Jatrogeninės menopauzės prevencijos ir vaisingumo išsaugojimo būdai moterims, sergančioms kolorektaliniu vėžiu

Introduction In the last 30 years it was identified an increased incidence of colorectal cancer in young woman. Those women who de­velop rectal cancer may necessitate use of chemotherapy and radiation therapy in combination. For this reason many young women face infertility and iatrogenic premature ovarian failure problems. They are not regularly informed about the risks of chemoradiotherapy on their reproductive system and the possibilities of fertility preservation and restoring ovarian function. So our aim is to introduce the Lithuanian society and our patients with fertility preservation possibility while treating rectal cancer, using ovarian transposition and ovarian tissue cryopreservation. Case report 27-year-old woman was diagnosed with rectal cancer in 2015.10.12. III clinical stage of rectal cancer was found using endo­scopic and radiological tests. Multidisciplinary team discussed this case and decided to begin the treatment with neoadju­vant chemotherapy and radiotherapy after laparoscopic ovarian transposition and ovarian tissue cryopreservation, which was done in 2015.11.25. After that patient was treated with pre-operative chemoradiotherapy. On 2016.02.25 total mesorec­tal excision was removed and patient was set for adjuvant chemotherapy treatment. At the moment, patient‘s treatment is in motion. Conclusions By using combined fertility preservation techniques – ovarian transposition and ovarian tissue cryopreservation – we were able to offer the patient a possibility to avoid iatrogenic premature ovarian failure problems and preservation of ovarian function.ĮžangaPer pastaruosius 30 metų vis daugiau jaunų moterų suserga kolorektaliniu vėžiu. Tokioms pacientėms, nustačius didesnę nei pirmą tiesiosios žarnos vėžio stadiją, dažniausiai pasirenkamas kompleksinis gydymo metodas: derinamas chemospindulinis ir chirurginis gydymas. Todėl dauguma jauno amžiaus moterų po vėžio gydymo susiduria su nevaisingumo ir jatrogeninės ankstyvos menopauzės problema. Pacientės nepakankamai informuojamos apie neigiamą chemoterapijos ir radioterapijos poveikį reprodukcinei sistemai bei galimybes išsaugoti pakankamą reprodukcinės sistemos veiklą ir normalizuoti kiaušidžių funkciją po gydymo. Aprašome klinikinį atvejį norėdami supažindinti Lietuvos gydytojų visuomenę ir pacientus su vaisingumo ir kiaušidžių funkcijos išsaugojimo galimybe gydant tiesiosios žarnos vėžį – atliekant kiaušidžių transpoziciją bei kiaušidžių audinio krioprezervaciją.Klinikinis atvejis27 metų pacientei 2015 m. spalio 12 d. buvo diagnozuotas tiesiosios žarnos vėžys. Endoskopiniais ir radiologiniais tyrimais buvo nustatyta III klinikinė stadija. Daugiadalykio aptarimo metu buvo nutarta gydymą pradėti nuo priešoperacinės chemospindulinės terapijos, prieš tai atlikus laterokolinę kiaušidžių transpoziciją ir kiaušidžių audinio krioprezervaciją, kuri buvo atlikta 2015 m. lapkričio 25 d. Paskui pacientei buvo paskirtas priešoperacinis chemospindulinis gydymas. Jį baigus, konstatuotas patenkinamas terapinis efektas ir 2016 m. vasario 25 d. buvo atlikta laparoskopinė tiesiosios žarnos rezekcija. Navikas pašalintas radikaliai. Šiuo metu tęsiama adjuvantinė chemoterapija.IšvadosNaudojant kiaušidžių transpozicijos ir kiaušidės audinio krioprezervacijos metodus pacientei buvo suteikta galimybė išvengti gydymo sukeltos (jatrogeninės) ankstyvos menopauzės bei tikėtinai išsaugoti vaisingumo funkciją

