Rola HE4 w różnicowaniu złośliwych i niezłośliwych patologii endometrium

Objectives: The incidence of endometrial cancer is constantly growing. More aggressive types of endometrial cancer as well as the incidence in younger women is being observed. More than 80% of cases is diagnosed in early stages due to early symptoms like abnormal bleeding. The remaining 20% of asymptomatic cases of endometrial cancer as well as the cases of false negative histopathological diagnoses are mostly the incidences of serous endometrial cancer and are a true diagnostic and therapeutic challenge. This was the reason of our study in which we proposed investigation of HE4 levels as a complementary diagnostic method in management and diagnosing of EC. Material and methods: Serum HE4 level was measured in 92 patients with abnormal vaginal bleeding. Based on histhology after curretage the study group was divided into the benign and malignant endometrial pathology groups. Statistical analysis was performed using Mann-Whitney test Results: The difference of serum HE4 level between benign endometrial pathology and cancer was significant (p = 0.000) and the cut-off for identification of patients with endometrial cancer was 58.08 pmol/l. There was a significant difference between G2 and G3 endometrial cancer, and G1 and G3. (p = 0,4 and p = 0,008 respectively) Patients who needed lymphadenectomy had significantly higher HE4 level than those who had no indications for this procedure (p = 0,001). Conclusions: HE4 is a useful biomarker in diagnosing endometrial cancer. HE4 is associated with high grade endometrial cancer. It can also serve as an useful preoperative counseling tool to identify patients, who may require pelvic and paraaortic lymphadenectomy.Obecnie obserwuje się wzrost zapadalności na raka endometrium, w szczególności bardziej agresywnych typów tej choroby oraz jej występowanie u coraz młodszych pacjentek. Wprawdzie więcej niż 80% przypadków jest diagnozowanych we wczesnych stadiach zaawansowania, dzięki wczesnych objawom, takim jak nieprawidłowe krwawienia. Jednak pacjentki bezobjawowe, jak również przypadki fałszywie negatywnych wyników histopatologicznych są wyzwaniem diagnostycznym i terapeutycznym. W niniejszej pracy dokonano analizy wartości białka HE4 jako metody uzupełniającej diagnostykę raka endometrium. Materiał i metody: Stężenie markera w surowicy krwi zostało oznaczone u 92 pacjentek z nieprawidłowymi krwawieniami. Opierając się na wyniku badania histopatologicznego zostały podzielone na grupę z niezłośliwymi i złośliwymi zmianami endometrium. Analiza statystyczna została wykonana za pomocą testu Mann-Withney. Wyniki: Różnica stężenia HE4 między zmianami niezłośliwymi endometrium a rakiem była istotna statystycznie (p = 0,000) i wartość odcięcia wyniosła 58,08 pmol/l. Różnica stężenia HE4 w stopniu złośliwości raka endometrium G2 i G3 była istotna statystycznie jak również między G1 a G3 (p= 0,4 i p = 0,008 odpowiednio). Pacjentki, które wymagały limfadenektomii miały istotnie wyższe stężenia HE4 od tych, które nie wymagały takiego postępowania (p = 0,001). Wnioski: HE4 jest użytecznym biomarkerem raka endometrium. Jest związany z niskim stopniem zróżnicowania nowotworu. HE4 może być użyteczne w identyfikacji pacjentek wymagających okołoaortalnej i miednicznej limfadenektomii

Effectiveness of gabapentin pharmacotherapy in chemotherapy-induced peripheral neuropathy

Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a common chemotherapy side effect, but its prevention and treatment remains a challenge. Neurotoxicity may lead to dose limitation or even treatment discontinuation, and therefore potentially affect the efficacy of anticancer treatment and long term outcomes. The practice to administer gabapentin for neuropathy may be applicable, but is limited by insufficient studies. The aim of our study was to assess the presence of chemotherapy-induced peripheral neuropathy in ovarian cancer patients treated with first-line paclitaxel and carboplatin chemotherapy and evaluate the effectiveness of gabapentin in treatment of this condition. Material and methods: 61 ovarian cancer patients treated with first line chemotherapy were included in the study. The first phase of the study was to assess neurological condition of each patient by: neuropathy symptoms scale, McGill’s scale, neurological deficit and quality of life, during the chemotherapy. In the second phase of the study we evaluated the response to gabapentin treatment in a group of patients who developed neuropathy. Results: 78.7% of the patients developed chemotherapy related neuropathy. During the course of chemotherapy these patients experienced significant exacerbation of neuropathy symptoms (p < 0.0001), neuropathic pain (p < 0.0001), neurologic deficit (p < 0.0012) and worsening of quality of life (p < 0.0002). Patients who were qualified to undergo the gabapentin treatment observed improvement in symptoms (p < 0.027), pain (p < 0.027) and neurologic deficit (p < 0.019). Quality of life did not change significantly after gabapentin treatment (p < 0.128). Conclusions: Chemotherapy substantially deteriorates the neurologic condition of the patients and the quality of life. Paclitaxel and carboplatin treated patients may benefit from gabapentin therapy in chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy — diagnosis, evolution and treatment

