Metastatic neoplasms of the ovaries: a clinicopathological study of 97 cases.

OBJECTIVE: To present the clinicopathological features of metastatic ovarian neoplasms with emphasis in the diagnostic challenge. METHODS: This is a retrospective study including 97 patients with pathological diagnosis of metastatic ovarian neoplasms, examined during the decade 2000-2009. The gross, microscopical and immunohistochemical characteristics as well as the clinical data (age of the patients, origin of the neoplasm, symptoms, treatment options) and 5-year survival rates were examined. RESULTS: The mean age of the patients is 55 years (range 26-78 years). 62.89% of the tumors were metastatic from extragenital organs (from stomach 21.65%, breast 15.46%, colon 15.46%, appendix 3.09%, pancreas 2.06%, lung 1.03% and kidney 1.03%, sarcoma 1.03% melanoma 1.03%) and 37.11% tumors originated from the genital tract. The 3-year survival rates ranged from 25.39% for metastatic ovarian neoplasms originating outside the genital tract up to 29.41% for those originating from the genital tract. Tumor immunohistochemistry is a helpful aid in the differential diagnosis mainly between primary mucinous ovarian tumors and metastatic colon cancers and in the recognition of metastatic breast cancers and other neoplasms of the GI tract. CONCLUSION: The management of metastatic ovarian neoplasms should include specific immunohistochemical methods in order to identify the primary neoplasm site. The differential diagnosis of a pelvic mass should always include metastatic neoplasms of the ovaries.

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.

Clinical value of preoperative lymphoscintigraphy in patients with early cervical cancer considered for intraoperative lymphatic mapping.

UNLABELLED: The purpose of this study was to examine the clinical usefulness of preoperative lymphoscintigraphy (PLS) for sentinel node identification in patients undergoing lymphatic mapping during surgery for early cervical cancer. PATIENTS AND METHODS: Day-before PLS was performed in 42 patients who were candidates for open radical hysterectomy and intraoperative lymphatic mapping, using a combination of radiocolloid and blue dye technique. RESULTS: In 39 patients, at least one sentinel node (SN) was evident either in the lymphoscintigram or during the operation (detection rate 92.8%). Lymphoscintigraphy revealed unilateral SNs in 24 (61.5%) cases and bilateral SNs in 15 (38.5%). A total of 56 SNs were identified. Intraoperatively, 5 out of 24 patients with unilateral SNs on PLS had bilateral identification. The total number of SNs retrieved was 103 (2.6/patient). While one SN was identified in 25 cases on PLS, 32 patients had two or more SNs intraoperatively. The agreement between preoperative and intraoperative detection regarding laterality, number and location of SNs was poor (Kappa<0.69). CONCLUSION: PLS is of limited clinical value for intraoperative SN detection in early cervical cancer.

Resveratrol activation of nitric oxide synthase in rabbit brain synaptosomes: singlet oxygen (1O2) formation as a causative factor of neurotoxicity.

In the present study it was shown that resveratrol (3,4,5-trihydroxystilbene), an efficient light-absorbing molecule, during its transition from trans to cis configuration under UV light, transfers its energy of excitation to triplet oxygen to produce singlet oxygen ((1)O(2)). This transition is prevented by Trolox, a quencher of singlet oxygen. In the presence of a stable amount of nitrosoglutathione, UV-irradiated resveratrol reacts with nitric oxide (NO) originating from the nitrosoglutathione to produce peroxynitrite (ONOO(-)). Beta-carotene, acting as a quencher of (1)O(2), prevents the transition of resveratrol from trans to cis. Beta-carotene also prevents DNA damage induced by the (1)O(2). NO synthase (NOS) activity in synaptosomes isolated from rabbit brain increased approximately three-fold by resveratrol and the NO released was converted to ONOO(-). Resveratrol increased the lipid fluidity of synaptosomal plasma membranes. These changes suggest that the incorporation of resveratrol into synaptosomal plasma membranes causes an up-regulation of NO synthase. On the other hand, the simultaneous ONOO(-) and (1)O(2) formation may cause disturbances in transmembrane signal transduction leading to neurotoxicity. The present study concerning the behavior of resveratrol with respect to its structure and potential prooxidant-antioxidant function provides important new clues as to the role of this fascinating molecule in pathophysiology.

Complete pelvic lymphadenectomy in patients with clinical early, grade I and II endometrioid corpus cancer.

