Depressive symptoms during adverse economic and political circumstances: A comparative study on Greek female breast cancer patients receiving chemotherapy treatment.

The aim of this study was to search for an effect of the adverse economic and political events that took place in 2015 in Greece (threat of bankruptcy, referendum, capital controls) on depressive symptoms of breast cancer patients on chemotherapy. The clinician-rated version of the Inventory of Depressive Symptomatology (IDS-C30) and a form documenting sociodemographic, medical and social network characteristics were administrated in two groups of patients: one in 2010 and one in the aftermath of the July 2015 events. No differences were found between medical, demographic and social characteristics. The IDS-C30 median value of patients treated in 2010 was 28.07 (CI, 25.91-31.60), while that of the 2015's group was 18.00 (CI, 16.92-20.60), indicating less depressive symptoms for the second group. The analysis revealed that the differences between the two groups were statistically significant (p = <.001), denoting a strong effect size (r = .53). Lower depressive symptoms after the July 2015 events could be explained by different personal and social factors- most possibly an increase of social support to the most vulnerable-yet to be proven. Future research on the effect of striking economic and political events on mental health of a larger cohort of breast cancer patients is warranted.

High prevalence of BRCA1 founder mutations in Greek breast/ovarian families.

We have screened 473 breast/ovarian cancer patients with family history, aiming to define the prevalence and enrich the spectrum of BRCA1/2 pathogenic mutations occurring in the Greek population. An overall mutation prevalence of 32% was observed. Six BRCA1 recurrent/founder mutations dominate the observed spectrum (58.5% of all mutations found). These include three mutations in exon 20 and three large genomic deletions. Of the 44 different deleterious mutations found in both genes, 16 are novel and reported here for the first time. Correlation with available histopathology data showed that 80% of BRCA1 carriers presented a triple-negative breast cancer phenotype while 82% of BRCA2 carriers had oestrogen receptor positive tumours. This study provides a comprehensive view of the frequency, type and distribution of BRCA1/2 mutations in the Greek population as well as an insight of the screening strategy of choice for patients of Greek origin. We conclude that the Greek population has a diverse mutation spectrum influenced by strong founder effects.

Germ line BRCA1 & BRCA2 mutations in Greek breast/ovarian cancer families: 5382insC is the most frequent mutation observed.

BRCA1 and BRCA2 genes were screened for loss-of-function mutations in a series of 85 patients having at least one first- or second-degree relative affected by breast and/or ovarian cancer. All BRCA1 exons and BRCA2 exons 10 and 11 were screened with a combination of methods including SSCP, PTT and direct sequencing. We have found disease-associated mutations in 14 families (16.5%), eleven in BRCA1 and three in BRCA2. The known founder mutation 5382insC of BRCA1 was identified in seven unrelated families. The other mutations identified include the non-sense R1751X, the splice junction variant 5586G>A of BRCA1 and three frameshifts, 2024del5, 3034del4, and 6631del5, of BRCA2. Nine out of these 14 families had a family history of three or more breast/ovarian cancer cases. A large number of polymorphic or unclassified variants is also reported. Combined with our previously published data 5382insC was found in nine out of 20 families (45%), suggesting that this mutation may represent a common founder mutation in the Greek population.

BRCA1 mutation analysis in breast/ovarian cancer families from Greece.

Germline mutations in BRCA1 gene account for varying proportions of breast/ovarian cancer families, and demonstrate considerable variation in mutational spectra coincident with ethnic and geographical diversity. We have screened for mutations the entire coding sequence of BRCA1 in 30 breast/ovarian cancer women with family history of two or more cases of breast cancer under age 50 and/or ovarian cancer at any age. Genomic DNA from patient was initially analyzed for truncating mutations in exon 11 with PTT followed by DNA sequencing. In the cases where no frameshift mutation was observed in exon 11, all other exons were screened with direct sequencing. Two novel (3099delT, 3277insG) and three already described (3741insA, 1623del5-TTAAA, 5382insC-twice) truncating mutations were identified. In addition, 6 point mutations (L771L, P871L, E1038G, K1183R, S1436S, S1613G) which are already classified as polymorphisms were identified. Three unclassified intronic variants (IVS16-68 G>A, IVS16-92 G>A, IVS18+65G>A) were also detected. These results show that BRCA1 deleterious mutations are present in a fraction (20%) of Greek breast/ovarian cancer families similar to other European countries. Mutations were detected in high- (>/=3 members) as well as in moderate-risk (2 members) families. This is the first report of BRCA1 mutation analysis in Greece.

Mammary fibroblasts may influence breast tumor angiogenesis via hypoxia-induced vascular endothelial growth factor up-regulation and protein expression.

Recent studies demonstrate the relationship of microvessel density to malignant progression in breast cancer (N. Weidner, J. P. Semple, W. R. Welch, and J. Folkman, N. Engl. J. Med., 324: 1-8, 1991), underscoring the importance of angiogenesis in this tumor. Crucial in tumor angiogenesis are the paracrine actions of tumor-secreted factors (e.g., vascular endothelial growth factor), which have been thought to derive from the tumor epithelial cells themselves. We demonstrate that in response to hypoxic conditions, human mammary fibroblasts dramatically up-regulate vascular endothelial growth factor mRNA and increase vascular endothelial growth factor protein levels in accordance with the degree of oxygen deprivation. Thus, mammary stromal cells, only recently considered in the regulation of breast carcinomas, may play a hitherto unrealized role in breast cancer angiogenesis.

Ovarian tumors: prediction of the probability of malignancy by using patient's age and tumor morphologic features with a logistic model.

