2010, Vol 8, no 2
Prevention of HPV-related diseases – clinical and economic aspects of prophylactic vaccination
CURR. GYNECOL. ONCOL. 2010, 8 (2), p. 69-81
ABSTRACT

Cervical cancer is among the most prevalent malignancies in women. Polish National Cancer Registry indicates that in 2007 there were over 3400 new cervical cancer cases and over 1900 women died of this malignancy. The cervical cancer frequently affects women remained productive, hence posses a significant health, social and economic burden. Oncogenic types of human papillomavirus (HPV) 16, 18 present a major causal factor responsible for the development of cervical cancer. Low-oncogenic HPV types 6, 11 are responsible for the development of anogenital warts, non-cancerous tissue growths which are a disturbing condition, considerably diminishing patients’ quality of life and constitute significant financial burden for healthcare system. The standard method of secondary prevention of the HPV-related diseases is cytological screening. Systematic screening is essential nonetheless the test is not specific for HPV. Vaccinations against HPV infection are the only effective method of primary prophylaxis of HPV-related diseases. Currently, there are two registered vaccines: quadrivalent Silgard® vaccine against HPV 6, 11, 16, 18 and bivalent Cervarix® vaccine against HPV 16, 18. The most health and social benefits bring both primary and secondary prevention based on common vaccination against HPV followed by regular cytological screening. Economic analyses indicate that vaccination of 12 years old girls is more cost-effective than the strategy limited to cytological screening only. Polish adaptation of the economic model for routine vaccination program against HPV 6, 11, 16, 18 with quadrivalent Silgard® vaccine reveal cost per QALY (quality adjusted life year) of 17 987 PLN which prove high cost-effectiveness of vaccination against HPV in Poland.

Keywords: infections, HPV, vaccines, cost-effectiveness, cervical cancer
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Application of magnetic nanoparticles in thermotherapy. A review
CURR. GYNECOL. ONCOL. 2010, 8 (2), p. 82-89
ABSTRACT

Nanoscale magnetic materials may have several potential applications in the biomedical area. An example thereof are superparamagnetic iron oxide nanoparticles, which, due to large own surface and ability to interact with various tissues, are used to detect and analyze biological molecules, in targeted drug delivery, for contrast enhancement in magnetic resonance imaging studies and, last but not least, in therapeutic hyperthermia. When used for medical purposes, magnetic nanoparticles often require coating with a biocompatible polymer, preventing its detection by the immune system, encapsulation by plasma proteins and excretion, while at the same time facilitating binding with organic complexes, which subsequently may accumulate in definite pathological foci. Widespread use of magnetic nanoparticles is associated with heat generation. When placed within neoplastic tissue and exposed to alternating external magnetic field, magnetic nanoparticles generate a local heating effect. Local elevation of tissue temperature has a potent cytostatic effect mediated by denaturation of proteins and destruction of intracellular structures, leading to reduction of tumor mass. Temperature obtained within the tumor depends on properties of magnetic nanoparticles used and parameters of external magnetic field applied, i.e. amplitude and frequency of field oscillations. This physical phenomenon results in direct destruction of tumor cells. Furthermore, local elevation of body temperature contributes to enhanced effectiveness of chemo- and radiotherapy. The paper is a review of current applications of superparamagnetic metal nanoparticles in oncology.

Keywords: nanotechnology, oncologic therapy, nanoparticles, hyperthermia, drugs
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Intraperitoneal chemotherapy as first-line treatment of ovarian cancer
CURR. GYNECOL. ONCOL. 2010, 8 (2), p. 90-103
ABSTRACT

