Pegylated liposomal doxorubicin in ovarian cancer treatment

Summary Ovarian cancer treatment after cytoreductive surgery is based solely on chemotherapy. Pegylated liposomal doxorubicin (PLD) is a cytotoxic agent of verified efficacy in the treatment of ovarian cancer and is may be used in the first and the following lines of chemotherapy. In the first-line ovarian cancer treatment the combination of PLD with carboplatin assures a prolonged interval to progression and produces less toxicity when compared to carboplatin with paclitaxel schedule. Calypso trial has also revealed that in platinum-sensitive recurrent ovarian cancer PLD with carboplatin shows better anticancer efficiency in comparison to combination carboplatin with paclitaxel and its toxicity profile is quite unique. Namely, PLD does not cause hematological complications, neuropathy, balding and hair loss that are characteristic of other chemotherapeutics applied in ovarian cancer treatment. Palmar-plantar erythrodysesthesia, a typical and commonly noted adverse event, rarely occurs when the dosage is 40mg/m2 iv. Thus, PLD ought to be the drug of choice in recurrent ovarian cancer treatment, both platinum-sensitive and platinum-insensitive one. In case of partially platinum-sensitive ovarian cancer PLD allows for a longer withoutplatinum period what in turn allows for yet another treatment with platinum, and helps achieve a prolonged interval to progression and progression-free survival time

Wartość diagnostyczna CA125, HE4, ROMA oraz modelu regresji logistycznej w diagnistyce guzów miednicy mniejszej – doświadczenia własne

Objectives: The aim of this study was to compare and evaluate the quality of CA125, HE4, logistic regression model based on CA125 and HE4, and ROMA algorithm in preoperational differential diagnostics of the ovarian tumors. Material and methods: To the study 110 patients enrolled. Based on histopatological examination of removed tumors, they were divided into study group (56 cancer patients) and control one (nonmalignant 54 patients). Serum CA125 and HE4 concentrations were measured following a standard procedure. Results: A commonly accepted referential value for CA125 is 35 IU/ml. In our study, this cut-off value yielded very low sensitivity and specificity results (85.2% and 63.6%, respectively). When we adopted HE4 normal value to be 140 pM,the sensitivity and specificity obtained in the investigated population was 68.5% and 94.6%, respectively. When the cut-off value for HE4 was adopted as 74 pM, the sensitivity improved considerably (88.9%), but specificity decreased to 85.7%. In case of CA125 when we adopted Ca125 normal value to be 77 IU/ml, the sensitivity and specificity obtained in the investigated population was 81.5% and 83.6%, respectively. In analysis based on combination of biomarkers, the highest sensitivity was obtained for the logistic regression model based on CA125 and HE4 (89.5%). A little bit lower sensitivity was achieved for HE4 used as a single diagnostic test (88.9%). The highest specificity was observed for ROMA algorithm (94.5%). This means that ROMA algorithm is the best diagnostic tool to differentiate between the malignant and non-malignant ovarian tumors. Conclusions: 1. ROMA algorithm yielded the highest specificity and slightly lower sensitivity in the case of differential diagnosis between malignant and non-malignant ovarian tumors. Therefore, it should become a basic tool in the ovarian tumors diagnosis prior to a surgery. 