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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.

BACKGROUND/AIM It has been shown in many studies that expression of pyruvate kinase (PK) enzyme plays a key role during cellular metabolism. There is evidence that cancer cells manifesting very dynamic proliferation may control their division in various mechanisms, i.a. by expression of PKM2 isoform. The exact role of PKM2 in ovarian cancer (OC) cells and cancer associated fibroblasts (CAFs) have not been elucidated. MATERIALS AND METHODS The present study was focused on analysis of PKM2 expression in cancer cells and CAFs in 97 OC cases, mostly of serous histological type. Moreover, relationships between expression of PKM2 and proliferation (Ki-67; MCM-2, -3, -7; cyclin D1), vascular (CD31, D2-40) and mesenchymal (Vim and αSMA) markers as well as receptors (ER, PR, HER2, EGFR) were examined. All observations were evaluated in regard to available clinicopathological data. RESULTS The expression of PKM2 was disclosed only in cytoplasm of OC cells. No statistically significant correlation between PKM2 and tested markers was found. In regard to available clinicopathological data only an increasing trend of PKM2 expression with increasing grade of histological malignancy G was found (p=0.07). CONCLUSION Due to achieved results concerning expression of PKM2 there is a lack of evidence for its diagnostic and prognostic usage in OC.

Objectives: Since metformin was reported to decrease overall cancer incidence and mortality and to have antiproliferative and antiinvasive properties, we investigated the impact of metformin intake on survival in endometrial cancer patients. Material and methods: Medical records and survival data of 126 patients with endometrial cancer were analyzed retrospectively. U Mann-Whitney and chi-square tests were applied to compare clinicopathological features. Kaplan Meier model with log-rank test was used to compare survival in the subgroups. Cox proportional hazard model was applied to analyze the relationships between particular factors and overall survival. Results: 107 patients met study criteria and were divided into three groups: 1) patients with type 2 diabetes and metformin users (n=30), 2) patients with type 2 diabetes and metformin non-users (n=38), 3) patients without diabetes mellitus (n=39). No difference in survival between metformin users versus metformin non-users (p=0,86) was observed. Metformin intake, diabetes mellitus co morbidity, plasma glucose level and BMI appeared without influence on survival. When the analysis was restricted to the subgroup of type I endometrial cancer or to endometroid histological type, still neither metformin intake nor diabetes influenced the prognosis. Conclusions: Metformin intake does not alter overall survival in endometrial cancer patients. Diabetes mellitus has no influence on survival in endometrial cancer patients.

Vulvar melanoma is an aggressive neoplasm with a poor prognosis. Approximately 25% to 50% of patients survive 5 years [1]. This malignancy is prone to late metastasis, so 5-year survival does not equal cure. The management of recurrent disease continues to be experimental and individualized [2].

Objectives: The aim of this study was to assess the sensitivity and specificity of HE4 in detecting and differentiating between types I and II epithelial ovarian cancer (EOC) in comparison with CA125. Material and methods: We measured HE4 and CA125 serum concentrations in 206 samples taken from patients operated in Gynecologic Oncology Department due to ovarian tumors. Ovarian cancer was confirmed in 89 cases divided into type I and type II. 52 healthy patients without any gynecological disease formed the control group. The sensitivity and specificity for type I and type II EOC detection and differentiating between both types was evaluated for HE4 and CA125. Results: The HE4 and CA125 serum concentrations were significantly higher in type II than in type I EOC (p=0.008696, p=0.000243 respectively).The HE4 and CA125 sensitivity for type I and benign tumors differentiation was 63.16% for both of them and specificity was 87.29% vs 67.89% respectively. For CA125 these differences did not reach statistical significance. The HE4 sensitivity and specificity for type II and benign tumors differentiation were 87.14% and 96.61%, respectively, and for CA125 these values were 82.86% and 94.07%, respectively. Conclusions: Pretreatment analysis of HE4 serum concentration is superior to CA125 in differential diagnosis of ovarian cancer subtypes (I and II). HE4 is superior to CA125 in detecting ovarian cancer type II. Neither HE4 nor CA125 is an effective diagnostic tool for type I ovarian cancer detection. A new highly specific and highly sensitive tumor marker for type I EOC is needed.

Ovarian cancer (OC) is the leading cause of death among women with genital tract disorders. Melatonin exhibits oncostatic properties which it may effect through binding to its membrane receptor, MT1. The aim of this study was to determine the expression of MT1 in OC cells and to correlate this with clinical and pathological data. Immunohistochemistry was performed on 84 cases of OC. Normal ovarian epithelial (IOSE 364) and OC (SK-OV-3, OVCAR-3) cell lines were used to examine the MT1 expression at protein level using the western blot and immunofluorescence technique. The expression of MT1 was observed as cytoplasmic-membrane (MT1(CM)) and membrane (MT1(M)) reactions. A positive correlation between MT1(CM) and MT1(M) was found in all the studied cases. There were no significant differences between the expression of MT1(CM), MT1(M), and histological type, staging, grading, presence of residual disease, or overall survival time. Immunofluorescence showed both MT1(M) and MT1(CM) expression in all the tested cell lines. Western blot illustrated the highest protein level of MT1 in IOSE 364 and the lowest in the OVCAR-3. The results indicate the limited prognostic significance of MT1 in OC cells.

