Dimitris Tsolakidis

Laparoscopic Management of the Adnexal Mass

Abstract:  In the past few years the contribution of operative laparoscopy in all fields of gynecological surgery has been revolutionary. Nowadays laparoscopic management of adnexal masses is the most frequently performed laparoscopic intervention. Laparoscopy in comparison to laparotomy has the advantages of lower morbidity, shorter length of hospital stay, decreased postoperative pain, lesser de novo adhesion formation, better cosmetic results, faster recovery, and reduced overall cost of care. However, careful preoperative evaluation is important for the appropriate and successful use of laparoscopy for removal of adnexal masses and the advantages of the laparoscopic approach should, in no way, compromise the clinical outcome in women with malignancy. Patients age, history, findings of physical examination, and the results of serum markers in combination with the imaging assessment, such as Doppler sonograpy, CT, or MRI, should be considered to reach the diagnosis preoperatively. However, only pathology of the adnexal mass can provide the definitive diagnosis. The specific characteristics of the adnexal masses in childhood, adolescent, reproductive, and postmenopausal age represent the essential parameters that will determine the therapeutic strategy to be followed. Furthermore, the clinician has to determine whether an adnexal mass requires surgery or expectant management as well as to estimate the possibility of malignancy.

The pro-social neurohormone oxytocin reverses the actions of the stress hormone cortisol in human ovarian carcinoma cells in vitro

The journey patients with ovarian cancer travel from non-specific symptoms causing delayed diagnosis through surgery and chemotherapy, culminating in a 5-year survival rate of 43%, must have a profound and detrimental psychological impact on patients. Emerging studies link higher levels of oxytocin (OT) and increased social support, an independent prognostic factor in cancer, with a moderating effect on stress. In contrast, there is a known association of tumour cell proliferation with elevated cortisol (stress hormone) levels. We hypothesise therefore that there is cross-talk between cortisol and oxytocin at a molecular level. Three ovarian cancer cell lines, used as in vitro models, were treated with cortisol at concentrations mimicking physiological stress in vivo in the presence or absence of OT. OT reduced cell proliferation and migration, induced apoptosis and autophagy for all three cell lines, partially reversing the effects of cortisol. Quantitative RT-PCR of tissue taken from ovarian cancer patients revealed that the glucocorticoid receptor (splice variant GR-P) and OT receptor (OTR) were significantly upregulated compared to controls. Tissue microarray revealed that the expression of GRα was lower in the ovarian cancer samples compared to normal tissue. OT is also shown to drive alternative splicing of the GR gene and cortisol-induced OTR expression. OT was able to transactivate GR in the presence of cortisol, thus providing further evidence of cross-talk in vitro. These data provide explanations for why social support might help distressed ovarian cancer patients and help define novel hypotheses regarding potential therapeutic interventions in socially isolated patients.

Prevalence of occult leiomyosarcomas and atypical leiomyomas after laparoscopic morcellation of leiomyomas in reproductive-age women

STUDY QUESTION What is the prevalence of leiomyosarcomas and atypical leiomyomas after laparoscopic morcellation of fibroids in reproductive age women? SUMMARY ANSWER No case of leiomyosarcomas but seven atypical leiomyomas were found in 1216 subjects. WHAT IS KNOWN ALREADY Although uterine sarcoma is a rare entity affecting usually older peri- or post-menopausal women, the Food and Drug Administration discourages use of laparoscopic power morcellation of uterine fibroids. STUDY DESIGN, SIZE, DURATION Retrospective review of data extracted from a single center database of 1216 consecutive women who underwent laparoscopic morcellation of 2582 unsuspicious leiomyomas between June 2003 and December 2015 and were followed-up until December 2016. PARTICIPANTS/MATERIALS, SETTINGS, METHODS A total of 1216 women, aged 18-45 years, underwent laparoscopic morcellation of 2582 apparently benign leiomyomas by the same surgeon and all specimen slides were examined by the same experienced pathologist. MAIN RESULTS AND THE ROLE OF CHANCE The prevalence of leiomyosarcomas and atypical leiomyomas was 0% (95% CI: 0-0.3%) and 0.6% (95% CI: 0.23-1.18%) (six atypical-bizarre and one mitotically active leiomyoma) respectively. In addition, there were identified 34 cases of adenomyomas, 45 leiomyomas with infarcts, 81 cellular leiomyomas and 133 degenerated leiomyomas. No morcellator-associated complication was recorded and none of the patients included in this study required conversion to laparotomy. LIMITATIONS, REASONS FOR CAUTION Retrospective and single referral center study design. WIDER IMPLICATIONS OF THE FINDINGS Laparoscopic morcellation of unsuspicious leiomyomas after careful preoperative work up seems to be safe in women of reproductive age. STUDY FUNDING/COMPETING INTEREST(S) None.

Differential effects of rapalogues, dual kinase inhibitors on human ovarian carcinoma cells in vitro

Ovarian cancer is the second most common gynaecological malignancy and was diagnosed in over 7,000 women in 2011 in the UK. There are currently no reliable biomarkers available for use in a regular screening assay for ovarian cancer and due to characteristic late presentation (78% in stages III and IV) ovarian cancer has a low survival rate (35% after 10 years). The mTOR pathway is a central regulator of growth, proliferation, apoptosis and angiogenesis; providing balance between available resources such as amino acids and growth factors, and stresses such as hypoxia, to control cellular behaviour accordingly. Emerging data links mTOR with the aetiopathogenesis of ovarian cancer. We hypothesised that mTOR inhibitors could play a therapeutic role in ovarian cancer treatment. In this study we began by validating the expression of four main mTOR pathway components, mTOR, DEPTOR, rictor and raptor, at gene and protein level in in vitro models of endometrioid (MDAH-2774) and clear cell (SKOV3) ovarian cancer using qPCR and ImageStream technology. Using a wound healing assay we show that inhibition of the mTOR pathway using rapamycin, rapalogues, resveratrol and NVP BEZ-235 induces a cytostatic and not cytotoxic response up to 18 h in these cell lines. We extended these findings up to 72 h with a proliferation assay and show that the effects of inhibition of the mTOR pathway are primarily mediated by the dephosphorylation of p70S6 kinase. We show that mTOR inhibition does not involve alteration of mTOR pathway components or induce caspase 9 cleavage. Preclinical studies including ovarian tissue of ovarian cancer patients, unaffected controls and patients with unrelated gynaecological conditions show that DEPTOR is reliably upregulated in ovarian cancer.

New insights of osmoregulatory system changes in ovarian hyperstimulation syndrome

This study evaluated the osmoregulatory system changes in 39 patients with severe ovarian hyperstimulation syndrome. Plasma osmolality (Posm) less or more than 280 mOsm/kg body weight were associated with inappropriate antidiuretic hormone secretion syndrome and hypovolemia, respectively.