The prognostic role of preoperative serum CA 125 levels in patients with endometrial carcinoma.

PURPOSE: Previous studies have shown that elevated preoperative serum CA 125 levels strongly correlate with various clinical and pathological variables and prognosis of patients with endometrial carcinoma (EC). The aim of the present study was to evaluate the clinical significance of preoperative serum CA 125 levels in patients with EC. METHODS: A retrospective study of all EC patients treated at our institution between 1995 and 2010 with available follow-up was conducted. The preoperative serum level of CA 125 was measured in 99 patients and evaluated in relation to various clinical and pathological variables and outcome. We used the cut-off level of 20 U/ml for CA 125 on chi-square test for categorical variables. Survival analysis was performed with the use of Kaplan Meier method, the log rank test and Cox proportional hazards regression analysis. RESULTS: In the early stages of disease the mean values of CA 125 were 35 U/ml (SD±70) for stages IA-IB and 21 U/ml (SD±29) for stage IC (Mann-Whitney test for continuous variables). In advanced stages of disease (III-IV), the values of preoperative serum CA 125 levels were statistically increased, with mean value 54 U/ml (SD±44), in comparison to stages IA-IB (p=0.02) and IC (p=0.007). According to the multivariate analysis, elevated preoperative serum CA 125 level (p=0.043) and histological tumor type (p=0.004) were independent prognostic factors for disease free survival (DFS) and overall survival (OS) of patients with EC. CONCLUSION: The current study suggests that measurement of preoperative serum CA 125 is a useful clinical tool in the prognosis of patients with EC.

Inheritance and perinatal consequences of inherited thrombophilia in Greece.

OBJECTIVE: To investigate the impact of inherited thrombophilic factors on the gestational outcome of unselected pregnant women. METHOD: A total of 392 women with spontaneous pregnancy were investigated for Factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations. Adverse pregnancy outcomes were recorded. RESULTS: Thrombophilic genotypes were significantly higher in women with placental abruption. Heterozygocity for Factor V Leiden increased the risk for placental abruption 9.1 times. The MTHFR T677T genotype increased the risk for placental abruption 4.8 times despite folate supplements, and normal serum folate and B(12) levels. Women with inherited thrombophilia and previous obstetric complications were at significant risk for complications in a subsequent pregnancy (P<0.05). CONCLUSION: Women with placental abruption should be screened for thrombophilic factors and plasma homocysteine should be measured. Subgroups of women with inherited thrombophilia and obstetric complications might benefit from prophylactic anticoagulation in subsequent pregnancies.

Expression of phosphorylated Akt, mTOR and MAPK in type I endometrial carcinoma: clinical significance.

BACKGROUND/AIM: The Akt/mTOR and MAPK pathways are frequently activated in various tumor types but data on endometrial carcinoma are limited. The aim of the present study was to investigate the clinical significance of the expression of phosphorylated MAPK, Akt and mTOR (p-MAPK, p-Akt, p-mTOR) in type I endometrial carcinoma. MATERIALS AND METHODS: The study comprised of 103 formalin-fixed paraffin-embedded (FFPE) type I endometrial carcino ma cases, retrospectively retrieved and assessed by immuno histochemistry for p-MAPK, p-Akt and p-mTOR expression. The expression of these proteins was also studied in non-neoplastic endometrial tissue adjacent to the tumor. RESULTS: The expression patterns of these molecules differed between malignant and non-tumorous tissue specimens. The immuno reactivity for p-Akt was exclusively detected in the neoplastic tissues. Expression levels of p-MAPK were higher in tumors compared to non-neoplastic endometrium (p<0.001), while p-mTOR was found to be over-expressed in non-neo plastic endometrium compared to carcinomas (p=0.001). Expression of p-Akt was correlated with p-MAPK protein levels (p=0.022, r=0.229). On the other hand, no association was found with clinicopathological parameters and with disease-free (DFS) or overall survival (OS) of the patients. CONCLUSION: Our findings support the de-regulation of the PI3K/Akt/mTOR and MAPK signaling pathways in type I endometrial carcinomas suggesting involvement of these pivotal pathways in endometrial carcinogenesis.

Necrotizing fasciitis complicating pregnancy: a case report and literature review.

Necrotizing fasciitis is a rare, life-threatening surgical infection in pregnancy with high rates of morbidity and mortality. A 15-year-old primigravid woman, at 28 weeks of gestation with no significant previous medical history, was admitted to our hospital complaining of severe left lower extremity pain and high fever the last 72 hours. During clinical examination, she had a swollen, erythematous and tender to palpation inflamed skin over the medial aspect of the upper thigh without any evidence of injury. Incision drainage was performed immediately and she received broad spectrum antibiotics. During initial laboratory examinations, diabetes mellitus was diagnosed. There was no clinical improvement over the following days. Magnetic resonance imaging (MRI) revealed subcutaneous tissue inflammation and edema of infected tissues confirming the disease entity. Multidisciplinary therapy with immediate aggressive surgical debridement of necrotic tissues, multiple antibiotics, and intensive care monitoring was performed successfully. The patient's postoperative course was uncomplicated and skin defect was closed with split thickness skin grafting. Our case emphasized the potential immunosuppressive role of pregnancy state in conjunction with diabetes mellitus in the development of severe necrotizing soft tissue infections.