Objective Evaluation of the long-term HPV-16/18 AS04-adjuvanted vaccine immunogenicity persistence in women. Design Multicentre, open-label, long-term follow-up (NCT00947115) of a primary phase–III study (NCT00196937). Setting Six centres in Germany and Poland. Population 488 healthy women (aged 15–55 years, age-stratified into groups: 15–25, 26–45, and 46–55 years) who received three vaccine doses in the primary study. Methods Immune responses were evaluated in serum and cervicovaginal secretion (CVS) samples 6 years after dose 1. Anti-HPV-16/18 geometric mean titres (GMTs) were measured by enzyme-linked immunosorbent assay (ELISA), and were used to fit the modified power-law and piecewise models, predicting long-term immunogenicity. Serious adverse events (SAEs) were recorded. Main outcome measures Anti-HPV-16/18 seropositivity rates and GMTs 6 years after dose 1. Results At 6 years after dose 1, all women were seropositive for anti-HPV–16 and ≥97% were seropositive for anti-HPV–18 antibodies. GMTs ranged from 277.7 to 1344.6 EU/ml, and from 97.6 to 438.2 EU/ml, for anti-HPV–16 and anti-HPV–18, respectively. In all age groups, GMTs were higher (anti-HPV–16, 9.3–45.1-fold; anti-HPV–18, 4.3–19.4-fold) than levels associated with natural infection (29.8 EU/ml). A strong correlation between serum and CVS anti-HPV-16/18 levels was observed, with correlation coefficients of 0.81–0.96 (anti-HPV–16) and 0.69–0.84 (anti-HPV–18). Exploratory modelling based on the 6–year data predicted vaccine-induced anti-HPV-16/18 levels above natural infection levels for at least 20 years, except for anti-HPV–18 in the older age group (piecewise model). One vaccine-related and two fatal SAEs were reported. Conclusions At 6 years after vaccination, immune responses induced by the HPV-16/18 AS04-adjuvanted vaccine were sustained in all age groups.

The incidence of endometrial cancer (EC) in the population of young women has been increasing. Total hysterectomy with bilateral salpingo-oophorectomy remains the standard therapy for early endometrial cancer [1]. However, doctor and patient attitudes towards radical cancer treatment methods, especially in young women of reproductive age, have been noticeably changing [1–4]. Women expect doctors to apply fertility-sparing therapy, if possible. Early endometrial cancer cases treated with preservation of reproductive function methods have been reported [5]. We present a case of a patient who conceived spontaneously and delivered a healthy newborn after hormonal treatment of early endometrial cancer. A 29-year-old female patient, nullipara, obese (body mass index (BMI) 32.1 kg/m2), presented to her gynecologist with a complaint of irregular, heavy bleeding. For the last year the menstrual pattern was irregular, every 30–60 days, hypermenorrhea lasting up to 14 days. An ultrasound examination revealed endometrial hypertrophy and polyp suspicion. The patient underwent diagnostic dilation and curettage. Histopathology revealed endometrial hyperplasia with atypia with adenocarcinoma foci (Figure 1). Magnetic resonance imaging and chest X-ray excluded more advanced cancer. Treatment options and the risk of cancer progression in case of saving childbearing potential were discussed with the patient, who eventually chose fertility-sparing therapy. She was strongly advised to lose weight with the help of a professional dietician. The patient was treated with high-dose oral progesterone, megestrol acetate 160 mg/day for 6 months after inserting the levonorgestrel intrauterine system (LNG-IUD). Endometrial curettage was performed after removing the levonorgestrel intrauterine system after 6 months. The histopathological examination revealed endometrium with decidual transformation. Mostly the endometrial glands were inactive. Single glands showed signs of hyperplasia without direct atypia. The assessment of atypia was difficult because of the gestagen influence (Figure 2). By that time she had reduced her weight by 30 kg (BMI 22 kg/m2). Then she was given estrogen-progesterone therapy to determine whether the pathological changes of the endometrium depended on the hormonal cycle. Although giving estrogen after a partial response does not seem to be the correct mode of treatment, we applied this treatment on purpose after the suggestion of the histopathologist. After half a year with the LNG system the endometrium showed a few residual foci of hyperplasia along with marked decidual transformation (Figure 2). We wanted to see if these changes would remain during the normal cycle or be shed during menstruation. Because the patient had an irregular menstruation pattern we gave her estradiol (day 5–25 of cycle) and norethisterone 5 mg (day 15–25 of cycle) for three months as part of the diagnostics. Repeat curettage after this treatment showed similar histopathological status and the residual foci did not progress to adenocarcinoma. Figure 1 Pre-therapy. Endometrial glands with neoplastic transformation (H + E, 100×) Figure 2 Post-therapy with high-dose systemic progesterone and local LNG-IUD for 6 months. Stroma with decidual transformation (drug-induced). Hyperplasia within the glandular tubes and on the endometrium surface – foci of residual hyperplasia (H + E, ... The patient was advised to conceive without delay. She was administered dydrogesterone 10 mg/day from day 14 until 28 of each cycle. Spontaneous pregnancy was obtained after 6 months and the patient delivered vaginally a full-term healthy female child. The placenta was not examined histopathologically as the patient delivered in another hospital. After the puerperium the levonorgestrel-releasing intrauterine device was inserted again. The patient is under careful surveillance for possible recurrence of disease. A review of the literature shows that hormonal treatment in grade 1 FIGO I adenocarcinoma without myometrial invasion is safe and can be discussed with patients willing to spare their fertility. Proper selection for fertility-preserving therapy requires diagnostic accuracy. Fertility-sparing therapy can be recommended to patients with early-stage, well-differentiated endometrial carcinoma (FIGO stage IA, Grade 1), presenting no ovarian tumors or metastases, no suspected lymph nodes, and no contraindications for endocrine therapy. Aggressive tumors such as papillary serous, clear cell adenocarcinoma, adenosquamous carcinoma and carcinosarcomas are contraindications for conservative management, and patients with these tumor types should be discouraged from attempting conservative treatment with hormones [6]. The current FIGO classification (2009) for endometrial cancer divides stage I into IA and IB, depending on the depth of myometrial invasion (MI). It is not always possible to evaluate it in the material from dilation and curettage (D&C). The best method of assessing the myometrial invasion and extrauterine spread before surgery is contrast-enhanced magnetic resonance imaging (MRI) [7]. The D&C is preferred to endometrial biopsy and seems to comply with the need for thorough evaluation of grade and occult malignancy [6]. Evaluation of the endometrial tissue should determine the lymphovascular space invasion (LVSI), which is considered a risk factor for lymph node metastasis. A literature search revealed that in case of LVSI the incidence of pelvic lymph node involvement grows from 7% to 27% and the 5-year survival rate decreases from 86% to only 61% of patients [8]. The first-line hormonal treatment for early endometrial cancer is medroxyprogesterone acetate (MPA) (dosage 200–800 mg/day) or megestrol acetate (MA) (10–400 mg/day), which inhibit the estrogen receptor and endometrial cell mitosis, promote apoptosis and induce secretory endometrium [9]. Mostly, 6 months of continuous therapy is enough to obtain remission, although there are cases with a 9-month hormonal treatment [10]. Our patient also did not respond completely after 6 months, despite the fact that she received combined therapy: megestrol acetate and the LNG-IUD. We obtained the resolution of adenocarcinoma foci, but the residual foci of atypical hyperplasia were still present. Although it seemed risky, with patient consent and wish and after thorough information, the chosen strategy was to conceive as soon as possible. Only one similar situation has been published. There is a report from a prospective study in which women were encouraged to conceive before the complete response to hormonal treatment. Remission was obtained by means of a low-dose cyclic natural progestin therapy (200 mg/day from day 14–25). The response rate was 57% and 43% of women conceived, of which 8 were in persistent disease or partial response. Another 3 complete responses were obtained after the delivery [11]. In conclusion, the case illustrates the favorable outcome of pregnancy after high-dose systemic and local progesterone therapy in early stage focal adenomatous endometrial carcinoma with atypical hyperplasia. Six months of continuous therapy and 6 months of cyclical progesterone therapy may achieve a good endometrial response for resolution of focal endometrial carcinoma, and this may favor implantation after the risk factors such as obesity have been controlled.