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent neurologic complications experienced by patients receiving antineoplastic drugs. Involvement of the peripheral nerves may have an important impact on daily activi­ties and lead to severe impairment of the patient’s quality of life (QoL). It seems to be of crucial importance to make a correct and early diagnosis of polyneuropathy and, if possible, spare the patient unnecessary suffering or loss of function. In the preceding article we have presented epidemiology, grading and pathogenesis of the toxic CIPN. The purpose of this article is to review current knowledge of diagnostic techniques, prevention and management strategies in the context of CIPN.

Consequences of gynecological cancer in patients and their partners from the sexual and psychological perspective

The diagnosis of gynecological cancer and the following consequences of the treatment radically change the lives of cancer patients and their partners. Women experience negative consequences in terms of sexual, psychological and social functioning. Surgical treatment may result in a decrease in sexual pleasure and pain during intercourse. Chemotherapy and radiotherapy can cause a loss of libido and negatively affect the capacity to experience pleasure or orgasm. Treatment-related changes may include the occurrence of body image disorders, decreased quality of life as well as depressive and anxiety disorders among patients. Furthermore, a negative influence on the relationship between the affected women and their partners, as well as an adverse effect on the social activity, can be observed. Cancer is not an individual experience. It also affects partners of the sick women in terms of psychological and sexual functioning. This article depicts possible problems encountered by cancer patients and their partners from the psychological and sexual perspective. The emphasis is put on understanding sexuality not only in the context of sexual performance, but also in a wider perspective

The effect of Cicatridina® preparation on changes in the vagina due to radiotherapy treatment of cervical or endometrial cancer. Observational study

The problem of changes in the vagina after cancer treatment is particularly important in case of patients who have been administered radiotherapy. A high percentage of patients suffer from vaginal changes which significantly deteriorate the quality of their life, and previously used methods fail to prevent them. The aim of this study is to assess the effects of Cicatridina® preparation containing hyaluronic acid on changes in the vagina in 130 women aged 30–78 (the average age of 59), treated surgically or with radiation therapy for cervical cancer or endometrial cancerand who were treated with vaginal globules. The control group consisted of 54 women treated with radiotherapy for cervical or endometrial cancer who were administered a traditional vaginal douching. Studies carried out 3 and 6 months after treatment showed that the vaginal discomfort was less common (after 3 months – 41% and 6 months – 38%) in women treated with Cicatridina® as opposed to women using vaginal douching (78% and 76% respectively, statistically significant differences, observed both in patients suffering from cervical cancer and those with ovarian cancer). Occlusion of the vagina in the treatment group was also less common (9% both after 3 and 6 months) compared to the control group (18% after 3 months and 20% after 6 months). Statistically significant differences were observed in the whole treatment group.Problem zmian występujących w obrębie pochwy po leczeniu onkologicznym jest szczególnie istotny u chorych, u których zastosowano radioterapię. U dużego odsetka pacjentek dochodzi do zmian w obrębie pochwy, które w znacznym stopniu pogarszają jakość życia, a stosowane do tej pory metody nie są skuteczne w ich zapobieganiu. Celem prezentowanej pracy jest ocena wpływu preparatu Cicatridina® zawierającego kwas hialuronowy na zmiany w pochwie u 130 kobiet w wieku 30–78 lat (średnio 59 lat) leczonych z powodu raka szyjki macicy i raka endometrium operacyjnie i/lub napromienianiem, u których stosowano dopochwowo globulki. Grupę kontrolną stanowiły 54 kobiety leczone napromienianiem z powodu raka szyjki macicy lub endometrium, u których zastosowano klasyczne irygacje pochwy. Badania po 3 i 6 miesiącach od zakończenia leczenia wykazały, że dyskomfort w pochwie występuje rzadziej (po 3 miesiącach – 41% i 6 miesiącach – 38%) u kobiet leczonych Cicatridiną® w porównaniu ze stosującymi irygacje pochwy (odpowiednio 78% i 76%, różnice istotne statystycznie, obserwowane zarówno w grupie pacjentek z rakiem szyjki, jak i w grupie chorych z rakiem jajnika). Zarastanie pochwy w grupie badanej występowało również rzadziej (9% zarówno po 3, jak i po 6 miesiącach) w porównaniu z grupą kontrolną (18% po 3 miesiącach i 20% po 6 miesiącach). Różnice istotne statystycznie zaobserwowano w całej grupie badanej

