory study of feasibility, safety and oncological outcomes in developing countries

Total mesometrial resection (TMMR) has shown excellent locoregional control for treatment of cervical cancer without adjuvant radiation therapy in highly selected centers. However, this procedure was never evaluated in resource-limited setting. We hypothesized that the procedure can be reproduced outside the university centers without compromising results. This is a retrospective, observational, multicenter cohort study of patients with IB1-IIB cervical cancer who underwent TMMR in developing countries and omitted adjuvant radiation therapy. A total of 124 patients who met the inclusion criteria were identified between 2015 and 2024 in three centers. The median follow-up was 29 months. The relapse rate was 6.1% (2 out of 33) for IB1, 3% (1 out of 33) for IB2, 11.1% (2 out of 18) for IB3, 20% (1 out of 5) for IIA1, and 16% (6 out of 24) for node-positive patients. No relapses were detected among IIA2 and IIB stages (3 and 8 patients, respectively). There was no significant difference (P = 0.36) in the relapse rate between patients who met the Sedlis criteria (2.9%) and those who did not (8.8%). According to the study, TMMR outcomes can be reproduced without compromising oncologic outcomes. However, prospective evaluation, longer follow-up and a larger cohort are needed to confirm these preliminary data.

Current complex treatment for cervical cancer

Cervical cancer has shown declining incidence and mortality in recent years, yet it remains a serious societal problem. This is mainly due to its prevalence in younger age groups and the relatively difficult treatment of advanced stages. Treatment of the early stages is predominantly in the hands of gynecologists, while modern radiation therapy combined with systemic therapy is now the standard treatment for advanced stages. More controversial is the indication and position of neoadjuvant systemic therapy before surgery or radiotherapy. In addition to chemotherapy, the role of immunotherapy in metastatic disease is increasing. The addition of immunotherapy to radiation therapy in locally advanced disease also improves oncological outcomes. This article summarizes current primarily nonsurgical therapies and outlines directions in the treatment of cervical cancer.

Germline mutations in RAD51C and RAD51D and hereditary predisposition to ovarian cancer

Ovarian cancer is one of the most common gynecologic cancers with the highest mortality rate over a long period. Genetic predisposition to ovarian cancer is unusually high. In the Czech Republic, causal mutation in any ovarian cancer predisposition gene is identified in approximately 30% of the ovarian cancer patients. Therefore, according to the current guidelines, all ovarian cancer patients should be provided with genetic testing. The BRCA1 and BRCA2 are the two major ovarian cancer predisposition genes. Nevertheless, mutations in other predisposition genes, including RAD51C and RAD51D, are associated with high ovarian cancer risk. Mutations in RAD51C and RAD51D are found in 1% of ovarian cancer patients in each respective gene. Currently, identification of germline mutation in RAD51C and RAD51D is primarily of preventive importance but it potentially could make a prognostic difference. The aim of this review is to summarize the recent RAD51C and RAD51D knowledge, including the biological function, cancer risks associated with germline mutations, and recommendations for mutation carriers.

Chemoradiotherapy in the treatment of cervical cancer – a single institution retrospective review

The aim of this study is a retrospective analysis of treatment outcomes and toxicity in a group of patients with cervical cancer who underwent (chemo) radiotherapy at the Institute of Radiation Oncology in Bulovka University Hospital in Prague in the period 2014-2017. During this period, 141 patients were treated, 105 (74.5%) of them underwent combined (chemo) radiotherapy with radical intent and palliative radiotherapy was performed in 36 (25.5%) cases. According to the International Federation of Gynecology and Obstetrics (FIGO) 2009 classification, the most numerous stages were IIB in 39 (27.7%) and IIIB in 64 (45.4%) cases; according to FIGO 2018, a significant number of newly established stages is evident: IIIC1 in 55 (39.0%) patients and IIIC2 in 22 (15.6%) cases. The median progression-free survival (PFS) and overall survival (OS) reached 31.3, resp. 40.1 months in the whole group. In the subgroup of patients treated with radical intent, the median PFS was 44.0 months and OS 48.8 months; in the palliative subgroup, the median PFS was 9.4 months and OS 14.8 months. In a radically treated subgroup, 7 (6.7%) patients had gastrointestinal or genitourinary manifestations of G3-4 toxicity, and overall acute toxicity (including skin and haematological reactions) of G3-4 occurred in 18 (17.1%) patients. Late toxicity of G3-4 was reported in 13 (12.4%) cases. Patients who underwent complete brachytherapy (BRT) showed significantly better survival compared to patients with a lower number of BRT fractions. The prognostic potential of PS (performance status) and anemia was confirmed; significantly longer overall survival was observed in patients in good general condition or in those without anemia. Our results confirmed the key role of BRT for the delivery of the curative dose to the target volume. The prognostic role of PS and anemia is evident. The side effects were in acceptable limits but we expect improvements because of the use of modern radiotherapy technologies.