After the discovery of the role human papilloma virus (HPV) plays in the development of cervical cancer we are witnesses to a change in the conception and interpretation of cervical cancer prevention processes. Primary prevention gained a new tool in the form of HPV vaccines. Secondary prevention, i.e. detection of cervical intraepithelial neoplasia (GIN), acquired a new diagnostic method--the HPV test. Studies were initiated in order to determine the usefulness of HPV tests in cervical cancer prevention and screening. They revealed that the DNA HPV test used in screening has higher sensitivity in CIN detection than PAP smear and that HPV-negative patients are better and longer protected against developing cervical cancer in comparison to women with normal PAP smear results. HPV tests also possess a predictive value, which detects women more susceptible to developing cervical cancer in the future. PAP smear does not have a predictive value. Instead, it only detects a presence or an absence of neoplasia at that particular time. These results clearly indicate that the era of classic PAP smear is indeed coming to an end, replaced by a new primary CIN screening tool--HPV test. The entire cervical cancer screening system must therefore be redefined and reorganized.

We present a rare case of 23-year-old patient with metastatic choriocarcinoma that presented life threatening abdominal bleeding from liver metastases shortly after initiation of treatment with chemotherapy and was treated by emergency embolization of the hepatic vessels. Although the bleeding was controlled, the patient succumbed to the disease on the 15th day after admission. Conclusions: Incontrollable hemorrhagic complications are the most common cause of death in choriocarcinoma metastatic patients. Angioembolization is an effective way of ceasing the bleeding and a potentially life saving measure.

Introduction Malignant tumours are rarely diagnosed during pregnancy, and their prevalence range from 2.4% to5.7%. Ovarian cancer is ranked fifth of all types of cancer and second of all genital cancers diagnosed during pregnancy. In most cases, the course of this disease is symptomless, and usually initial diagnose is made during routine ultrasound examinations. Management of ovarian cancer during pregnancy is a great challenge due to the fact that no clear standards of treatment have been developed so far. The objective of this work This work presents three clinical cases of patients suffered from ovarian cancer diagnosed during pregnancy. , a review of the literature, and the possible therapeutic options. Results Three different clinical scenarios in patients with ovarian cancer diagnosed during pregnancy has been presented. In addition we reviewed current diagnostic and therapeutic algorithms in patients with ovarian cancer and co-existing pregnancy was made. Conclusions Approximately 5% of diagnosed ovarian tumours are malignant. There are no treatment standards in the case of ovarian cancer during pregnancy. Both surgical treatment and the subsequent chemotherapy in the 2nd trimester of pregnancy appear to be safe for the mother and the child. However, the potential risks and benefits associated with the treatment have to be thoroughly analysed on a case-by-case basis, to establish diagnostic and treatment algorithms optimal for every patient.

The HPV-16/18 AS04-adjuvanted vaccine (Cervarix®, GlaxoSmithKline Biologicals) has been shown to induce a robust immune response in women aged 15–55 years (103514/NCT00196937). This follow-up study is the first report of persistence of immune response and safety profile through 48 months after vaccination in women aged 15–55 years. In this open-label, age-stratified Phase III study in Germany and Poland (105882/NCT00196937), healthy women aged 15–55 years received 3 doses of HPV-16/18 AS04-adjuvanted vaccine at 0, 1 and 6 months. Anti-HPV-16/18 seropositivity rates and geometric mean antibody titers (GMTs) were assessed by enzyme-linked immunosorbent assay (ELISA) in women aged 15–25 (n = 168), 26–45 (n = 186) and 46–55 years (n = 177) from the time of first vaccination through 48 months. At Month 48, all subjects were seropositive for anti-HPV-16 antibodies and 99.4% were seropositive for anti-HPV-18. Antibody kinetics were as previously reported, with peak response at Month 7 followed by a gradual decline tending towards a plateau in all age groups. Anti-HPV-16/18 GMTs were sustained at Month 48 in all age groups, including women aged 46–55 years in whom GMTs were respectively 11-fold and 5-fold higher than natural infection levels. The vaccine exhibited a clinically acceptable safety profile in all age groups. In summary, the HPV-16/18 AS04-adjuvanted vaccine induces high and sustained immune responses in women aged 15–55 years, with antibody levels remaining several-fold higher than natural infection levels for at least 4 years after the first vaccine dose.