2. HE4 as a single diagnostic test (based on one marker) was found to be better suited to the ovarian tumor differential diagnosis than CA125 test. 3. Combined test, based on double marker analysis, should be applied and then the risk of the ovarian cancer should be calculated. This approach is more effective than single marker analysis.Cel pracy: Celem niniejszego badania było porównanie i ocena wartości CA125, HE4, modelu regresji logistycznej oraz algorytmu ROMA w przedoperacyjnej diagnostyce różnicowej guzów przydatków. Materiał i metody: Do badania włączono 110 pacjentki, które na podstawie wyniku badania histopatologicznego usuniętych guzów podzielono na grupę badaną (56 pacjentek z nowotworami złośliwymi) i grupę kontrolną (54 pacjentek ze zmianami niezłośliwymi). Oznaczenie osoczowych stężeń CA125 oraz HE4 wykonano zgodnie z standardową procedurą. Wyniki: Powszechnie uznaną wartością graniczną dla CA125 jest 35 IU/ml. W naszym badaniu, przyjęcie tej wartości punktu odcięcia zaowocowało niskimi wartościami czułości i swoistości – odpowiednio 85,2% oraz 63,6%. Wyjściowo uznaliśmy wartość 140 pM jako punkt odcięcia (wartość sugerowana przez producenta). Dla takiego punktu odcięcia, czułość i swoistość osiągnęły odpowiednio wartość 68,5% i 94,6%. Gdy wartość punktu odcięcia dla HE4 została zmieniona na 74 pM, czułość testu wzrosła do 88,9% a swoistość zmniejszyła się do 85.7%. W przypadku CA125 zmiana wartości punktu odcięcia na 77 IU/ml spowodowała spadek czułości do 81,5% przy jednoczesnym wzroście swoistości do 83,6%. W analizach obejmujących jednocześnie obydwa markery (CA 125 i HE4), model oparty na regresji logistycznej osiągnął najwyższą czułość (89,5%). Niewiele mniejszą wartość czułości osiągnął test oparty na oznaczeniu HE4 (88,9%). Natomiast najwyższą wartość swoistości osiągnął algorytm ROMA (94,5%). Oznacza to że algorytm ROMA jest najlepszym narzędziem diagnostycznym w różnicowaniu złośliwych i niezłośliwych guzów jajnika. Wnioski: 1. Algorytm ROMA osiągnął najwyższą wartość swoistości i niewiele niższą wartość czułości jako narzędzie diagnostyczne w różnicowaniu złośliwych od niezłośliwych guzów jajnika. Dlatego powinien zostać podstawowym narzędziem diagnostycznym przed planowanym leczeniem chirurgicznym. 2. HE4 jako pojedynczy test diagnostyczny osiągnął wyższe wartości czułości i swoistości w porównaniu z CA 125. 3. Jednoczesne oznaczanie dwóch markerów (CA 125 i HE4) oraz obliczanie ryzyka wystąpienia nowotworu złośliwego jest zalecanym postępowaniem u pacjentek z guzami przydatków. Analizy oparte na dwóch markerach są bardziej efektywne niż analizy oparte na pojedynczych markerach

