Nikolaos Thomakos

VEGF directly suppresses activation of T cells from ovarian cancer patients and healthy individuals via VEGF receptor Type 2.

The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis is well characterized; nevertheless, it is also a key element in promoting tumor evasion of the immune system by downregulating dendritic cell maturation and thus T cell activation. We sought to investigate the possible direct effect of VEGF on T cell activation and through which type of VEGF receptor (VEGFR) it exerts this effect. Circulating T cells from healthy donors and ovarian cancer patients were expanded in cultures with anti‐CD3 and IL‐2 with or without VEGF for 14 days, and the number of T cells was assessed. Cultured T cells were also tested for their cytotoxic activity in a standard 4‐hr 51Cr‐release assay, and the expression of VEGFRs 1, 2 and 3 was assayed by flow cytometry, immunocytochemistry and Western blotting. To assess the ability of activated T cells to secrete VEGF, levels in culture supernatants were measured by enzyme linked immunosorbent assay. The addition of VEGF in cultures significantly reduced T cell proliferation in a dose‐dependent manner. Protein expression studies demonstrated that CD3+ T cells express VEGFR‐2 on their surface upon activation. Experiments with anti‐VEGFR‐2 antibodies showed that the direct suppressive effect of VEGF on T cell proliferation is mediated by VEGFR‐2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells and that activated T cells secrete VEGF in the culture environment. Overall, our study shows that T cells secret VEGF and expresses VEGFR‐2 upon activation. VEGF directly suppresses T cell activation via VEGF receptor type 2.

Sonographic Cervical Length Measurement before Labor Induction in Term Nulliparous Women

Objective: The purpose of the study was to determine if transvaginal sonographic measurement of the cervical length is a useful method to predict successful labor induction in nulliparas. Methods: 137 women who were scheduled for medically indicated induction of labor had a transvaginal sonographic measurement of the cervical length before labor induction. Inclusion criteria were: (1) singleton pregnancy; (2) gestational age between 37–42 weeks; (3) live fetus in cephalic presentation; (4) intact membranes; (5) no vaginal bleeding; (6) no previous history of uterine surgery; (7) nulliparous women, and (8) no allergy or asthma in response to prostaglandins. Induction of labor was performed within 6 h of the ultrasonographic examination, by inserting 2 mg of dinoprostone in the posterior vaginal fornix, repeated if needed every 6 h for up to three doses. When the cervix became favorable and no regular contractions were observed, amniotomy and oxytocin augmentation, starting at 1 mIU/min and increasing 1 mIU every 30 min as necessary, was performed. Results: All women were Caucasians and the mean age was 24.3 years (range 19–37 years). The mean cervical length was 28 mm (range 11–39 mm). The Bishop score was ≤5 in 101 women and >5 in the 36 others. Vaginal delivery occurred in 92 women (67.1%), and the vast majority of them (89 women; 96.7%) gave birth within 24 h of induction. Forty-five women (32.8%) had a cesarean section. The Bishop score was not predictive of the mode of delivery. Thirty-six of 101 women (35.6%) with a Bishop score ≤5 delivered by cesarean section, compared to 9 of 36 women with a Bishop score >5 (25%) (p = NS). Women with a cervical length <27 mm were more likely to deliver vaginally. Using this cutoff value the sensitivity of a successful labor induction was 76% and the specificity was 75.5%. Conclusions: Transvaginal sonographic measurement of cervical length is a good predictor of a successful labor induction at term in nulliparas.

Risk factors in women 40 years of age and younger with endometrial carcinoma

Objective. To identify and compare risk factors among endometrial cancer patients ≤40 years of age, postmenopausal women with the same malignancy and women ≤40 years without malignancy. Design. Retrospective case–control study. Setting. Athens University, department of obstetrics and gynecology of a tertiary hospital serving a mainly urban population. Population. Endometrial cancer patients ≤40 years (study group, n = 40), postmenopausal women with the same malignancy (positive controls, n = 40) and women ≤40 (negative controls, n = 40) without endometrial cancer. Methods. Clinical history, treatment and follow‐up of patients were evaluated. Factors studied included age, histology, stage, grade, lymphovascular space involvement, body mass index (BMI), cytology, lymph node status, parity, smoking, family history, hypertension recurrence and survival. Main outcome measures. Differences in risk factors and characteristics. Results. Nulliparity, smoking and hypertension were significantly related with endometrial cancer in the study group compared to positive controls (p = 0.001, p < 0.01 and p < 0.001, respectively). BMI >30 significantly characterized patients in the study group compared to negative controls (p = 0.006). Finally, irregular menstruation and family history of cancer were observed more often in the study group compared to both control groups. Stage, grade, myometrial invasion, lymphovascular space involvement and lymph node status were comparable between the study and positive control groups. Conclusion. Nulliparity, obesity, unstable menstruation, smoking and cancer in the family are strongly correlated with endometrial cancer risk in women ≤40 years.