Estrogen as a potential factor of ovarian carcinogenesis, acts via two nuclear receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), but the cellular signal pathways involved are not completely clear so far. In this study we have described the expression of ERα, detected by immunocytochemistry in 11 ovarian carcinoma cell lines and by immunohistochemistry in 43 Federation Internationale des Gyneacologistes et Obstetristes stage III ovarian carcinoma specimens prepared before and after treatment with cisplatin-based schemes. For cisplatin resistance is a major obstacle in the treatment of ovarian carcinoma, analysis of cisplatin sensitivity in 11 ovarian carcinoma cell line was also performed. The strong nuclear ERα expression was only shown in the single A2780P cell line. Expression of ERα in tissue specimens did not reveal any correlations between histopathological parameters (histologic type and grading). We demonstrated a significant association with ERα expression in specimens from primary laparotomies (PL) and cause–specific survival. In the cases terminated by death of the patient, overall immunoreactivity score of ERα expression at PL was significantly lower than in surviving patients. In addition, Kaplan-Meier analysis revealed significantly shorter overall survival time and progression-free time in cases with lower immunoreactivity score of ERα expression at PL. Our findings support the hypothesis that aberrant hormone activity, by way of altered receptor expression, might be an important factor in the malignant transformation of ovarian cancer.

Toll-like receptors (TLRs) expressed on immune cells trigger inflammatory responses. TLRs are also expressed on ovarian cancer (OvCa) cells, but the consequences of signaling by the TLR4/MyD88 pathway in these cells are unclear. Here, TLR4 and MyD88 expression in OvCa tissues (n=20) and cell lines (OVCAR3, SKOV3, AD10, A2780 and CP70) was evaluated by reverse transcriptase-PCR, western blots and immunohistochemistry. Cell growth, apoptosis, nuclear factor-kappaB (NF-kappaB) translocation, IRAK4 and TRIF expression and cJun phosphorylation were measured following tumor cell exposure to the TLR4 ligands, lipopolysaccharide (LPS) or paclitaxel (PTX). Culture supernatants were tested for cytokine levels. TLR4 was expressed in all tumors, tumor cell lines and normal epithelium. MyD88 was detectable in tumor tissues and in 3/5 OvCa lines but not in normal cells. In MyD88(+) SCOV3 cells, LPS or PTX binding to TLR4 induced IRAK4 activation and cJun phosphorylation, activated the NF-kappaB pathway and promoted interleukin (IL)-8, IL-6, vascular endothelial growth factor and monocyte chemotactic protein-1 production and resistance to drug-induced apoptosis. Silencing of TLR4 in SCOV3 cells with small interference RNA resulted in phosphorylated-cJun (p-cJun) downregulation and a loss of PTX resistance. In PTX-sensitive, MyD88(neg) A2780 cells, TLR4 stimulation upregulated TRIF, and TLR4 silencing eliminated this effect. Thus, TLR4/MyD88 signaling supports OvCa progression and chemoresistance, promoting immune escape.

Objective To assign cutoff values for human chorionic gonadotropin (β-hCG) in pretreatment and after one methotrexate (MTX) cycle and determine its correspondence to the number of MTX cycles in successfully treated ectopic pregnancy. Design Retrospective study. Setting Polish university hospital. Patient(s) 68 women with ectopic pregnancies who qualified for medical treatment. Intervention(s) A single-dose of MTX (50 mg/m 2 ) repeated every 7 days, plus laparoscopy in cases of tubal rupture or increased (≥50% over 1 week) β-hCG concentration. Main Outcome Measure(s) Resolution of serum β-hCG without the necessity of laparoscopy. Result(s) Success rate was 78% (53 of 64 women). The medians of pretreatment β-hCG levels in the groups treated successfully and unsuccessfully (943 vs. 3085 mIU/mL) and after the first dose of MTX (564 vs. 4049 mIU/mL) were statistically significantly different. The decrease in β-hCG level after one MTX dose differed statistically significantly only in successfully treated women. The receiver operating characteristic (ROC) curve cutoff value in the success group indicated an initial β-hCG level of 1790 and 1218 mIU/mL after one MTX cycle. The median of β-hCG titer was not statistically different in patients requiring one or more treatment cycles. Conclusion(s) When the β-hCG level is >1790 mIU/mL, the MTX treatment of ectopic pregnancy is at risk of failure. However, the initial β-hCG titer is not a predictor of the number of MTX cycles that can guarantee a successful outcome.

After the discovery of the role human papilloma virus (HPV) plays in the development of cervical cancer we are witnesses to a change in the conception and interpretation of cervical cancer prevention processes. Primary prevention gained a new tool in the form of HPV vaccines. Secondary prevention, i.e. detection of cervical intraepithelial neoplasia (GIN), acquired a new diagnostic method--the HPV test. Studies were initiated in order to determine the usefulness of HPV tests in cervical cancer prevention and screening. They revealed that the DNA HPV test used in screening has higher sensitivity in CIN detection than PAP smear and that HPV-negative patients are better and longer protected against developing cervical cancer in comparison to women with normal PAP smear results. HPV tests also possess a predictive value, which detects women more susceptible to developing cervical cancer in the future. PAP smear does not have a predictive value. Instead, it only detects a presence or an absence of neoplasia at that particular time. These results clearly indicate that the era of classic PAP smear is indeed coming to an end, replaced by a new primary CIN screening tool--HPV test. The entire cervical cancer screening system must therefore be redefined and reorganized.