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

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

Semaphorin 3A (SEMA3A), protocadherin 9 (PCdh9), and S100 calcium binding protein A3 (S100A3) as potential biomarkers of carcinogenesis and chemoresistance of different neoplasms, including ovarian cancer — review of literature

Ovarian cancer is the fifth leading cause of cancer-related deaths in women. Its high mortality rate results from lack of adequate and sensitive methods allowing for the detection of the early stages of the disease, as well as low efficiency of the treatment, caused by the cytotoxic drug resistance of cancer cells. Unfortunately, tumours are able to develop new pathways and protective mechanisms that allow them to survive toxic conditions of chemotherapy. Therefore, intensive search for new genes and proteins involved in resistance to cytotoxic drugs is still needed, especially from a clinical point of view. The article presents an overview of the available literature on the role of semaphorin 3A (SEMA3A), protocadherin 9 (PCDH9), and S100 calcium binding protein A3 (S100A3) in carcinogenesis and chemoresistance of various tumors including ovarian cancer. As it turns out, the role of described genes/proteins is not limited only to their native biological activity but they function also as an oncogenic or suppressor factors in the tumor development. Moreover, they can also play an important role in development of drug resistance, as it was shown in ovarian cancer cell lines

Obwodowa neuropatia indukowana chemioterapią — epidemiologia i patogeneza

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most important neurologic complications experienced by patients receiving chemotherapy. The neuropathy often interferes with daily activities and exercise leading to severe impairment of the patient’s quality of life (QoL). The evolution of most CIPNs is characterized by a gradual onset of signs/symptoms, beginning in the lower limbs and advancing proximally into a bilateral stocking and glove distribution. Patients often complain of numbness, tingling and pain in the affected areas. The symptoms become aggravated with repeated cycles of chemotherapy. When the offending agent is withheld, the symptoms generally abate, but relief is not guaranteed. The consequences of delay or discontinuation of treatment may affect overall patient survival.Obwodowa neuropatia indukowana chemioterapią jest jednym z najważniejszych powikłań neurologicznych u pacjentek jej podanych, często zakłócając codzienne aktywności i upośledzając jakość życia a jej objawy pogarszają się przy powtarzanych cyklach chemioterapii. Omówiono stopnie nasilenia neuropatii (Tabela I), jej epidemiologię (szacuje się że doświadcza jej 30% do 55% pacjentów otrzymujących chemioterapię). Jej nasilenie i jakość zależy od czynników osobistego ryzyka (wcześniej istniejące neuropatie, choroby towarzyszące i operacje) i od stosowanego leku (jego typu, sposobu podawania, dawki itp). Omówiono efekty podawania rożnych czynnikowa chemioterapii (docetakselu, winkrystyny, iksabepilonu, oksaliplatyny, cisplatyny, talodomidu, lenalidomidu, bortezomibu), różnice wrażliwości na neuropatię wynikające z polimorfizmu genowego, wieku pacjenta

The role of artificial nutrition in gynecological cancer therapy

Cancer patients are at risk of developing malnutrition from underlying disease as well as from cancer treatment. Moreover, weight loss is considered as a predictive factor for disease progression and shorter survival time. As many as 10–20% of patients with cancer die from the results of malnutrition, instead of from the cancer itself. In the case of cancer-related malnutrition, it is necessary to quickly implement individualized nutritional support depending on the type and stage of the disease, metabolic changes, the patient’s condition, expected survival and the function of the gastrointestinal tract. Artificial nutrition reduces the side effects of chemotherapy and improves immunity. Perioperatively it reduces the risk of infection, facilitates wound healing and shortens the length of hospitalization, thereby reducing the costs of the treat- ment. Initially, a malnourished patient, without gastrointestinal dysfunction, qualifies for nutritional counseling. When the energy needs cannot be met by normal feeding, nutritional supplements, taken orally, are recommended. The next step is to feed the patient by nasogastric tube or percutaneous endoscopic gastrostomy. Parenteral nutrition, which results in more side effects, is only started when enteral nutrition is insufficient to ensure adequate nutritional status or in cases of gastrointestinal tract obstruction. The benefit of parenteral nutrition is that it especially provides for those patients with gynaecological cancer who have radiation-induced intestinal damage and post-surgical complications such as short bowel syndrome. Palliative nutrition must to relieve hunger and thirst. Nutritional interventions should be individualized and focused on the changing nutrient needs of the patient and should be supported by physical activity. Regular assessment of the nutritional status of the patient should be an inherent element of the oncological treatment.

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

Paraneoplastic neurological syndromes associated with ovarian tumors

Introduction: Paraneoplastic neurological syndromes (PNS) are neurologic deficits triggered by an underlying remote tumor. PNS can antedate clinical manifestation of ovarian malignancy and enable its diagnosis at an early stage. Interestingly, neoplasms associated with PNS are less advanced and metastasize less commonly than those without PNS. This suggests that PNS may be associated with a naturally occurring antitumor response. Methods: We review the literature on the diagnosis, pathogenesis and management of PNS associated with ovarian tumors: paraneoplastic cerebellar degeneration (PCD) and anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. An approach to the diagnostic workup of underlying tumors is discussed. Results: PCD can precede the manifestation of ovarian carcinoma. Anti-NMDAR encephalitis in young women appears often as a result of ovarian teratoma. Since ovarian tumors and nervous tissue share common antigens (e.g., cdr2, NMDAR), autoimmune etiology is a probable mechanism of these neurologic disorders. The concept of cross-presentation, however, seems insufficient to explain entirely the emergence of PNS. Early resection of ovarian tumors is a significant part of PNS management and improves the outcome. Conclusions: The diagnosis of PNS potentially associated with ovarian tumor indicates a need for a thorough diagnostic procedure in search of the neoplasm. In some patients, explorative laparoscopy/laparotomy can be considered