Practical recommendations for the use of PARP inhibitors in the treatment of ovarian cancer

There is no doubt that PARP inhibitors (PARPi) have significantly improved the prognosis of patients with advanced-stage ovarian cancer. In the history of treatment for this disease, their impact is second only to the introduction of platinum-based chemotherapy. As with any new therapeutic modality, integrating PARPi into routine clinical practice is a complex process. In the Czech Republic, some agents, combinations, or indications are not reimbursed, and indication criteria often require several conditions to be met simultaneously. These factors may lead to uncertainties in the practical use of PARPi. This article aims to highlight and discuss areas where such uncertainties may arise in clinical practice.

The metabolomic profile features of some biological fluids in serous ovarian adenocarcinoma patients

The search for effective biomarkers for ovarian cancer (OC) early diagnosis is an urgent task of modern oncogynecology. Metabolic profiling by ultra-high performance liquid chromatography and mass spectrometry (UHPLC-MS) provides information on the totality of all low molecular weight metabolites of patient's biological fluids sample, reflecting the processes occurring in the body. The aim of the study was to research blood plasma and urine metabolomic profile of patients with serous ovarian adenocarcinoma by UHPLC-MS. To perform metabolomic analysis, 60 blood plasma samples and 60 urine samples of patients diagnosed with serous ovarian carcinoma and 20 samples of apparently healthy volunteers were taken. Chromatographic separation was performed on a Vanquish Flex UHPLC System chromatograph (Thermo Scientific, Germany). Mass spectrometric analysis was performed on an Orbitrap Exploris 480 (Thermo Scientific, Germany) equipped with an electrospray ionization source. Bioinformatic analysis was performed using Compound Discoverer Software (Thermo Fisher Scientific, USA), statistical data analysis was performed in the Python programming language using the SciPy library. Using UHPLC-MS, 1,049 metabolites of various classes were identified in blood plasma. In patients with OC, 8 metabolites had a significantly lower concentration (P < 0.01) compared with conditionally healthy donors, while the content of 19 compounds, on the contrary, increased (P < 0.01). During the metabolomic profiling of urine samples, 417 metabolites were identified: 12 compounds had a significantly lower concentration compared to apparently healthy individuals, the content of 14 compounds increased (P < 0.01). In patients with ovary serous adenocarcinoma, a significant change in the metabolome of blood plasma and urine was found, expressed in abnormal concentrations of lipids and their derivatives, fatty acids and their derivatives, acylcarnitines, phospholipids, amino acids and their derivatives, derivatives of nitrogenous bases and steroids. At the same time, kynurenine, myristic acid, lysophosphatidylcholine and L-octanoylcarnitine are the most promising markers of this disease. The revealed changes in the metabolome can become the basis for improving approaches to the diagnosis of serous ovarian adenocarcinoma.

The guidelines for clinical practice for carriers of germline mutations in hereditary breast, ovarian, prostate, and pancreatic cancer predisposition genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 (4.2024)

The Guidelines for Clinical Practice for carriers of pathogenic variants in clinically relevant cancer predisposition genes define the steps of primary and secondary prevention that should be provided to these individuals at high risk of developing hereditary cancer in the Czech Republic. The drafting of the guidelines was organized by the Oncogenetics Working Group of the Society for Medical Genetics and Genomics of J. E. Purkyně Czech Medical Society (SLG ČLS JEP) in cooperation with the representatives of oncology and oncogynecology. The guidelines are based on the current recommendations of the National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO) and take into account the capacity of the Czech healthcare system.