Resistance to cis- or carboplatin represents the principal cause of therapeutic failures in ovarian carcinoma. The phenomenon of resistance to platinum-based drugs is partly related to expression of metallothionein (MT) and of glutathione S-transferase pi (GST-pi), but opinion on the subject is discordant. Documentation of a negative predictive effect of MT and GST-pi expression for the therapy employing platinum-based drugs would permit to select resistant cases in which other therapeutic approaches could be employed. The present study aimed at examining the relation between intensities of MT and GST-pi expressions in ovarian carcinomas and dynamics of the clinical course in the neoplastic disease in a group of cisplatin-treated patients. The analyses were performed on samples of ovarian carcinoma originating from 43 first-look laparotomies (FLLs) and, in 30 cases, from second-look laparotomies (SLL) from the same patients. Immunohistochemical reactions were performed on paraffin sections of studied tumors, using monoclonal antibodies to MT and GST-pi. The calculations showed that in cases with augmented expression of MT, mortality was higher. On the other hand, augmented expression of GST-pi predisposed to more frequent relapses, deaths and progression of the tumor. Kaplan-Meier analysis showed that a significantly shorter survival time was linked to cases of higher expression of MT at FLL and of higher expression of GST-pi at FLL, whereas a shorter progression-free time was manifested by cases with higher expression of GST-pi at FLL. The performed investigations indicate that augmented expressions of MT at FLL and GST-pi at FLL in ovarian cancer represent an unfavourable predictive factor in cisplatin-treated patients.

Among many alterations within the TP53 gene the rs1042522 (C72G, p.Pro72Arg) has been associated with numerous cancers , however the results differ between populations for opposite Pro or Arg alleles. Similar thus inconclusive results are observed in ovarian cancer, which may suggest that the rs1042522 does not influence ovarian carcinogenesis directly, but might be linked to another pathogenic alteration. WRAP53 which overlaps the TP53 is required to maintain normal levels of p53 upon DNA damage, but also when altered may independently increase the risk of cancer. To evaluate the association between three SNPs located in WRAP53-TP53 region: rs1042522, rs2287497, rs2287498 and ovarian cancer risk in Polish population we genotyped 626 cases and 1,045 healthy controls. Our results provide the evidence for an association between studied SNPs and a risk of invasive ovarian cancer in Poland. We found that CC homozygotes in rs1042522 were more frequent in cancers when compared to controls (OR = 1.46, p = 0.03). Similarly in WRAP53 both TT homozygotes in rs2287497 (OR = 1.95, p = 0.03) and AA homozygotes in rs2287498 (OR = 2.65, p = 0,01) were more frequent among cases than healthy individuals. There is also a suggestive evidence that specific homozygosity of studied SNPs in TP53-WRAP53 region is significantly overrepresented in ovarian cancer patients. In conclusion SNPs in WRAP53 (rs2287497 and rs2287498) have stronger association with an ovarian cancer risk than rs1042522 in TP53.

Objective: Numerous studies suggest that cyclooxygenase-2 (COX-2) is overexpressed in cancer. Our objective was to investigate the relationship between COX-2 expression in ovarian carcinoma and clinicopathological factors. An emphasis was put on the association with the new pattern of tumorigenesis that divides tumors into type I – less aggressive, and type II – more aggressive one. The prognostic significance of COX-2 expression was evaluated. Methods: Ovarian cancer tissues were obtained from 65 patients in FIGO III stage (23 with type I and 42 with type II ovarian cancer). COX-2 expression was evaluated by immunohistochemistry. The statistical analysis was performed in order to assess the connection between COX-2 expression and characteristic factors of ovarian cancer patients as well as the new division for type I and type II ovarian cancer. Results: COX-2 expression was detected in 91% of tissue samples. It was markedly elevated in well differentiated tumors (p=0.0041). The platinum - resistant tumors had significantly higher expression of COX-2 (p=0.0337). There was no difference between COX-2 expression in type I and type II ovarian cancer (p=0.6720). The COX-2 staining was not associated to age, CA125 level, the presence of ascites or any special histological type. An increased expression of COX-2 was an unfavorable prognostic factor for overall survival (p=0.0369) and progression-free survival (p=0.0218). Multivariate analysis confirmed that COX-2 overexpression is an independent unfavorable prognostic factor of shorter progression-free survival (p=0.048). Conclusions: COX-2 expression is an unfavorable prognostic factor for progression-free survival and overall survival in ovarian cancer. There is no relationship between COX-2 expression in ovarian cancer tissue and the examined model of ovarian cancer pathogenesis.

We present a review of the current implementation status of vaccination against human papillomaviruses (HPV) and available data concerning the burden of HPV infection and HPV type-specific distribution in 16 central and eastern European countries: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, the Czech Republic, Estonia, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia, and The Former Yugoslav Republic of Macedonia. At least one current HPV prophylactic vaccine is registered in all central and eastern European countries except Montenegro. Six counties-Bulgaria, the Czech Republic, Latvia, Romania, Slovenia, and Former Yugoslav Republic of Macedonia-have integrated the HPV vaccination into their national immunization program and currently provide routine vaccination free of charge to the primary target population. Ten countries have not integrated HPV vaccination into the national immunization program. The key reasons for lack of implementation of HPV vaccination into the national immunization program are the high vaccine cost and negative public perception. Vaccination of males is not recommended in any country in the region.