An immunohistochemical analysis of sex-steroid receptors, tumor suppressor gene p53 and Ki-67 in the normal and neoplastic uterine cervix squamous epithelium.

INTRODUCTION: Malignant transformation of sex-steroid dependent tissues is associated with the loss of expression of sex steroid receptors as well as of the tumor suppression gene p53. The aim of this study is to evaluate the expression of sex-steroid receptors, p53 and Ki-67 in specimens from pre-malignant and malignant cervical epithelial lesions throughout the menstrual cycle. MATERIAL AND METHODS: Immunohistochemical staining was performed on formalin fixed, paraffin embedded tissue sections of normal squamous cervical epithelium, cervical intraepithelial neoplasia and invasive squamous cervical carcinoma, specimens utilizing antibodies against estrogen receptors, progesterone receptors, p53 protein and Ki-67 antigen. RESULTS: In the samples taken from the normal cervical tissue, basal cells were usually estrogen receptor-positive, progesterone receptor-negative, p53-negative and Ki-67-negative throughout the menstrual cycle. In contrast, para-basal cells were estrogen receptor-positive and progesterone receptor-negative in the follicular phase, but estrogen receptor-negative and progesterone receptor-positive and Ki-67 positive in the luteal phase. In cervical precancerous and cancer tissue samples (cervical intraepithelial neoplasia and squamous cervical carcinoma), the expression of estrogen receptors decreased. 31.15% of cervical intraepithelial neoplasia and 11.5% of squamous cervical carcinoma were positive for estrogen receptors. However, the expression of progesterone receptors increased. 29.5% of cervical intraepithelial neoplasia and 49.2% of squamous cervical carcinoma were positive for progesterone receptors. Positive staining for p53 was observed in 15 (24.59%) cases of cervical intraepithelial neoplasia and in 39 (64%) of squamous cervical carcinoma. The expression Ki-67 index in squamous cervical carcinoma cases (47.60%) was significantly higher than of cervical intraepithelial neoplasia cases (30.2%) (p = 0.041). CONCLUSION: The findings of this study suggest that tumor cervical cells evade normal growth control by sex steroid hormones while synchronously abnormal regulatory mechanisms acquire control of the cell cycle.

Mid-trimester maternal serum HCG and alpha fetal protein levels: clinical significance and prediction of adverse pregnancy outcome.

CONTEXT: Maternal serum human Chorionic Gonadotropin (hCG) and Alpha Fetal Protein (AFP) were originally introduced to detect trisomy 21 and neural tube defects. However, in the absence of aneuploidy or neural tube defects, mid-trimester maternal serum hCG and/or maternal serum AFP associated with adverse pregnancy outcomes. Pregnancies with unexplained mid-trimester elevation in maternal serum hCG and/or maternal serum AFP, are at increased risk for pregnancy complications resulting from placental insufficiency. EVIDENCE ACQUISITION: Mid-trimester maternal serum hCG>2.5 MoM associated with an increased risk for pregnancy complications including: late fetal loss, gestational hypertension, preeclampsia, intrauterine growth restriction (IUGR), preterm delivery and intrauterine fetal death(IUFD). Mid-trimester maternal serum AFP levels >2.5 MoM are thought to reflect a defect in placentation and associated with an increased risk for pregnancy complications including: late fetal loss, gestational hypertension, preeclampsia, IUGR, preterm delivery and IUFD. RESULTS: Combined mid-trimester elevation in maternal serum hCG and AFP levels suggest a more complex type of placental pathology. They have stronger association with pregnancy complications including: late fetal loss, gestational hypertension, preeclampsia, IUGR, preterm delivery and IUFD. CONCLUSIONS: Mid-trimester maternal serum hCG or AFP levels alone cannot detect all pregnant women with increased risk to develop pregnancy complications. Multiparameter testing of placental function in mid-trimester (maternal serum hCG and AFP screening, uterine artery Doppler and placental morphology) may allow us to identify women with increased risk to develop severe placental insufficiency and pregnancy complications. However, future prospective studies are needed to confirm the prognostic significance of multiparameter testing of placental function in mid-trimester.

Vaginal primary malignant melanoma: a rare and aggressive tumor.

Vaginal primary malignant melanoma is a rare and very aggressive tumor. It most commonly occurs in postmenopausal women, with a mean age of 57 years. Our patient is an 80-year-old, postmenopausal Greek woman presented with a complaint of abnormal vaginal bleeding. On gynecologic examination there was a pigmented, raised, ulcerated, and irregular lesion 5 × 4.5 cm in the upper third of anterior vaginal wall. She underwent a wide local excision of the lesion. The histopathology revealed vaginal primary malignant melanoma with ulceration and no clear surgical margins. She denied any additional surgical interventions and underwent to postoperative adjuvant radiotherapy. Follow up 5 months after initial diagnosis revealed no evidence of local recurrence or distant metastasis. The prognosis of vaginal primary malignant melanoma is very poor despite treatment modality, because most of the cases are diagnosed at advanced stage. Particularly patients with no clear surgical margins and tumor size >3 cm needed postoperative adjuvant radiotherapy.