A rare case of rectovaginal endometriosis with lymph node involvement.

A rare case of rectovaginal endometriosis with lymph node involvement is described in a 44-year-old patient. The presence of endometrial tissue in pelvic lymph nodes is rare and has been confirmed in the literature in subjects who underwent surgery for endometriosis. Involvement of pelvic lymph nodes by endometriosis seems unlikely to arise de novo and probably suggests lymphatic spread of the disease.

Role of chromosome 3q26 gain in predicting progression of cervical dysplasia.

Objective This study aimed to determine whether 3q26 gain can predict which low-grade squamous intraepithelial lesions (LSILs) and atypical squamous cells of undetermined significance (ASCUSs) will progress to higher-grade squamous intraepithelial lesion (HSIL). Methods Liquid cytology specimens of LSIL and ASCUS from 73 women were examined using fluorescent in situ hybridization (FISH) for the detection of 3q26 gain. All women underwent colposcopy and biopsy at the initial visit and 40 of them with histology showing cervical intraepithelial neoplasia 1 (CIN 1) or human papillomavirus infection (koilocytosis) were included in the study. They were reevaluated with liquid cytology, colposcopy, and biopsy after a median follow-up of 17.5 months. Results A total of 40 cases were analyzed (31 LSILs and 9 ASCUSs). Of these cases, 8 (20%; 6 LSILs and 2 ASCUSs) were positive and 32 (80%) were negative for 3q26 gain according to FISH. Three of the 8 positive women (38%) progressed to HSIL/CIN 2 or worse, whereas none of the 32 negative women did so. 3q26 gain could predict progression with a negative predictive value of 100% (95% confidence interval, 89.1%–100%). In addition, women positive for 3q26 gain had a significantly lower regression rate compared with negative women (P = 0.009). Conclusions In this first prospective study, 3q26 gain in LSIL/ASCUS cytology exhibited an impressive negative predictive value for progression to HSIL/CIN 2 or worse. Thus, 3q26 gain may be useful in stratifying patients’ risk for progression and possibly alter management and reduce cost of follow-up.

Cervical assessment in women with threatened preterm labor.

Objective. The aim of the study was to examine the clinical value of cervical assessment by transvaginal ultrasonography in women with symptoms of preterm labor. Methods. We prospectively evaluated 172 women with singleton pregnancies and symptoms of preterm labor. Seventy of them were nulliparas, while 102 were multiparas. Gestational age ranged between 24 and 34 wks. All women underwent cervical assessment with transvaginal ultrasonography and were given intravenous tocolytics. The only parameter evaluated was cervical length. Women with multiple pregnancies, gestational age < 24 wks or > 34 wks, cervical dilatation > 2 cm, placenta praevia, premature rupture of membranes, or cervical cerclage were excluded from the study. The outcome measure was delivery before 34 wks gestation. Results. The preterm delivery rate before 34 wks was 37%. The sensitivity and the specificity of a cervical length of less than 20 mm was 60 and 53.8% and 97.7 and 95.2% for nulliparas and multiparas, respectively. A cervical length < 20 mm was also 93.7% predictive of preterm delivery in nulliparas and 87.5% in multiparas, while the corresponding numbers for its negative predictive value (NPV) were 81.4 and 76.9%, respectively. Conclusions. Cervical assessment in women with symptoms of preterm labor can distinguish those at high risk for preterm delivery. Cervical sonography can be a valuable adjunct to the clinical evaluation of these patients.

