Epithelial Ovarian Cancer

Epidemiology

The ovarian cancer is the third more common malignancy of the female genital system in Europe and USA, after the endometrial and cervical cancer (1.4% is the incidence of the ovarian cancer in the female population). In addition, the epithelial ovarian cancer is the most common histological type of the ovarian malignancy (90%) (Figure 1,2). The 2/3 of the patients with epithelial ovarian carcinoma are diagnosed in advanced stage (ΙΙΙ-ΙV), making the prognosis of such patients worse.

Risk factors

The cumulative number of the ovulation during the life of the women remains the strongest risk factor related to the epithelial ovarian malignancy. Actually, prolonged reproductive lifetime period increase the oncogenic effect of the monthly ovulation in the epithelium of the ovaries. However, meta-analysis concerning the ovulation induction during ARTs (artificial reproductive technologies), did not show significant incidence of ovarian cancer in such women compared to the women of general population.
The hereditary ovarian cancer is rare type of ovarian malignancy (< 10%). The mutation of the oncogenes BRCA1 & BRCA2 is the genetic base of the hereditary breast-ovarian cancer. Women-carriers of both BRCA1 & BRCA2 mutations have a life-threatening rate of ovarian carcinoma almost 40%, while in presence of one mutation the relative rate of ovarian cancer is 10%, respectively. In addition the Hereditary Non-Polypossis Colorectal Cancer (HNPCC) is genetic syndrome related to malignancy with increase risk for intestinal, ovarian, breast and uterine cancer.
Πίνακας 1
Πρώιμη εμμηναρχή
Καθυστερημένη εμμηνόπαυση
Ατοκία
Υπογονιμότητα
Λήψη ψυχοτρόπων φαρμάκων
Χρήση ταλκ (διεγχειρητικά)
Κληρονομικός καρκίνος

Η παραγωγή και η απελευθέρωση στην κυκλοφορία του αίματος μεγάλων ποσοτήτων γοναδοτροφινών, επιδρά στη μεταλλαξιογένεση των επιθηλιακών κυττάρων της ωοθήκης. Παρόλα αυτή η συμβολή της πρόκλησης ωοθυλακιορρηξίας στον επιθηλιακό καρκίνο της ωοθήκης δεν έχει επιβεβαιωθεί. Μετά-αναλύσεις καταδεικνύουν μικρή μόνο αύξηση του κινδύνου εμφάνισης οριακών όγκων ωοθηκών (borderline) σε γυναίκες που έχουν υποβληθεί σε πρόκληση ωοθηλακιορρηξίας με γοναδοτροφίνες.

Ο κληρονομικός καρκίνος της ωοθήκης, πιο σπάνιος (< 10%), οφείλεται σε μεταλλάξεις των ογκοκατασταλτικών γονιδίων BRCA1 και BRCA2 και ανήκει στο πλαίσιο του κληρονομικού καρκίνου μαστού-ωοθηκών. Μεταλλάξεις και των δύο ανωτέρω γονιδίων, συμβάλουν στην εμφάνιση καρκίνου της ωοθήκης σε ποσοστό περίπου 40%, ενώ το αντίστοιχο ποσοστό για τις περιπτώσεις ανεύρεσης ενός εκ των δύο μεταλλάξεων περιορίζεται στο 10%. Ακόμη, το σύνδρομο κληρονομικού μη πολυποδιακού ορθοκολικού καρκίνου (Hereditary Non-Polypossis Colorectal Cancer, HNPCC) αποτελεί επιπλέον παράγοντα κινδύνου ανάπτυξης καρκίνου των ωοθηκών, όπως και καρκίνου παγκρέατος, μαστού και μήτρας.

Αμφοτερόπλευρος επιθηλιακός καρκίνος ωοθηκών
Figure 1. Bilateral epithelial ovarian cancer
Ευμεγέθης επιθηλιακός καρκίνος ωοθήκης (μονόπλευρος)
Figure 2. Controlateral gross epithelial ovarian cancer
Diagnosis Transvaginal (TVUS) and transabdominal (TAUS) ultrasonography is the main tool for the diagnosis of adnexal pathology. Ovarian tumors with solid parts (especially without acoustic shadows), multilocular cystic tumors, ovarian cyst with thick diaphragms or nodular villous (> 7mm), ascites, or peritoneal metastasis are some of the ultrasound characteristics that classified the ovarian or adnexal tumor as suspicious for malignancy. The RMI and the IOTA-ADNEX model are the most popular models, which are used for the precise classification of the different ovarian masses concerning the risk of malignancy.
Furthermore, CA-125, CA19-9, CEA are the most useful biomarkers which are used in the diagnosis of ovarian malignancy especially of epithelial ovarian cancer. However, it is already known that the former markers are elevated as well as in many benign Gynecologic diseases such as endometriosis, gross leiomyomas, pelvis infections etc.
Further imaging with computerized tomography (CT) or magnetic resonance imaging (MRI), may contribute to the investigation of metastasis of the peritoneal or retro-peritoneal space, in case of invasive ovarian carcinoma. In addition MRI could be a useful tool for the differential diagnosis of equivocal ovarian masses according the ultrasound investigation.
Treatment

The surgical staging, after the histological documentation of the ovarian cancer is the oncologic standard of the treatment of the ovarian malignancy. The histological documentation can be done via laparoscopy or laparotomy (cystectomy or adnexectomy), putting the cystic mass in endo-bag in case of laparoscopy to avoid the peritoneal spread of cancer cells. Permanent biopsy or frozen section (during the operation) can offer a definitive diagnosis, for the further approach of the ovarian malignancy.
Surgical staging of the ovarian cancer includes:
  • Peritoneal cytology
  • Total hysterectomy with bilateral salpingo-oophorectomy
  • Omentectomy
  • Pelvic & paraortic lymphadenectomy
  • Biopsies from suspicious peritoneal areas
In case of patients with advanced cancer (stage ΙΙΙ-ΙV), the cyto-reductive surgery is of critical significance. The optimal cyto-reduction with no residual tumor in peritoneal cavity (optimal debulking), is of main significance for the postoperative (adjuvant) chemotherapy and for the future patients prognosis.

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Kalogiannidis doctor

IOANNIS Α. KALOGIANNIDIS MD, PhD

Associate Professor
Obstetrics Gynecology -
Gynecologic Oncology

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