Expression and potential role of ErbB receptors in type II endometrial cancer.

OBJECTIVE: Endometrial cancer is the most common malignancy of the female genital tract. Based on clinical and pathological features, endometrial cancer is classified into two types. The aim of our study was to describe the expression and the potential clinical role of ErbB receptors in Greek patients with type II endometrial cancer. STUDY DESIGN: Between 1991 and 2008, 10 women with histologically confirmed type II endometrial cancer were referred to the Department of Gynecologic Oncology of the University of Patras Medical School. Tissue specimens from endometrial lesions were immunostained for EGFR, ErbB-2, ErbB-3 and ErbB-4. RESULTS: For EGFR, 5 cases were positive (50%) and 5 cases were negative. For ErbB-2, 9 cases were positive (90%) and 1 case was negative. For ErbB-3, all cases were positive. For ErbB-4, 7 cases were positive (70%) and 3 cases were negative. Also for all ErbB receptors, 5 cases were positive (50%). During follow up, 3 patients died from their disease. All of them had papillary serous endometrial cancer and 2 of them were positive for all ErbB receptors. CONCLUSION: Although our study was based on a small number of cases, it is obvious that we had high expression levels of ErbB receptors in patients with type II endometrial cancer. Also the majority of patients with dismal outcome were positive for all ErbB receptors. This is very important, as ErbB-targeted therapies may be clinically active as adjuvant therapy in well-defined subgroups of type II EC patients with EGFR and ErbB-2 overexpression.

Systemic Sclerosis and Multiple Cancers of the Female Genital Tract: Prolonged Survival following Current Treatment Strategies.

Background. Systemic sclerosis is a rare, chronic, multisystem, and autoimmune disease. There is an overall increased risk of malignancy in patients with systemic sclerosis. However, multiple cancers of the female genital tract in patients with SSc are a very rare event. Our aim is to present a case of SSc and multiple cancers of the female genital tract, with prolonged survival following current treatment strategies. Case. The patient, a 43-year-old nulliparous premenopausal Greek woman suffering from systemic sclerosis, presented with a history of abdominal pain and abnormal uterine bleeding. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, total omentectomy, appendectomy, and pelvic lymph node dissection. The histopathology revealed synchronous primary cancers of the endometrium and left ovary. The final diagnosis was stage Ib endometrial cancer endometrioid type and stage IIIc ovarian cancer endometrioid type. She underwent postoperative adjuvant chemotherapy and remains well without evidence of disease 89 months after initial surgery. Conclusion. Although our patient was diagnosed at advanced stage disease, prolonged survival may be related with radical surgery and postoperative adjuvant chemotherapy according to current treatment strategies.

Percutaneous minimally invasive management of iatrogenic ureteral injuries.

PURPOSE: To present experience with the percutaneous management of iatrogenic ureteral injuries. PATIENTS AND METHODS: Eighteen women and six men with a mean age of 59.3 years (range 33-80 years) received a diagnosis of ureteral injury sustained during gynecologic, urologic, and general surgical procedures. In a total of 25 injured ureters, 12 had interruption of continuity of their lumen, 10 were associated with contrast extravasation, and 3 were related to both. A standard percutaneous nephrostomy tract was established on the side of the afflicted kidney. Combined use of hydrophilic guidewires and balloon dilations were performed to achieve antegrade recanalization of the ureteral lesion. Then, a ureteral stent was inserted to assure patency. RESULTS: Average stricture length was 1.21 (range 0.5-1.9 cm). Success of the aforementioned technique was possible in 18 ureters. Successful management in one session took place in 14 ureters. Average hospitalization time was 1.8 days (range 0-5 d). The follow-up period ranged between 12 and 18 months, with mean follow-up time of 12.9 months. Ureteral patency was evident at 1 week follow-up in six patients with obstructed ureters. In the remaining patients, balloon dilation of the stricture was repeated, and another stent was placed. Extravasation of contrast was observed in two patients with extravasating ureters in the same period. Nephrostomy tubes were removed after a mean indwelling period of 5.9 weeks (range 1-12 wks). Two patients treated by the described method died during their hospitalization in the intensive care unit because of sepsis from peritonitis that was related to colon injury and multiple concomitant injuries. Major complications were not observed in the remaining 22 patients during the follow-up period. CONCLUSION: The minimally invasive management of ureteral injuries is a safe and efficient method for both ureteral obstruction and/or laceration in a wide range of iatrogenic ureteral injuries.

Sarcoidosis of the vulva: a case report.

Sarcoidosis of the vulva is a very rare condition. Until now, only four cases have been reported in English literature. The patient, a 48-year-old, gravid 3, para 2 postmenopausal Greek woman presented with a 6 months history of perineal pain. The patient underwent a wide local excision of the painful lesion. The histology revealed sarcoidosis of the vulva. She remains well without evidence of relapse 12 months after operation.