AIM: To investigate the risk of pelvic lymph node metastasis in patients with a preoperative diagnosis of early endometrial cancer with favorable histological characteristics, assessed by complete pelvic lymphadenectomy. PATIENTS AND METHODS: A total of 108 patients with clinical early endometrioid grade I or II endometrial carcinoma underwent complete pelvic lymphadenectomy between 2001-2007. Only cases with at least 15 nodes histologically examined were included. All operations were performed by the same team. The preoperative tumor histology was compared with the final pathological findings. The incidence of pelvic nodal involvement was estimated in relation to the final grade and depth of myometrial invasion in halves. RESULTS: The median age of patients was 63 years. In the final histology, 10 tumors (9.3%) of non-endometrioid histology were found. The discordance between pre- and postoperative tumor grade was 32.4%, with 24.1% being upgraded. Nine patients (8.3%) had poorly differentiated tumors and 23 (21.3%) deep (>50%) myometrial invasion in the final pathology. A total of 11 patients (10.2%) had pelvic nodal metastasis. The rate of lymph node metastasis in relation to final grade I and II and myometrial invasion was as follows: grade I, 1.8% (inner half 0%, outer half 14.3%); grade II, 15.9% (inner half 12.1% outer half 27.3%). Overall 19.4% of patients were upstaged at surgery. CONCLUSION: A significant proportion of patients presenting with early endometrial cancer of optimal characteristics will have a more advanced disease at surgical staging. Complete pelvic lymphadenectomy may increase the possibility of detecting metastatic disease in the lymph nodes.

The sentinel node in cervical cancer patients: role of tumor size and invasion of lymphatic vascular space.

BACKGROUND: The sentinel lymph node (SLN) technique aims at predicting the absence of regional nodal metastasis and seems promising in the management of cervical cancer patients. PATIENTS AND METHODS: Forty patients undergoing surgery for early cervical cancer were submitted to the SLN procedure, using Blue Patente alone in 3, radiocolloid injection alone in 4 and both methods in 33 (82.5%). All patients underwent radical hysterectomy and pelvic lymphadenectomy. RESULTS: The detection rate was as follows: overall 85%, blue dye alone 66%, radiocolloid alone 75%, dual method 87%. Detection was successful in 34 patients, with one false-negative result. No micrometastases were demonstrated during ultrastaging of the sentinels. The detection rate was higher in tumors <2 cm (94.1%) than in larger tumors (78.2%, p>0.09). Significant negative correlation between lymphatic vascular space invasion (LVSI) and detection rate was found (p<0.001). CONCLUSION: SLN detection is feasible in early cervical cancer but presence of LVSI and a tumor size >2 cm negatively affect the detection rate and may increase the incidence of false negatives.

Formation of heme-iron complexes with nitric oxide (NO) and peroxynitrite (ONOO-) after ultraviolet radiation as a protective mechanism in rat skin.

Ultraviolet C (UVC)-irradiated microvessels isolated from rat skin release free nitrogen radicals, i.e. nitric oxide (NO), peroxynitrite (ONOO-) and nitrosocompounds formed from L-arginine. During UVC radiation of microvessels, heme (Fe3+) is released from hemoglobin and reacts with NO to form nitrosyl-heme (Fe2+-NO). The hydroxyl radical (OH*) produced is attached to heme-iron (Fe3+) to form hematin. ONOO- then binds to Fe(OH) and the complex Fe[(OH)ONOO-]2- is formed. Thus, in cases of increased oxidative stress, the free heme can act as an endogenous scavenger of OH* and ONOO-. Furthermore, Fe-NO and Fe[(OH)ONOO-]2- can act as NO donor and as antioxidant in redox cyclic iron-centered heme reactions, respectively. The scavenging-antioxidant properties of heme complexes, which allow it to protect the cells from the cytotoxic effects of the oxygen and/or nitrogen free radicals, were verified by estimating the changes in membrane fluidity of microvessels after UVC radiation. The present study indicates that UVC radiation of the skin acts as a potent stimulator for the formation of Fe-NO and Fe[(OH)ONOO-]2- in microvasculature with cytoprotective effects.

Secondary cytoreductive surgery in patients presenting with isolated nodal recurrence of epithelial ovarian cancer.

OBJECTIVES: To evaluate the role of secondary cytoreductive surgery in the management of patients with isolated nodal recurrence of epithelial ovarian cancer. METHODS: In this retrospective study, the data of 21 patients submitted to secondary cytoreductive surgery for isolated nodal recurrence were reviewed. All clinical characteristics at initial treatment and relapsing disease, operative and pathologic data of secondary cytoreduction and follow-up information were abstracted from the files and evaluated. RESULTS: Median age at initial treatment was 50 years; 15 patients (71%) had FIGO stage III/IV disease. Following primary surgical and systematic treatment, isolated nodal recurrence was diagnosed after a median DFI of 21 months (range 8-156). Location of nodal disease was pelvic in 4, paraaortic in 8, pelvic plus paraaortic in 4, inguinal in 4 and in the axilla in 1 of the patients. Median tumor size was 3 cm. CA-125 levels >35 U/ml were present in 13 cases. Complete cytoreduction was achieved in 17 (81%) and optimal (

Treatment of early uterine sarcomas: disentangling adjuvant modalities.