Background: In patients with Ovarian Cancer (OvCa) exosomes released by tumor cells are present in the plasma and could be involved in tumor progression. This study examines the association between the exosome presence/protein content in plasma of OvCa patients and disease outcome, response to standard therapy and/or tumorresistance to therapies in patients studied at diagnosis and also serially during and after therapy. Design and methods: Exosomes were purified from OvCa patients’ plasma (n=22), patients with benign tumors (n=10) or (n=10) healthy controls (NC) using ultracentrifugation. Exosomes were visualized by scanning electron microscopy. Their protein content was measured. The presence of MAGE 3/6 and TGF-β1 in exosomes was evaluated in Western blots. Results: The OvCa patients’ plasma contained higher levels of exosomal proteins (p

The Polish Gynecological Society is an organization that assembles a part of Polish gynecologists working at different institutions and positions. The primary goal of this entire group of professionals should be the care for the health and wellbeing of their patients--women at different stages of their life. Many activities that promote the improvement of population health result from good understanding of health problems of the Polish population and are implemented by means of ordinances, acts and prophylactic programs but fail due to poor response resulting from lack of knowledge and proper preparation. Unsatisfactory effects of prophylactic activities are connected with low level of education. Types of scientific publications in "Polish Gynecology" are mainly dependent on the magazine profile. There are no limitations that would constitute a source of rejection of articles that deal with public health problems. In fact, the subject of many articles published in "Polish Gynecology" pertains to the problems of procreative health. Proper attitude and desire to live healthy might influence the course of pregnancy and neonate wellbeing. Women planning pregnancy as well as the pregnant ones, should be made aware of that. General practitioners, obstetricians and pediatricians, like other doctors registered at the Polish Medical Council, receive both regional and national magazines published by Medical Councils and this way of reaching them seems to be the easiest.

Comparison of conventional cytodiagnostics with molecular identification of DNA and mRNA HPV HR, immunocytochemical test for suppressor protein P16 and nuclear Ki 67 to detect cervical pathology screening of the division to LG SIL and HG SIL.630 Pap smears were taken from women with suspected cervical pathology were submitted for analysis, together with 558 smears for the presence of DNA HPV HR, 421 swabs for the presence of mRNA HPV HR, 86 swabs for the presence of suppressor protein P16 and nuclear Ki 67. In all of the women standard colposcopy with biopsy and endocervical abrasion were performed.The study used a classic cytological smear taken on the slide, rated in accordance with TBS classification, colposcopy implemented in accordance with the guidelines of the International Federation of Cervical Pathology and Colposcopy from 2003, molecular diagnostic tests based on identifying DNA, mRNA HPV HR and immunocytochemistry diagnostic test--CINtecPLUS.The sensitivity of Pap test identification of CIN 2+ was of 85% and specificity of 23%. Indicators PPV and NPV were respectively 39% and 72%. The accuracy of cytology reached a level of 46%. DNA HPV HR test obtained 91% sensitivity and 33% specificity of the diagnosis of CIN 2+. Its accuracy was 54%. The value of PPV and NPV for molecular diagnostics was respectively 43% and 87%. For mRNA HPV HR test sensitivity of the method was 79%, the specificity was 67%. CINTecPLUS test achieved 100% sensitivity and 67% specificity in the diagnosis of CIN 2+.1. Conventional cytodiagnostics are inferior in terms of both sensitivity and specificity of molecular test for DNA, mRNA HPV HR and immunocytochemical test for detecting of LG SIL and HG SIL. 2. Immunocytochemical technique shows maximum sensitivity and high specificity of detection of actual precancerous stages--CIN 2+.

The aim of the study was to assess the diagnostic value of pap smears and detection of the p16 and Ki67 proteins in women with cervical intraepithelial neoplasia (CIN).630 women, aged between 25 and 65, with abnormal pap smears were included into the study All patients had a control pap smear and in each case punch biopsy with endocervical curettage were performed under the control of a colposcope. The presence of p16 and Ki67 proteins was detected using the CINtecPlus test. The results of the research were statistically assessed.Abnormal pap smears were found in 82.5% (520/630) of the studied women. In 40% (252/630) of the cases the LSIL changes were found. The recognition of ASC-US concerned 35.2% (222/630) of the patients, and pap smears with the HSIL result were found in 7.3% (46/630) of the women. In 17.5% (110/630) of the patients the result of the cytological examination was normal. Abnormal results of the pap smears were found significantly statistically more frequently (p0,0001) in women with cervical intraepithelial neoplasia (CIN). The results of the CINtecPlus test were positive in 68,4% of women with CIN and in 33,3% of patients with normal cervix. In the group of women with precancerous lesions (HGSIL/CIN2+) the diagnostic accuracy of the pap smear was 41% for the cytological results ASC-US, 56% LSIL and 73% for detection of HSIL. Immunocytochemical detection of p16 and Ki67 proteins gained the highest accuracy (78%) in recognition of cervical precancerous lesions.1. ASC-US and LSIL cytological recognition has low accuracy in the diagnosis of CIN2+ cervical changes. 2. Cytological recognition of HSIL has the highest accuracy in the diagnosis of CIN2+ changes. 3. Immunocytochemical detection of p16 and Ki67 proteins is more accurate in recognizing precancerous states and cervical cancer than cytological examination. 4. Immunocytochemical detection of the p16 and Ki67 proteins can be used to triage patients with atypical squamous cells of undetermined significance and low grade squamous intraepithelial lesions.

Assessment of frequency of regression and progression of mild cervical neoplasia in women positive for types of HPV DNA of high oncogenic potential.111 women were studied. One-year-long observation of patients included cervical cytology conducted every three months, and colposcopy conducted every six months. After a period of 12 months all women were evaluated with colposcopy and directed biopsies of abnormal cervical tissue.This study confirms the significant effect of age on both regression and progression of low-grade cervical intraepithelial neoplasia.In the age group below 26 years, complete regression of LGSIL occurs significantly more frequently than in older women. Whereas in the over 36 age group, progression to HGSIL occurred more frequently during 12 months of follow-up.