Staging for endometrial carcinoma FIGO 2023 and its relevance for clinical practice

International Federation of Gynaecology and Obstetrics (Fédération Internationale de Gynécologie et d'Obstétrique - FIGO) introduced a new staging system for endometrial carcinoma - FIGO 2023 - in June 2023. The new staging system differs significantly from previous versions. The new system represents a significant departure from the traditional staging systems for other gynaecological cancers, as the definition of individual stages includes not only the traditional anatomical extent of the tumour, but also the molecular profile of the tumour and other histopathological parameters - histological type of tumour, tumour grade and the presence of substantial lymphovascular invasion. The new system defines stages I and II in a completely different way and expands the definition of stages III and IV, allowing for different types of tumour spread outside the uterus. The introduction of molecular testing is the main change in the new staging system. When certain molecular markers are detected, stage I or II is completely changed. By including these non-anatomical parameters, the FIGO 2023 staging system improves the accuracy of a patient's prognosis at a specific stage with better options for individualized treatment, including the use of immunotherapy. Another goal was to synchronise staging as much as possible with the recommendations of three professional societies: the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP). The staging system for carcinosarcoma remains identical to the staging system for endometrial cancer. This article presents an overview of the new FIGO 2023 endometrial cancer staging system and discusses its advantages and disadvantages for clinical practice.

Meigs’ syndrom

Meigs syndrome is defined by the presence of a benign ovarian tumor, ascites, and pleural effusion (predominantly on the right side). A characteristic sign of Meigs syndrome is the complete disappearance of exudate after surgical resection of the ovarian tumor. We present a case report of a 58-year-old patient admitted for an advanced ovarian tumor with pleural effusion, ascites, and tumor marker elevation typical for ovarian cancer. Cytological examination of ascites and pleural effusion was repeatedly negative for malignancy. Histopathological examination of the bio-psied tissue was concluded as low-grade mesenchymal neoplasia. The second opinion of histopathological examination was concluded as low grade fibroblastic pelvic tumor without the possibility of exact specification. Dia-gnoses of desmoid fibromatosis and low-grade fibromyxiod sarcoma (less likely) were considered. Surgical resection was indicated, and a large tumor with numerous adhesions to the uterus, bladder, and thin loops with a noticeably thickened peritoneum were perioperatively described. Histologically, left ovarian fibroma with productive peritonitis and sanguine-induced ascites was dia-gnosed. Due to the clinical findings and the result of the histopathological examination, the case was classified as Meigs syndrome. Two months after the surgery, the ascites and pleural effusion disappeared, and the tumor marker levels normalized. The present case report documents that it is always necessary to consider diseases other than those most likely at the outset, as the treatment algorithm and prognosis of these rare diseases may differ significantly.

Primary peritoneal carcinoma and ovarian carcinoma – a ten-year comparative analysis

Primary peritoneal carcinoma (PPC) at presentation often masquerades as epithelial ovarian carcinoma (OC) but behaves different with respect to treatment response, recurrence patterns and has inferior outcomes. The objective of this study is to compare the clinicopathological features and survival outcomes of PPC and OC. Prospectively maintained database of patients presenting to the gynecologic oncology department at a tertiary hospital was reviewed between 1st January 2010 and 31st December 2020. A comparative analysis of high-grade serous stage III/IV PPC and OC was done. Demographics, treatment details, complications and survival outcomes were collected from electronic medical records. 151 OC and 69 PPC patients were included. A higher proportion of women with PPC had reduced performance status prior to hysterectomy with salpingo-oophorectomy, a shorter symptom to treatment interval, and large volume ascites. A significantly lower number of women with PPC (4.3 vs. 46.1%; P < 0.001) underwent primary cytoreduction, had a lower median surgical complexity score (3 vs. 4; P < 0.001) but higher recurrence rates (66.7 vs. 47.0%; P = 0.041) as compared to the patients with OC. The median progression-free survival (PFS) was 18 (15-20) months in PPC and 23 (17-28) months in OC patients (log-rank P = 0.034), while the median overall survival (OS) was similar (44 vs. 48 months; log-rank P = 0.696). The presence of extraperitoneal disease and interval cytoreduction was associated with shorter PFS. Suboptimal cytoreduction and delay in adjuvant chemotherapy beyond 6 weeks post-surgery was associated with reduced OS. PPC is an aggressive disease with lower PFS compared to OC. Commonly presenting with large volume carcinomatosis, it is not amenable for primary cytoreduction, making the usage of neoadjuvant chemotherapy a common practice and pragmatic approach.