Slow-Freezing Cryopreservation Ensures High Ovarian Tissue Quality Followed by In Vivo and In Vitro Methods and Is Safe for Fertility Preservation

Background and objectives: Cancer incidence is growing with younger patients diagnosed with this disease every year. Improved cancer diagnostics and treatment lead to better survival of cancer patients. However, after aggressive chemo- or radiotherapy, cancer survivors suffer from various degrees of subfertility or infertility. Several fertility preservation technologies have been developed for young cancer patients: cryopreservation of germ cells, embryos, or reproductive tissues. The best results have been shown by cryopreservation of sperm and embryos. Yet the success of using cryopreserved oocytes or reproductive tissues (ovarian and testicular) is still insufficient. Therefore, this study was designed to assess the vitality, viability, general quality, and safety of frozen–thawed human ovarian tissue for retransplantation using modern molecular tests. Materials and Methods: The new miRNA array test was used to evaluate miRNA expression in thawed ovarian tissue in combination with standard xenotransplantation and pathological examination of microslides. Results: Our results demonstrated that slow freezing is an efficient way (80%) to cryopreserve ovarian tissue with no structural damage afterwards. We have shown that xenotransplantation into immunodeficient mice, histology, and immunohistochemistry could be potentially replaced by more recent molecular methods. Conclusions: The latter method has shown that altered expression of miRNAs might be used as identifiers of normal/damaged tissue after further analysis. Newer, safer, and more specific approaches need to be developed in order to eliminate the risk of disease reoccurrence

Human Papillomavirus and Infertility

Background and objectives. Human papillomavirus (HPV) is the most commonly sexually transmitted infection. Recent evidence suggests that an HPV infection may affect fertility. The aim of the study was to determine the prevalence of HPV infections among couples undergoing in vitro fertilization (IVF) and to identify their awareness of HPV. Material and Methods. A total of 200 samples were collected from couples who received IVF treatment during 2017–2018 in Vilnius University Hospital Santaros Klinikos (VUH SK) Santaros Fertility Centre (SFC). For HPV detection, cervical swabs from women and sperm samples from men were taken and a real time polymerase chain reaction (RT-PCR) was used for the identification of 14 high-risk HPV types. Sperm parameters were evaluated according to World Health Organization (WHO) recommendations for 2010. Research subjects answered an anonymous questionnaire to ascertain their knowledge of HPV. Results. After testing of HPV in couples undergoing IVF, it was found that 33 out of 100 couples (33%) were HPV positive. Of these, 19% of women (19/100) and 20% of men (20/100) tested positive. Using Fisher’s exact test, a statistically significant difference was found between HPV infections and abnormal sperm quality parameters (p = 0.023). Conclusions. HPV may have an impact in spermatogenesis, because an HPV infection was more frequently detected in men with abnormal sperm parameters. High-risk HPV 52 was the most common genotype among couples undergoing IVF treatment

Combined Effect of HPV and Several Gene SNPs in Laryngeal Cancer

Background and objectives: Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck tumors. The molecular mechanism of LSCC remains unclear. The aim of this study was to evaluate the prevalence of Human papillomavirus (HPV) and single nucleotide polymorphisms (SNPs) of TP53, MDM2, MDM4, MTHFR, CASP8, and CCR5 genes in LSCC, and to assess their correlations with patient survival. Materials and Methods: 49 LSCC patients were enrolled in this study. PCR and qRT-PCR were used to detect, identify, and quantify HPV. SNPs were genotyped using PCR and PCR-RFLP. Results: By analyzing the interactions of the SNPs of the genes with clinical parameters, the majority of patients with lymph node status (N1,2) were identified as carriers of MDM2 T/G, CASP8 ins/del, CCR5 wt/wt SNP. Cluster analysis showed that patients with MDM2 T/T SNP survive longer than patients identified as CASP8 ins/ins, MTHFR C/C, and MDM4 A/A variant carriers; meanwhile, LSCC patients with MDM2 T/T polymorphic variant had the best survival. Multivariate analysis showed that HPV-positive patients without metastasis in regional lymph nodes (N0) and harboring CASP8 ins/del variant had the best survival. Meanwhile, HPV-negative patients with identified metastasis in lymph nodes (N1 and N2) and CASP8 ins/del variant had poor survival. Conclusions: This finding suggests patients survival prognosis and tumor behavior are different according HPV status, SNP variants, and clinical characteristics of the LSCC