Ovarian cancers (OC) belong to a heterogeneous group of pathologies and are traditionally classified with regard to histological type and degree of differentiation. OC was hypothesized to originate from ovarian surface epithelium (OSE) and inclusion cysts epithelium (IC). Unfortunately this theory was never supported by any clinical or molecular evidence linking carcinogenesis with OSE and was refuted. OC subtypes demonstrate morphologic features that resemble Müllerian duct-derived epithelia of the genital tract. Investigations of the HOX gene family Müllerian epithelial differentiation markers, confirmed the HOX genes expression in many subtypes of OC but not in OSE. The first step towards connecting OC origin with other than OSE genital tract structures were epidemiological observations indicating a minor OC risk after tubal ligation in women with the BRCA mutation. The first in situ carcinoma was found in the Fallopian tube fimbriae. Further research confirmed the same mechanism in sporadic OC. Endometriosis and endometrium cells may be a highly probable place of endometrioid OC initiation. Mucinous types share common futures with gastrointestinal tract cancers and there one needs to search for their precursors. Clear cell carcinoma may arise from glandular epithelium of endocervix or from endometrioid foci. The new classification of OC was proposed in 2004, suggesting to divide all OC into two types: I and II. Type II includes serous and endometrioid G3 subtypes, carcinosarcomas and undifferentiated OC. They are responsible for 75% of OC morbidity identified usually in FIGO stages Ill or IV, have poor prognosis and relapse early The remaining hystiotypes, with better prognosis and earlier FIGO stages at time of diagnosis, were classified as type I. Serous and endometrioid poorly differentiated ovarian cancers demonstrate mutation in TP53 gene (type II) and highly differentiated ones, generally in BRAS and KRAS genes (type I). The differences in molecular pathways also confirm different patterns of carcinogenesis of both OC types. Modern approach to OC histogenesis and origin emphasizes the necessity to verify OC screening, detection and treatment methods.

Circulating tumor cells (CTCs) are cells released from the primary tumor and circulating in peripheral blood. CTCs are an important element in the process of understanding the biology of metastases. In the future CTCs may be used as biomarkers for the assessment of neoplastic process progression and recurrence. The CTCs presence in peripheral blood was described in various tumors, and the possibility of their use in clinical procedures was demonstrated. The appearance of CTCs is a sign of metastasis formation and its spread via the circulatory system. Ovarian cancer is a special type of tumor as it grows and recurs mainly in the abdominal cavity. Despite advances in therapeutic methods, more than half of the patients with ovarian cancer experience disease recurrence which cannot be cured. Therefore, it is important to seek better treatment strategies for patients with advanced disease. There is evidence that CTCs in patients with ovarian cancer may be associated with the appearance of recurrences, disease-free time and total survival time. Detection and molecular analysis of CTCs may also be a non-invasive test for detecting an early stage of the disease, impossible to diagnose using currently available diagnostic tools. Monitoring can also be a prognostic factor enabling the evaluation of the therapeutic response. CTCs detection will contribute to better patient outcomes by using an improved system of diagnosis and monitoring of patient therapy allowing for immediate implementation or change of the treatment when necessary.

Degradation of the extracellular matrix and basement membrane is a critical step in tumor progression. Matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP 2) act in a coordinated manner to form an integrated system involved in ovarian cancer (OC) progression. In this study, the authors describe the expression of TIMP-2 detected by immunohistochemistry in 6 OC cell lines and in 43 malignant epithelial ovarian tumors (in tumor and stromal compartments) in sections originating from primary laparotomies. No significant correlations between overall and progression-free survival and TIMP-2 expression in tumor compartment were observed. The analysis demonstrated a significant association between enhanced stromal expression of TIMP-2 and better clinical response to cisplatin- and paclitaxel-based chemotherapy. Increased expression of TIMP-2 in the stromal compartment and simultaneous overexpression in both stromal and tumor compartments strongly correlated with increased survival. No significant correlations were found in vitro between resistance to cisplatin, paclitaxel, or topotecan and the expression of TIMP-2 in the OC cell lines, suggesting stromal influences on tumor chemoresistance in the physiological environment. This study supports the concept of TIMP-2 expression in the stromal compartment of OC as a promising marker of prognosis and response to cisplatin- and paclitaxel-based chemotherapy in OC patients.

Scientific journals are ranked and evaluated to measure their relative importance and influence on science within a specific field. One of the tools most widely used to evaluate and compare journals is the Thomson Reuters Impact Factor In Poland a specific value of a scientist's Impact Factor is required for academic promotion. Ginekologia Polska was placed on the Master Journal List in 2008 in the result of changes introduced in 2007 by the new Chief Editor prof. Marek Spaczynski. In 2010, first time in its history the journal was listed in the Journal Citation Reports with the Impact Factor 0.367. The analysis of Ginekologia Polska contemporary value, as well as of prospects for its development was conducted on the basis of the Journal Citation Reports. In the light of the JCR data, Ginekologia Polska is a highly regarded title compared to other Polish journals. Its value and importance is gradually growing.

The optoelectronic method is one of the most promising concepts of biophysical program of the diagnostics of CIN and cervical cancer. Objectives of the work are evaluation of sensitivity and specificity of the optoelectronic method in the detection of CIN and cervical cancer. The paper shows correlation between the pNOR number and sensitivity/specificity of the optoelectronic method. The study included 293 patients with abnormal cervical cytology result and the following examinations: examination with the use of the optoelectronic method — Truscreen, colposcopic examination, and histopathologic biopsy.Specificity of the optoelectronic method for LGSIL was estimated at 65.70%, for HGSIL and squamous cell carcinoma of cervix amounted to 90.38%. Specificity of the optoelectronic method used to confirm lack of cervical pathology was estimated at 78.89%.The field under the ROC curve for the optoelectronic method was estimated at 0.88 (95% CI, 0.84–0.92) which shows high diagnostic value of the test in the detection of HGSIL and squamous cell carcinoma.The optoelectronic method is characterised by high usefulness in the detection of CIN, present in the squamous epithelium and squamous cell carcinoma of cervix.