Intraperitoneal chemotherapy (IP) in the treatment of ovarian cancer became lately an attractive alternative to standard intravenous chemotherapy. This was a consequence of publication in 2006 of phase III trials indicating that this approach provided clinical benefit as compared with traditional approach in terms of progression-free survival (24 vs. 18 months) and overall survival (66 vs. 50 months, respectively). The present paper reviews theoretical basis of IP, recapitulates milestones of research leading to introduction of IP as first-line therapeutic option and discusses IP-associated adverse effects. Discussion includes impact of IP on patients’ quality of life and effectiveness of other protocols, e.g. those replacing cisplatin by carboplatin. The authors highlight several problems associated with a more widespread use of IP in the treatment of ovarian cancer and indicate novel trends in research, heralded by publications concerning once-weekly administration of paclitaxel. At present, IP as first-line therapy is indicated in FIGO stages II-IV, with residual disease of less than 1 cm after primary cytoreduction. Side effects associated with this therapeutic modality may be classified as drug-dependent and catheter-dependent. The may be minimized by proper selection of patients and port-care. At present, several clinical trials are underway, testing other dosage regimens and chemotherapy protocols. Concomitantly, clinical trials being performed, enable inclusion of patients after IP chemotherapy.

Keywords: ovarian cancer, first-line therapy, intraperitoneal chemotherapy, IP-associated adverse effects, cisplatins
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Analysis of topotecan-associated adverse effects in patients with ovarian cancer
CURR. GYNECOL. ONCOL. 2010, 8 (2), p. 104-111
ABSTRACT

Aim of paper: To assess the incidence of adverse effects occurring in patients receiving intravenous and oral topotecan for ovarian cancer. Material and method: Clinical data on 21 patients treated for ovarian cancer at the Department of Surgical Gynecology of the K. Marcinkowski Medical University in Poznań, Poland, since 2007 thru 2009. Topotecan was administered intravenously at a dose of 1.5 mg/m2/d for 5 days, or orally at a dose of 2.3 mg/m2/d for 5 days. Analysis encompassed clinical and laboratory data related to 92 chemotherapy courses (39 intravenous and 53 oral). Results: In the intravenous group, grade 1 leucopenia was seen in 2 cases out of 39 courses (5.1%). In the oral group, there was 1 case of grade 1 leucopenia (1.9%) and 2 cases of grade 2 leucopenia out of 53 courses (3.8%). In the intravenous group, grade 1 anemia was noticed in 12 out of 39 courses (30.8%), grade 2 anemia – in 14 out of 39 courses (35.9%) and 1 case of grade 3 anemia (2.6%). In the oral group, grade 1 anemia occurred in 14 out of 53 courses (26.4%), grade 2 anemia – in 11 cases (20.8%) and grade 3 anemia – in 1 case (1.9%). No cases of grade 4 anemia or thrombocytopenia were recorded. Conclusions: In our population of patients treated for malignant tumors of the ovary, a similar rate of topotecan-associated hematologic complications was noticed after intravenous and oral administration of the drug.

Keywords: malignant tumor of ovary, ovarian cancer, chemotherapy, topotecan, adverse effects
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Cervical cancer during pregnancy. Diagnostic problems and potential complications
CURR. GYNECOL. ONCOL. 2010, 8 (2), p. 112-122
ABSTRACT

Invasive cervical cancer is the type of malignancy occurring most often during pregnancy and the incidence thereof is estimated at 1:1200 to 1:2200 cases. In the course of pregnancy, early stages of this tumor are usually detected. Typical symptoms of cervical cancer, i.e. vaginal bleeding, fluor and pain are highly non-specific and may be misdiagnosed as pregnancy-related phenomena. Oncologic and cytological diagnosis are an important component of prenatal care. When cytological study in a pregnant woman proves suspicious, the recommended modality for further diagnostic work-up is colposcopy. The main duty of a healthcare professional faced with a pregnant woman with pathological cytological findings is to exclude (or confirm) stromal invasion. Usually, close colposcopic-cytological supervision is recommended, and in the case of suspected stromal invasion – cone biopsy of the cervix. During pregnancy, cervical biopsy and conization of cervix are reserved for cases where invasive disease can not be ruled out by any other method, e.g. cytology, colposcopy or imaging studies. Imaging diagnosis should be implemented for the sake of clinical staging only and be limited to modalities associated with the lowest possible dose of ionizing radiation. Methods of choice include magnetic resonance imaging and ultrasonography. Curettage of cervical canal is not recommended. Diagnostic work-up requires vast experience and sound clinical judgment on the part of the examiner, enabling differentiation of pathological lesions from pregnancy-related physiological conditions. Progression of preinvasive disease to invasive stage during pregnancy is extremely rare. Studies confirmed possible regression of CIN lesions after termination of pregnancy. Chances for regression correlate with type of delivery, increasing after vaginal delivery. Pregnancy does not influence the course of disease at invasive stage, does not alter its prognosis or clinical characteristics. Caesarean section is recommended only in the case of suspected invasive cancer. There are few studies dealing with fetal complications associated, precluding any general conclusions. However, studies revealed an elevated proportion of newborns with low birth weight born by mothers at an invasive stage.