Investigation of human papillomavirus, its types and variants

Cervical cancer is one of the most common cancers in Lithuania. It is the fourth cancer in women according to the morbidity. The incidence rate of cervical cancer has been increasing in Lithuania since 1992. One of the important risk factor for cervical cancer is human papillomavirus (HPV) infection. The aim of this study is to compare the prevalence of human papillomavirus among cervical cancer patients and women with cervical intraepithelial lesions and healthy women, to determine its types and HPV 16 variants. Polymerase chain reaction and DNA sequencing were used for analysis of specimens taken from cervix uteri. Human papillomavirus was detected in 92.7% of cervical cancer patients and in 26.7% of control women (p<0.0001). It is important to notice that prevalence of HPV in women with high-grade squamous intraepithelial lesions was higher than in the control group. HPV 16 (55.8% in squamous cell carcinoma patients and 35.3% in cervical adenocarcinoma patients) and its European HPV 16 L83V variant were detected more frequently in cervical cancer patients. Studies on HPV, prevalence of its types and variants are very important for HPV based preventive strategies, especially for the vaccination

Expression levels of FBXW7 and MDM2 E3 ubiquitin ligases and their c-Myc and p53 substrates in patients with dysplastic nevi or melanoma

E3 ubiquitin ligases are of interest as drug targets due to their involvement in the regulation of the functions and interactions of several proteins. Various E3 ligase complexes are considered oncogenes or tumor suppres- sors associated with the development of melanoma. These proteins regulate the functions of various signaling pathways and proteins, such as p53 and Notch. The aim of the present study was to determine the expression levels of F-box and WD repeat domain-containing 7 (FBXW7), c-Myc, MDM2 and p53 proteins in samples from patients with dysplastic nevi or melanoma, and to evaluate their association with clinicopathological parameters and prognosis of the disease. Paraffin blocks with postoperative material from 100 patients diagnosed with dysplastic moles or melanoma were used in the present study. Tissue microarrays and immunohistochem- istry were used to examine FBXW7, c-Myc, MDM2 and p53 protein expression. The results revealed that there was significantly lower FBXW7 expression in advanced melanoma compared with dysplastic nevus, melanoma in situ and stage pT1 melanoma (P<0.001). Additionally, there was a statisti- cally significant association between the expression levels of FBXW7 and the morphological type of the tumor (P<0.001). In addition, there was a strong positive association between FBXW7 expression and the changes in c-Myc expression (P<0.02), and a strong trend was observed between decreased FBXW7 expression and a higher risk of death in patients, with the major factor in patient mortality being the stages of melanoma. Additionally, p53 expression was associated with the depth of melanoma invasion and the morphological type of the tumor. In summary, FBXW7 expression exhibited the highest statistically significant prognostic value and associa- tions with advanced melanoma. As the majority of FBXW7 substrates are oncoproteins, their degradation by FBXW7 may highlight these proteins as potential targets for the treatment of melanoma

Distribution of human papillomavirus type 16 variants in Lithuanian women with cervical cancer