This pooled analysis of data from four Phase III clinical trials was undertaken to assess the correlation between levels of anti-human papillomavirus (HPV)-16/18 antibodies in serum and cervicovaginal secretions (CVS) in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine. Serum and CVS samples were collected from a subset of women aged 10-65 years (N=350) at pre-specified time-points from 7 to 36 months post-vaccination. Anti-HPV-16/18 antibody levels in serum and CVS were measured by enzyme-linked immunosorbent assay. Pearson correlation coefficients between serum and CVS antibody levels, standardized for total immunoglobulin G, were calculated at each time-point in women with detectable antibodies in both serum and CVS. All subjects had seroconverted at Month 7 and remained seropositive through Month 36 for both antigens. Geometric mean titers of anti-HPV-16/18 antibodies in serum were substantially higher at all time-points than those in a control group of women who had cleared a natural HPV infection in another trial. In women with detectable antibodies in both serum and CVS, good correlation was seen between HPV-16/18 antibody levels at all time-points (Pearson correlation coefficient: 0.84-0.92 for HPV-16 and 0.90-0.91 for HPV-18). The strong correlation between levels of HPV-16/18 antibodies in serum and CVS up to 36 months post-vaccination in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine supports transudation of serum antibodies as the mechanism by which antibodies are introduced into CVS. These CVS antibodies may play a role in the protective efficacy of this vaccine.

Screening programs may contribute to decreasing the mortality rate in a given population and their main target, in case of cervical cancer; is to find and to cure preclinical stages of this malignancy. Regularly repeated tests in defined time intervals can diagnose the illness at its early stages but the results come with a high cost. Population program of early detection of cervical cancer has been conducted since 2007 and is run by the Central Coordinating Center and 16 regional centers. Funds for promotional, educational, monitoring and medical activities are obtained from the National Health Service.The aim of this study was to present the cost-effectiveness of the Program between 2007 and 2009.The material for the analysis was obtained from the SIMP system, where all the data about women participating in the Program are implemented. The analysis of the cervical carcinoma treatment and procedure costs was made on the basis of the National Health Service estimates. The number of new cervical carcinoma cases was calculated with the help of the newly introduced system code--C53.Between 2007 and 2009 the cost of one cytological smear was similar in all regions (about 10 PLN). The highest costs were noted in Lubuski and Swietokrzyski regions. The costs of promotional and educational activities amounted up to 4.5 million PLN. A single cervical smear test cost for one woman has increased in the analyzed years from 3.95 up to 7.34 PLN. The total cost of one woman cytological examination--medical and non-medical elements--was more than 60 PLN. In 2009, 622 new cases of cervical cancer were found thanks to the Program. The cost of one case of cervical cancer diagnosis was 15 000 PLN. The total costs of all cases of cervical cancer in 2009 was 45.5 million PLN.The situation calls for creating new and effective tools for monitoring medical, epidemiological and financial parameters of the Program. Otherwise, the estimates of the health and social impact of the Program will fail to be plausible. Increased attendance at the Program will only marginally lower the costs of the tests. Not to mention, that different means and solutions regarding cervical cancer prevention need to be suggested due to the fact that Polish population does not yet seem to have developed the habit of taking preventive tests.

The Impact Factor is a measure of average citation frequency for articles in a specific scientific journal during a specific period of time. IF takes into account the content, sources, layout and frequency and regularity of publishing. In order to get an impact factor, a journal needs to be first put on the Philadelphia List. In 2001, after the change of the Editor-in-Chief, Polish Gynaecology started the process of trying to get an IF The analysis of contemporary value of the publication was done on the basis of the SJR indicator and the Scopus database. It has revealed that, despite a decrease in the number of publications per year, the percentage of citations has risen to 20%, not to mention an increase in the number of references and articles published within international cooperation. The quality of article summaries in English is of great importance and offers a chance to increase the number of citations of the articles, available online at Medline and Pubmed free of charge. Evaluation of the SJR indicator of all Polish gynecological journals gives reason to believe that Polish Gynaecology is a highly regarded and valued publication.

Development of primary prevention of cervical cancer in other words a vaccination against selected, oncogenic HPV types, entails an increasing importance of epidemiological studies and prevalence of various types of human papilloma virus. The incidence of HPV varies depending on the geographic location of the population. The effectiveness of primary prevention against HPV 16, 18, in the context of reducing the incidence of cervical cancer will depend, among others, on the prevalence of these types in the population and virus-like antigens, which are partially cross-resistant.Identification of the most frequent, oncogenic HPV types in women with HG SIL diagnosis from Central and Western Poland to assess the merits of the development of primary prevention.For the purpose of molecular tests identifying the presence of 13 DNA oncogenic virus types, swabs were taken with the cyto-brush from 76 women diagnosed with CIN 2 or CIN 3 (HG SIL). Patients eligible for the study were diagnosed at the Laboratory of Pathophysiology of Uterine Cervix, Gynecology and Obstetrics Clinical Hospital of Karol Marcinkowski University of Medical Sciences. Patients came from Central and Western parts of Poland.Cell material in which the method of Amplicor HPV (Roche Diagnostics) identified the presence of DNA of oncogenic HPV types was in each case subsequently subjected to genotyping using the molecular test - Linear Array HPV Genotyping (Roche Diagnostics).Five most common oncogenic HPV types in order of detection included: 16, 33, 18, 31, 56. Together these five types of virus comprised 75.86% (88/116) of all detected HPV types.1. In women from Central and Western Poland, diagnosed with HG SIL, the most common HPV genotypes were HPV 16, HPV33, HPV 18, HPV31, HPV56. 2. Two HPV types 16 and 18, against which vaccinations are directed, belong to the group of three genotypes of HPV most commonly identified in the evolution of CIN 2, CIN 3 diagnosed in women from Central and Western Poland.