Expression of BARD1 β Isoform in Selected Pediatric Tumors

Currently, many new possible biomarkers and mechanisms are being searched and tested to analyse pathobiology of pediatric tumours for the development of new treatments. One such candidate molecular factor is BARD1 (BRCA1 Associated RING Domain 1)—a tumour-suppressing gene involved in cell cycle control and genome stability, engaged in several types of adult-type tumours. The data on BARD1 significance in childhood cancer is limited. This study determines the expression level of BARD1 and its isoform beta (β) in three different histogenetic groups of pediatric cancer—neuroblastic tumours, and for the first time in chosen germ cell tumours (GCT), and rhabdomyosarcoma (RMS), using the qPCR method. We found higher expression of beta isoform in tumour compared to healthy tissue with no such changes concerning BARD1 full-length. Additionally, differences in expression of BARD1 β between histological types of neuroblastic tumours were observed, with higher levels in ganglioneuroblastoma and ganglioneuroma. Furthermore, a higher expression of BARD1 β characterized yolk sac tumours (GCT type) and RMS when comparing with non-neoplastic tissue. These tumours also showed a high expression of the TERT (Telomerase Reverse Transcriptase) gene. In two RMS cases we found deep decrease of BARD1 β in post-chemotherapy samples. This work supports the oncogenicity of the beta isoform in pediatric tumours, as well as demonstrates the differences in its expression depending on the histological type of neoplasm, and the level of maturation in neuroblastic tumours

Cancer Stem Cell Markers—Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis

Cancer stem cells (CSCs) may contribute to an increased risk of recurrence in ovarian cancer (OC). Further research is needed to identify associations between CSC markers and OC patients’ clinical outcomes with greater certainty. If they prove to be correct, in the future, the CSC markers can be used to help predict survival and indicate new therapeutic targets. This study aimed to determine the CSC markers at mRNA and protein levels and their association with clinical presentation, outcome, and risk of recurrence in HGSOC (High-Grade Serous Ovarian Cancer). TCGA (The Cancer Genome Atlas) database with 558 ovarian cancer tumor samples was used for the evaluation of 13 CSC markers (ALDH1A1, CD44, EPCAM, KIT, LGR5, NES, NOTCH3, POU5F1, PROM1, PTTG1, ROR1, SOX9, and THY1). Data on mRNA and protein levels assessed by microarray and mass spectrometry were retrieved from TCGA. Models to predict chemotherapy response and survival were built using multiple variables, including epidemiological data, expression levels, and machine learning methodology. ALDH1A1 and LGR5 mRNA expressions indicated a higher platinum sensitivity (p = 3.50 × 10−3; p = 0.01, respectively). POU5F1 mRNA expression marked platinum-resistant tumors (p = 9.43 × 10−3). CD44 and EPCAM mRNA expression correlated with longer overall survival (OS) (p = 0.043; p = 0.039, respectively). THY1 mRNA and protein levels were associated with worse OS (p = 0.019; p = 0.015, respectively). Disease-free survival (DFS) was positively affected by EPCAM (p = 0.004), LGR5 (p = 0.018), and CD44 (p = 0.012). In the multivariate model based on CSC marker expression, the high-risk group had 9.1 months longer median overall survival than the low-risk group (p < 0.001). ALDH1A1, CD44, EPCAM, LGR5, POU5F1, and THY1 levels in OC may be used as prognostic factors for the primary outcome and help predict the treatment response

Targeted sequencing of cancer-related genes reveals a recurrent TOP2A variant which affects DNA binding and coincides with global transcriptional changes in glioblastoma

High-grade gliomas are aggressive, deadly primary brain tumors. Median survival of patients with glioblastoma (GBM, WHO grade 4) is 14 months and \u3c10% of patients survive 2 years. Despite improved surgical strategies and forceful radiotherapy and chemotherapy, the prognosis of GBM patients is poor and did not improve over decades. We performed targeted next-generation sequencing with a custom panel of 664 cancer- and epigenetics-related genes, and searched for somatic and germline variants in 180 gliomas of different WHO grades. Herein, we focus on 135 GBM IDH-wild type samples. In parallel, mRNA sequencing was accomplished to detect transcriptomic abnormalities. We present the genomic alterations in high-grade gliomas and the associated transcriptomic patterns. Computational analyses and biochemical assays showed the influence of TOP2A variants on enzyme activities. In 4/135 IDH-wild type GBMs we found a novel, recurrent mutation in the TOP2A gene encoding topoisomerase 2A (allele frequency [AF] = 0.03, 4/135 samples). Biochemical assays with recombinant, wild type (WT) and variant proteins demonstrated stronger DNA binding and relaxation activity of the variant protein. GBM patients carrying the altered TOP2A had shorter overall survival (median OS 150 vs 500 days, P = .0018). In the GBMs with the TOP2A variant we found transcriptomic alterations consistent with splicing dysregulation. luA novel, recurrent TOP2A mutation, which was found exclusively in four GBMs, results in the TOP2A E948Q variant with altered DNA binding and relaxation activities. The deleterious TOP2A mutation resulting in transcription deregulation in GBMs may contribute to disease pathology