The expression of metallothionein (MT) and proliferation intensity in ovarian cancers treated with cisplatin and paclitaxel

Metallothioneins (MT) represent low molecular weight proteins that are supposed to fulfil several functions. They participate in the cell cycle, protect cells from oxidative stress, control levels of heavy metals and participate in multidrug resistance processes, particularly in cases of alkylating drugs. The present study aimed at evaluation of proliferation intensity (Ki67, PCNA) in ovarian cancers treated using cisplatin and paclitaxel, as related to expression of MT. The experiments were performed on samples originating from 10 patients operated on due to ovarian cancer. The material originated from the first operations or second-look operations. All the patients were treated with cisplatin and paclitaxel. Immunocytochemical reactions using antibodies to MT, Ki67 and PCNA were performed in paraffin sections originating from the cases studied. Statistical analysis was performed using Statistica software. The studies demonstrated no relation between expression of MT on the one hand and intensity of proliferation before or after chemotherapy on the other hand (gamma correlation, p > 0.05). The results indicate that expression of MT is not related to resistance to treatment using cisplatin and paclitaxel

Hypoactive sexual desire disorder

Abstract Sexual dysfunctions in women is a topic that has only just started to appear in scientific publications. Relatively little is known about the extent of the problem, but some reports suggest that sexual dysfunctions are highly prevalent, affecting 20% to even over 40% of all women. Most authors agree that female sexual dysfunctions are age-related. Epidemiological data confirms that fact and shows that one third of women demonstrate lack of interest in sex and nearly one fourth do not achieve orgasm. Approximately 20% of women report difficulties with vaginal lubrication and for 20% sex is not enjoyable. For many of them such problems influence the relationships with their partner in a negative way and are the reason of personal failures and. It should be emphasized that Hypoactive Sexual Desire Disorder is the most prevalent sexual dysfunction in all female age groups. Until 50 years ago, sexual dysfunction was not regarded as a serious medical problem which is directly responsible for scarce or limited clinical data available on the topic nowadays. The mechanisms underlying Hypoactive Sexual Desire Disorder remain elusive and, as a consequence, in most cases there is still no effective treatment. In recent months, reports have been published suggesting that the situation may change soon. The introduction of new diagnostic tools and data from completed clinical trial phases may prove a real breakthrough in the diagnostics and treatment of the hypoactive sexual desire disorder

CZY NADCHODZI ZMIERZCH SKRININGU CYTOLOGICZNEGO?

After the discovery of the role human papilloma virus (HPV) plays in cervical cancer development we have witnessed 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, which is cervical intraepithelial neoplasia (CIN) detection, acquired a new diagnostic method – HPV test. Studies were initiated in order to determine the usefulness of HPV tests in cervical cancer prevention and screening. They revealed that 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; it only detects a presence or absence of neoplasia at this 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 from the ground up.Po odkryciu roli wirusa brodawczaka ludzkiego (HPV) w rozwoju raka szyjki macicy jesteśmy świadkami dużych zmian dokonujących się w koncepcji i interpretacji procesu profilaktyki raka szyjki macicy. Profilaktyka pierwotna zyskała nowe narzędzie prewencji jakim są szczepionki przeciwwirusowe. W profilaktyce wtórnej, czyli wykrywaniu śródnabłonkowej neoplazji (CIN) pojawiła się nowa metoda diagnostyczna – test HPV. W krótkim czasie zainicjowano badania, które miały określić przydatność testowania HPV w profilaktyce i w skriningu raka szyjki macicy. Wykazano, że test DNA HPV użyty w skriningu ma większą czułość w wykrywaniu CIN w porównaniu do testu cytologicznego (PAP) a kobiety HPV ujemne są lepiej i dłużej chronione przed zachorowaniem na raka szyjki macicy w porównaniu do kobiet z prawidłowym wynikiem PAP. Testy HPV mają także wartość predykcyjną, czyli wskazują, które kobiety są w grupie wysokiego ryzyka rozwoju raka szyjki macicy w przyszłości. Test cytologiczny nie ma wartości predykcyjnej, wskazuje tylko stan faktyczny w momencie jego wykonania. Wyniki te jednoznacznie wskazują, że era klasycznej cytologii raczej dobiega końca i będzie ona pełnić rolę drugorzędną w stosunku do testów HPV. Cały system badań przesiewowych w kierunku raka szyjki macicy musi zostać na nowo zdefiniowany i zorganizowany

Czy metformina pomaga pacjentkom z rakiem endometrium?