Tailoring postoperative management through sentinel lymph node biopsy in low- and intermediate-risk endometrial cancer – the SENTRY clinical trial

While total hysterectomy and bilateral salpingo-oophorectomy without lymph node staging are standard for low- and intermediate-risk endometrial cancer, certain histopathologic factors revealed after surgery can necessitate additional interventions. Our study assessed the influence of sentinel lymph node biopsy on postoperative decision-making. In the SENTRY trial (July 2021 - February 2023), we enrolled patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IA-IB low-grade endometrioid endometrial cancer. Laparoscopic sentinel lymph node mapping using indocyanine green was performed alongside total hysterectomy with bilateral salpingo-oophorectomy. Subsequent management changes based on sentinel lymph node biopsy results were evaluated. The trial was registered at ClinicalTrials.gov (NCT04972682). Of the 100 enrolled participants, a bilateral detection rate of 91% was observed with a median detection time of 10 min (interquartile range 8-13 min). Sentinel lymph node metastases were found in 8% (N = 8) of participants. Postoperative FIGO staging increased in 15% (N = 15) and decreased in 5% (N = 5) of patients. Sentinel lymph node biopsy results altered the adjuvant treatment plan for 20% (N = 20): external beam radiotherapy was omitted in 12% (N = 12) while 6% (N = 6) had external beam radiotherapy +/- systemic chemotherapy added due to sentinel lymph node metastases. In 2% (N = 2), the external beam radiotherapy field was expanded with the paraaortic region. No intraoperative complications were reported and no 30-day major morbidity and mortality occurred. Throughout a median follow-up of 14 (95% CI 12-15 months, neither patient-reported lymphedema nor pelvic recurrence surfaced in the cohort. Sentinel lymph node biopsy using indocyanine green is a safe procedure and allows tailoring adjuvant therapy in presumed low- and intermediate-risk endometrial cancer. It assists in avoiding external beam radiotherapy overtreatment and introducing additional modalities when necessary.

Potential application of body fluids autofluorescence in the non-invasive diagnosis of endometrial cancer

Endometrial carcinoma (EC) is the most common cancer of the female reproductive tract in developed countries. The prognosis and 5-year survival rates are closely tied to the stage diagnosis. Current routine diagnostic methods of EC are either lacking specificity or are uncomfortable, invasive and painful for the patient. As of now, the gold diagnostic standard is endometrial biopsy. Early and non-invasive diagnosis of EC requires the identification of new biomarkers of disease and a screening test applicable to routine laboratory diagnostics. The application of untargeted metabolomics combined with artificial intelligence and biostatistics tools has the potential to qualitatively and quantitatively represent the metabolome, but its introduction into routine diagnostics is currently unrealistic due to the financial, time and interpretation challenges. Fluorescence spectral analysis of body fluids utilizes autofluorescence of certain metabolites to define the composition of the metabolome under physiological conditions. This review highlights the potential of fluorescence spectroscopy in the early detection of EC. Data obtained by three-dimensional fluorescence spectroscopy define the quantitative and qualitative composition of the complex fluorescent metabolome and are useful for identifying biochemical metabolic changes associated with endometrial carcinogenesis. Autofluorescence of biological fluids has the prospect of providing new molecular markers of EC. By integrating machine learning and artificial intelligence algorithms in the data analysis of the fluorescent metabolome, this technique has great potential to be implemented in routine laboratory diagnostics.

Molecular testing of endometrial carcinoma in real-world clinical practice

Molecular classification has brought significant changes in the management of endometrial cancer (EC). In this article, we aim to analyze our first experience with an implementation of molecular testing into daily clinical practice. In all newly diagnosed EC, the status of mismatch repair (MMR) and p53 proteins has been evaluated immunohistochemically as a part of the routine histopathological examination since May 2021. In tumors that do not meet clinical criteria for a low risk and those with MMR deficiency or p53 mutation, the molecular genetic testing of the POLE gene is performed as well. Recommendations for adjuvant treatment or follow-up are subsequently made based on the risk of recurrence. Genetic counselling is proposed to all patients with MMR-deficient tumors or family history of cancer. A total of 85 patients with newly diagnosed EC between May 2021 and May 2022 were enrolled in the analysis. The median age was 66 years. The results of molecular testing were as follows: 22 (26%) MMR-deficient, 8 (9%) p53-mutated and none POLE-ultramutated of those 40 tumors with performed POLE sequencing. A total of 46 (51%) patient had a low risk, 2 (2%) intermediate, 14 (16%) high-intermediate and 20 (24%) patients had a high risk of recurrence. Advanced or metastatic diseases were diagnosed in 6 (7%) patients. The median time between surgery and multidisciplinary tumor board decision was 21 days (8-36). A total of 76 (90%) patients underwent the whole treatment plan according to the recurrence risk. At the time of analysis, the results of genetic testing were available in 18 patients and revealed 4 (22%) carriers of a pathogenic variant in any of the genes associated with Lynch syndrome. Molecular testing combining immunohistochemical analyses of MMR and p53 proteins in all newly diagnosed EC patients with sequencing analysis of POLE in those with non-low-risk disease is feasible and does not prolong the time needed for treatment decision.