Improved Survival Trends in Platinum-Resistant Patients with Advanced Ovarian, Fallopian or Peritoneal Cancer Treated with First-Line Paclitaxel/Platinum Chemotherapy: The Impact of Novel Agents

Objective: The prognosis for patients with platinum-resistant advanced ovarian cancer remains poor. The impact of approved agents on survival has not been clarified during the last decade. We studied survival trends during the last 15 years in platinum-resistant patients treated with cytoreductive surgery followed by paclitaxel/platinum chemotherapy. Methods: Patients with epithelial ovarian, fallopian or peritoneal cancer, stages III/IV and platinum-resistant disease after first-line chemotherapy with paclitaxel/platinum were included. They were grouped according to the period of chemotherapy: group A 31/3/1995–31/12/2001 (n = 56) and Group B 1/1/2002–24/12/2008 (n = 57). In order to compensate for the difference in follow-up between the 2 groups, we performed minimum follow-up (MFU) analyses by considering as cases only women who had an event within 3 years of follow-up. Patients with no events for up to 3 years were censored at that time. Results: MFU analyses showed that median overall survival (OS) was significantly longer in group B: 12.3 vs. 17.5 months (p = 0.012). This was due to a doubling of the median OS after relapse: 5.7 vs. 10.9 months (p = 0.0180). Multivariate Cox regression indicated group and histology as factors statistically significantly associated with OS. Following relapse, patients in group B were predominantly treated with liposomal doxorubicin and gemcitabine, and patients in group A were treated with platinum compounds, docetaxel and oral etoposide (p < 0.001). Conclusions: The introduction of novel agents without cross-resistance to platinum or taxanes has improved the prognosis of platinum-resistant patients.

Cesarean vs. vaginal birth for term breech presentation in 2 different study periods

Objective: To compare outcomes for fetuses at term in breech presentation during 2 periods when different delivery policies were in effect. Methods: Outcomes of the 392 planned vaginal deliveries and 1160 elective cesarean sections (CSs) performed from January 1, 1988, through December 31, 2000, were compared with those of the 24 emergency vaginal deliveries, the 403 planned CSs, and 75 emergency CSs performed from January 1, 2001 through December 31, 2004 at Alexandra Hospital, Athens, Greece. Results: A significant difference was found in rates of low 5‐minute Apgar score, birth trauma, serious neonatal morbidity, and admission to the neonatal intensive care unit (0% vs. 1.02% [P = 0.004], 1.02% vs. 0% [P = 0.004], 3.06% vs. 0.43% [P < 0.001], and 2.8% vs. 0.43% [P < 0.001], respectively) between neonates born by planned vaginal delivery and those born by elective CS during the first period. Only a reduction in rates of admission to the neonatal intermediate care unit was found between the first and second periods. Conclusions: Planned CS was found to be safer than planned vaginal delivery for fetuses at term in breech presentation. However, the study did not demonstrate that the change in policy improved neonatal outcome.

Laparoscopically assisted vaginal radical hysterectomy: systematic review of the literature.

Laparoscopically assisted vaginal radical vaginal hysterectomy (LAVRH), a minimally invasive technique that seems to be an attractive alternative to traditional surgery, remains unexplored in the treatment of cervical cancer. We searched Medline (1966-2013) and Scopus (2004-2013) search engines, as well as reference lists from all included studies. Ten studies were retrieved; including 6 retrospective cohort studies, 2 prospective cohort studies, 1 retrospective randomized trial, and a phase II randomized control trial. LAVRH provided equal recurrence-free rates when performed in patients with tumors not exceeding 2 cm in greatest diameter. Its main advantages seem to be less intraoperative blood loss and more radical pelvic lymphadenectomy. The primary disadvantages of the technique are a higher rate of disease-positive surgical margins, resulting in the need for adjuvant therapy, and the slow learning curve required for a surgeon to gain expertise. With use in minimally invasive surgery of newer techniques such as total laparoscopic radical hysterectomy and robotic-assisted radical hysterectomy, and possible future adoption of more conservative techniques such as cervical conization with pelvic lymphadenectomy, the question remains as to whether LAVRH will be adopted by the surgical community or lost to oblivion.

Less Radical Surgery for Fertility Preservation in Patients with Early-Stage Invasive Cervical Cancer Contemporary Problematics

Cervical cancer, is a middle age women’s disease. Nowadays, because of the postponement of childbearing at older age, women younger than 45 years old who are diagnosed with cervical cancer, have a strong desire for preserving fertility. For this reason, Radical Trachelectomy (Vaginal and Abdominal) is used worldwide. In this article, we review data on procedures for fertility preservation, namely Radical Trachelectomy, less invasive procedures and Neoadjuvant Chemotherapy, based on the literature over the past 12 years. Oncological and Obstetrical outcomes are analyzed. In conclusion, Radical Trachelectomy, is an oncologically safe procedure for women with early invasive cervical cancer. However, a number of considerations regarding the selection criteria, patient’s information and especially the complications and the postoperative quality of life, should be taken into account.