Background and objective: Cervical cancer usually is caused by HPV 16. However, HPV 16 varies within type; different genotypes are described as prototype or variants. Prevalence of different variants differ according the geographic regions and has an unequal impact for cervical cancer development. Our study aimed to identify which variant of HPV 16 was most prevalent in biological samples taken from Lithuanian women with cervical cancer. Materials and methods: A total of 122 HPV 16 positive cervical samples (invasive cancer and cervical intraepithelial neoplasia) were investigated and sequenced to identify different variants. HPV 16 was detected using type specific PCR, exact sequence of the virus was obtained by viral DNA sequencing. Results: Adequate HPV sequence was detected in 106 cases from 122 (86.9% of all cases). After histological confirmation, 96 cases were included in the final analysis. In 33 cases (34.4%) HPV 16 prototype was detected; in 50 cases (52.1%), L83V variant; and in remaining 13 cases (13.5%), multivariant of HPV 16. The frequency of L83V variant in invasive cancer and carcinoma in situ samples was the same (66.7% and 62.0%, respectively; P = 0.696). Of analyzed multivariants, 10 were attributed to the European phylogenetic line; 1, to the North American, and 1, to the Asian-American. One sample was not attributed to any of the known phylogenetic lines. Conclusions: The European HPV 16 L83V variant is usually associated with high risk of cervical cancer among women. However, statistically significant difference was not achieved when comparing difference of L83V variants between investigated groups and in HPV 16 L83V variant and prototype distribution in CIN3/Ca in situ and cancer

Žmogaus papilomos viruso paplitimas ir kiti rizikos veiksniai tarp Lietuvos moterų, sergančių gimdos kaklelio vėžiu

Background. Cervical cancer is the second biggest cause of female cancer mortality world-wide and the most common cancer in women in Lithuania. The incidence of cervical cancer is strongly associated with prevalence of HPV. However, not only HPV infection plays a crucial role in cervical cancer development; other risk factors are important which vary in different populations and geographical regions as well as HPV prevalence. The aim of this study was to detect the HPV; its types prevalence and other cervical cancer risk factors for Lithuanian women. Materials and methods. 191 women with primary diagnosed invasive cervical cancer (cases group) and 397 control women were invited to participate in the study. All women were interviewed and samples for HPV testing were taken. Results. In cases group 92.7% of women were infected by HPV, in control group - 26.7% (p < 0.0001). HPV 16 was the most common type in both groups. HPV infection increases the cervical cancer risk 75 times (OR = 75.39; 95% CI 33.61-192.98). Women with lower education, workers, those who started sexual intercourse before 20 years of age, older age of first menstrual period, 3-5 times or more childbirth, smokers and long time or have never had the PAP test had significantly higher risk for cervical cancer development. Other non HPV risk factors were not associated with cervical cancer risk. Conclusions. Data of our study shows the big prevalence of HPV in Lithuanian population. lt may have all impact to biggest cervical cancer incidence. Other risk factors are similar as in other lower economica! resource countries

ŽIV infekuotų nėščiųjų antioksidacinės sistemos būklė.

All pregnant women were compared with non-pregnant women to confirm the influence of pregnancy on the MDA level. In the first trimester, this parameter for pregnant women was close to that of non-pregnant women, while with the developing pregnancy the MDA level increased 1.6 times. No significant difference in the parameter was determined for pregnant women with HPV infection. Conclusions. A decrease of GSH concentration and an increase of MDA level in blood plasma with the development of pregnancy confirmed the presence of a general oxidative stress. The lower levels of GSH and GSH + GSSG in the cervicovaginal washing fluid, if to compare the two trimesters of pregnancy, can be considered as markers of a local oxidative stress. HPV infection depressed the antioxidative system in general and did not affect it at the local level. Systemic oxidative stress, rather than HPV infection, influenced the lipid peroxidation process during pregnancy. The level of MDA is recommended to be tested also during a normal pregnancy, although this parameter should not be considered as an additional biomarker of cervical carcinoma risk. Changes of the antioxidative system variables could induce a deep oxidative imbalance during a pathological pregnancy, and oxidative stress might cause a persistent HPV infection, suggesting the importance of the additional screening of HPV-infected women after delivery