Uterine sarcomas are a rare group of neoplasms with aggressive clinical course and poor prognosis. They are classified into four main histological subtypes in order of decreasing incidence: carcinosarcomas, leiomyosarcomas, endometrial stromal sarcomas and "other" sarcomas. The pathological subtype demands a tailored approach. Surgical resection is regarded as the mainstay of treatment. Total abdominal hysterectomy and bilateral salpingo-oophorectomy represents the standard treatment of uterine sarcomas. Pelvic and para-aortic lymph node dissection in carcinosarcomas is recommended, given their high incidence of lymph node metastases, and may have a role in endometrial stromal sarcomas. Adjuvant radiation therapy has historically been of little survival value, but it appears to improve local control and may delay recurrence. Regarding adjuvant chemotherapy, there is little evidence in the literature supporting its use except for carcinosarcomas. However, more trials are needed to address these issues, especially, their sequential application. Patients with uterine sarcomas should be referred to large academic centers for participation in clinical trials.

Intraoperative gross assessment of myometrial invasion and cervical involvement in endometrial cancer: Role of tumor grade and size.

OBJECTIVES: To evaluate the accuracy of visual examination of myometrial invasion and the involvement of the cervix in the hysterectomy specimen and to explore the role of tumor grade and size in the accuracy of gross estimation of myometrial invasion. METHODS: In 142 patients with apparent early endometrial cancer the uterus was opened after its removal and inspected. The size of the tumor (2 cm), the depth of myometrial invasion (less or greater than 50%) and the involvement of the cervix (as positive or negative) were visually estimated and recorded. All patients underwent surgical staging. The gross findings were compared with the final histological results. Estimations of myometrial invasiveness were analyzed according to the tumor grade and size. Accuracy, specificity, sensitivity, positive and negative predictive values were calculated. RESULTS: The overall accuracy rate for myometrial invasion was 81.7% (116/142). False positive and false negative results noted in 17/101 (17%) and 9/41 (21.9%) of patients. Sensitivity, specificity, positive and negative predictive values were 78%, 83.2%, 65.3% and 90.3% respectively. Gross estimation of invasion was more often successful in patients with smaller (

Cathepsin B protein levels in endometrial cancer: Potential value as a tumour biomarker.

OBJECTIVE: Lysosomal cysteine protease Cathepsin-B has been implicated in the progression of various human tumours. We examined Cathepsin-B protein levels in endometrial carcinoma patients-mainly post-menopausal-and investigated their possible association with clinical and pathological parameters in order to assess Cathepsin-B's significance as a potential tumour biomarker. METHODS: The indirect immunoperoxidase method was used for Cathepsin-B immunohistochemical staining of 64 paraffin-embedded endometrial tumour tissues, having follow-up period of 18-240 months. Steroid hormone receptors were measured as well. Tissue samples were staged following the FIGO criteria. RESULTS: Positive Cathepsin-B immunostaining was observed in 27 patients (42.2%) and was significantly associated with the FIGO stage of the disease (p=0.006), as well as cervical and stromal invasion (p=0.001 and p=0.037, respectively) and progesterone receptor status (p=0.027). Positive Cathepsin-B expression was also inversely related to Disease-free Survival (p=0.034) and Overall Survival (p=0.035) in univariate analysis, as well as in multivariate analysis (p=0.022 and p=0.035, respectively). CONCLUSION: Increased Cathepsin-B expression was found to be predictive of more aggressive tumour behaviour over time and can be regarded as an unfavourable and independent tumour marker for endometrial cancer patients with a long follow-up.

Juvenile granulosa cell tumor associated with pregnancy: Report of a case and review of the literature.

BACKGROUND: Juvenile granulosa cell tumors account for about 5% of all granulosa cell tumors and are diagnosed in nearly 80% of cases during the first two decades of life. Only 10% of granulosa cell tumors present during pregnancy. The incidence of ovarian malignancies during pregnancy varies from 0.05 to 0.07 per 1000 pregnancies. CASE: A 31-year-old pregnant woman was admitted to our university hospital due to an adnexal mass, 9.5 cm in diameter, which was detected at 34 weeks of gestation. At 37 + 5 weeks of gestation, a cesarean section with right salpingo-oophorectomy and removal of the tumor was performed. Histopathological findings, including immunohistochemical study, led to the diagnosis of juvenile granulosa cell tumor (JGCT). CONCLUSION: The histological features and the differential diagnosis of the JGCT are discussed. The optimal management of such adnexal masses during pregnancy is also discussed. A JGCT that is confined to the ovary appears to have an excellent prognosis and can be treated by unilateral salpingo-oophorectomy.

Determination of cathepsin B expression may offer additional prognostic information for ovarian cancer patients.

The lysosomal cysteine proteinase cathepsin B has been implicated in the progression of various human tumors including ovarian cancer. Included in this study were 63 patients with epithelial ovarian carcinoma. Follow-up information (median follow-up period 7 years) was available for all patients, among whom 42 (66.7%) had relapsed and 32 (50.8%) had died. The immunohistochemistry method was adopted for the detection of cathepsin B using paraffin embedded specimens. Results were compared to clinico-pathological data. Statistical analysis showed cathepsin B expression to be significantly associated with the stage of disease, debulking success and interestingly, with progesterone receptors. It was also inversely related to progression-free survival (PFS) and overall survival (OS). Accordingly, cathepsin B can be regarded as unfavorable and as an independent tumor marker for progression-free survival and overall survival in ovarian cancer patients with long follow-up.