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.Cel pracy: Wobec doniesień o korzystnym działaniu metforminy polegającym na zmniejszaniu zapadalności i umieralności na choroby nowotworowe oraz o jej właściwościach antyproliferacyjnych i hamujących naciekanie, w tej pracy postanowiliśmy zbadać wpływ metforminy na przeżycie pacjentek z rakiem endometrium. Materiał i metody: Retrospektywnej analizie poddane zostały historie chorób 126 pacjentek z rakiem endometrium. Cechy histopatologiczne porównano przy użyciu testów U Mann-Whitney i chi-kwadrat, a przeżycie pacjentek w podgrupach za pomocą estymatora Kaplana Meiera (test log-rank). Model Coxa zastosowano, żeby określić zależności pomiędzy poszczególnymi czynnikami a całkowitym czasem przeżycia. Wyniki: Do badania zakwalifikowano 107 pacjentek, które podzielono na 3 grupy: 1) pacjentki z cukrzycą typu 2 stosujące metforminę (n=30), 2) pacjentki z cukrzycą typu 2 nieleczone metforminą (n=38), 3) pacjentki niechorujące na cukrzycę typu 2. Nie zaobserwowano istotnej statystycznie różnicy w czasie całkowitego przeżycia pomiędzy pacjentkami leczonymi a nieleczonymi metforminą (p=0,86). Podobnie stosowanie metforminy, współistnienie cukrzycy typu 2, poziom glukozy we krwi i indeks masy ciała (BMI) nie miały wpływu na przeżycie chorych. Zawężając analizowaną grupę do raka endometrium typu I lub do histologicznego typu endometrioidalnego uzyskano takie same wyniki. Wnioski: Zażywanie metforminy nie ma wpływu na czas całkowitego przeżycia pacjentek chorych na raka endometrium. Współistnienie cukrzycy również pozostaje bez wpływu na przeżycie w tej grupie pacjentek

Carcinoma of the uterine cervix during pregnancy

Pregnancy offers a unique opportunity for the early diagnosis of cervical caner, due to the fact that pregnant patients have many possibilities of gynecological and cytological examinations. There is much evidence that pregnant women have two to three-fold higher chance of having preneoplastic lesions and early, operable stages of disease diagnosed. The preneoplastic lesions do not require any intervention during pregnancy. However, precise, serial colposcopic examinations, completed by biopsy if necessary, must be seriously considered in order to exclude invasive cancer. The only indication for conization during pregnancy is to rule out or confirm microinvasive or invasive cancer, provided such diagnose can change the time and the way of delivery. Invasive cervical cancer diagnose is frequently associated with difficult medical and ethical decisions. The most proper approach should be considered, taking into account the benefit of the mother and the child. The decision is easier in the early stage of cancer, because it has been proven that six- to twelve- week delay of the beginning of the therapy does not deteriorate the cancer outcome but it enables the fetus to acquire sufficient lung maturity. Advanced carcinoma of the cervix forces us to take prompt therapeutic decisions. Both, the continuation of the pregnancy and the administration of neoadjuvant chemotherapy are still possible

Ovarian cancer – modern approach to its origin and histogenesis

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 III 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

Porównanie efektywności cytodiagnostyki, molekularnej identyfikacji DNA i mRNA HPV HR oraz testu CINtecPLUSTM w wykrywaniu zmian LG SIL i HG SIL

Aim of the paper: 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. Material: 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. Method: 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 – CINtecPLUSTM. Results: 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%. CINTecPLUSTM test achieved 100% sensitivity and 67% specificity in the diagnosis of CIN 2 +. Conclusions: 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 actualprecancerous stages - CIN 2 +.Cel pracy: Porównanie konwencjonalnej cytodiagnostyki z identyfikacją molekularną DNA HPV HR i mRNA HPV HR oraz immunocytochemicznym testem na wykrywanie białek supresorowych P16 i jądrowego Ki67 pod kątem wykrywania patologii szyjki macicy w skriningu z podziałem na rozpoznania histopatologiczne LG SIL i HG SIL. Materiał: Analizie poddano 630 wymazów cytologicznych pobranych od kobiet z podejrzeniem patologii szyjki macicy, 558 wymazów na obecność DNA HPV HR, 421 wymazow na obecność mRNA HPV HR, 86 wymazów na obecność białek supresorowych P16 i jądrowego Ki67. U wszystkich badanych kobiet wykonano standardowe badanie kolposkopowe z pobraniem wycinków i abrazję kanału szyjki macicy. Metoda: W badaniach wykorzystano klasyczny wymaz cytologiczny pobierany na szkiełko podstawowe oceniany wg klasyfikacji TBS, kolposkopię realizowaną zgodnie z wytycznymi Międzynarodowej Federacji Patologii Szyjki Macicy i Kolposkopii z roku 2003, diagnostykę molekularną opartą o testy identyfikujące DNA i mRNA HPV HR oraz diagnostykę immunocytochemiczną, czyli test CINTecPLUSTM. Wyniki: Czułość badania cytologicznego identyfikującego zmiany CIN 2+ wyniosła 85%, a specyficzność 23%. Wskaźniki PPV i NPV wyniosły odpowiednio 39% i 72%. Dokładność cytologii osiągnęła poziom 46%. Test DNA HPV HR uzyskał 91% czułość i 33% specyficzność w diagnostyce zmian CIN 2+. Jego dokładność wyniosła 54%. Wartość PPV i NPV dla diagnostyki molekularnej wyniosła odpowiednio 43% i 87%. Dla mRNA HPV czułość metody wyniosła 79%, specyficzność 67%. Test CINTecPLUSTM osiągnął 100% czułość i 67% swoistość w rozpoznawaniu CIN 2+. Wnioski: 1. Cytodiagnostyka konwencjonalna ustępuje pod względem czułości i swoistości zarówno testom molekularnym DNA HPV jak i technice immunocytochemicznej w procesie wykrywania LG SIL i HG SIL. 2. Maksymalną czułość i wysoką swoistość wykrywania rzeczywistych stanów przedrakowych czyli zmian CIN 2+ wykazuje technika immunocytochemiczna