Keywords: cervical cancer, pregnancy, diagnosis, treatment, complications
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Chemotherapy during pregnancy
CURR. GYNECOL. ONCOL. 2010, 8 (2), p. 123-131
ABSTRACT

Chemotherapy in the treatment of malignant tumors in pregnant women potentially threatens life and development of the fetus. Aim of paper: The purpose of this paper was to update current knowledge concerning the role of chemotherapy in combination therapy of gynecologic malignancies complicating pregnancy and to review available literature focusing on potential sequels of administration of chemotherapeutics at different time-points in pregnancy, with particular emphasis on fetal development, course of pregnancy and future lot of the child. Method: The PubMed database was searched using the following key words: methotrexate; 5-fluorouracil; aminopterin; thioguanine; mercaptopurine; cyclophosphamide; busulfan; ifosfamide; chlorambucil; dacarbazine; doxorubicin; daunorubicin; adriamycin; idarubicin; epirubicin; dactinomycin; bleomycin; mitoxantrone; vincristine; vinblastine; vinorelbine; paclitaxel; docetaxel; cisplatin; carboplatin; prednisone; tamoxifen; etoposide; teniposide; allopurinol; malformation; IUGR; chemotherapy; pregnancy. Search criteria were fulfilled by 33 papers (selected chemotherapeutic agent/pregnancy/malformation), which subsequently underwent content-related analysis. Conclusions: A decision on the use of chemotherapy during pregnancy should be made depending on type and stage of malignancy. It at all possible, administration of cytostatics should be delayed until the end of first trimester. If the patient requires multidrug therapy in the first trimester, she should receive anthracycline-derived antibiotics combined with Vinca alkaloids or should be placed on monotherapy and after 12 weeks shift to a multidrug regimen. Delivery should be planned for the 35th gestational week and 2-3 weeks after termination of chemotherapy in order to allow recovery of bone-marrow function.

Keywords: chemotherapy, pregnancy breast cancer, leukemia, cervical cancer
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Role of ghrelin and obestatin in metabolic processes and in neoplastic conditions in humans
CURR. GYNECOL. ONCOL. 2010, 8 (2), p. 131-138
ABSTRACT

Both ghrelin and obestatin are peptides derived from the same precursor – preprohormone – encoded on the 3rd chromosome (3p25-26). Both hormones are secreted to the bloodstream. Ghrelin has 28-amino acids with serine at position 3. It is an endogenous ligand of growth hormone receptor (GHS), which has been discovered in hypophysis and hypothalamus. Ghrelin may occur in active and inactive forms. In order to achieve biological activity, ghrelin must contain a N-octa-acetyl group of serine. Total ghrelin is a sum of active and inactive forms. Ghrelin and its receptors GHS-R1a and 1b (growth hormone secretagogue) are widespread in the body, being present mainly in the gastrointestinal tract, central nervous system, reproductive system, heart and kidneys. Obestatin is a recently discovered 23-amino acids long peptide, produced as a result of proteolytic splitting of the preprohormone ghrelin. Systemic distribution of ghrelin is less well known. Both ghrelin and obestatin play a role in energy management (control appetite, body mass, metabolism of fat and glucose, gastrointestinal function), influence cardiovascular, reproductive and immune systems and participate in modulation of central nervous system function. Ghrelin and obestatin regulate processes of cellular proliferation and apoptosis. Variations of ghrelin and obestatin levels, as well as expression of GHS-R in hypophyseal and neuroendocrine tumors, uterine myomas and both benign and malignant ovarian tumors, confirm their role in tumor development and are a promising topic for future studies in oncology.

Keywords: ghrelin, GHS-R, obestatin, metabolism, tumors
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