An attempt was made to predict the probability of malignancy of a given ovarian tumor in a certain patient by using the age and simple morphologic features of the tumor. A cohort of 959 patients with ovarian tumors was analysed retrospectively according to the patient's age and tumor characteristics such as greatest diameter, consistency, bilaterality and diagnosis as malignant (271 patients) or benign (688 patients). All variables were entered unconditionally in a logistic regression. The presence of solid/multilocular elements has a 9.6-fold increased risk of malignancy, where a bilateral tumor has a 2.8-fold increase. Significant increase in risk of malignancy was observed in ages under 20 and over 40 years, as well as in tumors with a diameter larger than 9 cm. All variables were highly significant associated with the discrimination between benign and malignant. A formula including all variables has been developed so that the probability of malignancy can be estimated by a scientific calculator. In conclusion, simple, easily determined by ultrasound and reproducible criteria such as patient's age, tumor size, consistency and bilaterality were assembled in a logistic model in order to predict the probability of malignancy for a given ovarian tumor, in an individual patient.

Arm morbidity following treatment of breast cancer with total axillary dissection: a multivariated approach.

In order to clarify the factors that mainly influence arm morbidity following treatment of breast cancer with the full axillary dissection protocol, we evaluated, in a model of multiple regression analysis, parameters such as the type of breast surgery, adjuvant radiotherapy, time of irradiation, age, number of dissected nodes and axillary nodal status. A total of 104 women were studied. Late arm edema was observed in 17% of the patients and was more frequent when (1) irradiation was given immediately after the operation than if it was given 6 months later (p = 0.009) and (2) the number of removed nodes exceeded 40 (p = 0.037). Upper limb pain was reported by 16% of the patients and was reported more frequently from patients over 60 years of age (p = 0.036), as well as from patients who underwent modified radical mastectomy (p = 0.044) and those in whom 30-40 nodes were dissected (p = 0.025). Shoulder joint mobility was impaired in 17% of the patients, and it was not affected by any of the examined factors. It seems that conservative breast surgery or adjuvant breast radiotherapy 6 months after the operation might reduce independently the likelihood of arm morbidity by 25%.

Pelvic surgery, reproductive factors and risk of ectopic pregnancy: a case controlled study.

A case controlled study among 361 women with surgically treated ectopic pregnancy and 420 women delivered at term was designed, aiming at characterization of the association among previous pelvic operations, selected reproductive factors and ectopic pregnancy. All types of previous pelvic operations increase the risk of ectopic pregnancy from a 2-fold increase for appendectomy to a 9-fold increase for ectopic pregnancy, if maternal age, parity, history of spontaneous and induced abortions and history of infertility is controlled. This study suggests that a previous pelvic operation may increase the risk of ectopic pregnancy.

Labor characteristics of uncomplicated prolonged pregnancies after induction with intracervical prostaglandin E2 gel versus intravenous oxytocin.

Labor characteristics after intracervical application of 0.5 mg prostaglandin (PG) E2 gel (n = 83) versus intravenous administration of oxytocin (n = 82) for labor induction were investigated in uncomplicated prolonged pregnancies with unripe cervix. The induction to delivery time as well as the total oxytocin dose were significantly reduced in the PGE2 group (p < 0.001). Cesarean sections, instrumental deliveries and fetal distress had the same frequency, but the failures of trial were significantly higher in the oxytocin group than in the PGE2 group (20.7 vs. 6%, p < 0.01). Twenty-four percent of women needed a second PGE2 dose, and almost half of the women in the PGE2 group experienced 'spontaneous' labor. More neonates in the oxytocin group had 5-min Apgar scores < 7 (p < 0.05). Intracervical PGE2 gel application is superior to intravenous oxytocin in terms of shortening the induction-delivery interval and increasing the frequency of successful vaginal delivery. In addition, it is safe for mother and fetus.

PIP: Labor characteristics after intracervical application of 0.5 mg prostaglandin E2 (PGE2) gel (n=83) vs iv administration of oxytocin (n=82) for labor induction were investigated in uncomplicated prolonged pregnancies with unripe cervix. The induction-to-delivery time as well as the total oxytocin dose were significantly reduced in the PGE2 group (p0.001). Cesarean sections, instrumental deliveries, and fetal distress occurred with the same frequency, but the failures of trail were significantly higher in the oxytocin group than in the PGE2 group (20.7 vs 6%, p0.01). 24% of the women required a 2nd dose of PGE2, and almost 1/2 of the women in the PGE2 group experiences spontaneous labor. More neonates in the oxytocin group had 5-minute Apgar scores 7 (p0.05). Intracervical PGE2 gel application is superior to iv oxytocin in terms of shortening the induction-to-delivery interval and increasing the frequency of successful vaginal delivery. In addition, it is safe for both mother and fetus.

Expression of carcinoembryonic antigen and ferritin in normal, hyperplastic, and neoplastic endometrium.

The distribution of carcinoembryonic antigen (CEA) and ferritin was demonstrated by immunohistochemical method in 95 patients with normal, hyperplastic, and neoplastic endometrium in order to distinguish among these conditions. Fifteen patients with normal endometrium (NE), 28 with hyperplasia (AH), 12 with atypical hyperplasia (AAH), and 40 with endometrial carcinoma (CA) were studied. Paraffin section tissues were subjected to immunostaining according to the avidin-biotin complex method. CEA was found in 33% of NE cases, 46% of AH, 75% of AAH, and 83% of CA (P less than 0.01). Ferritin was not detected in any case of NE; however, it was detected in one case (4%) of AH, in one case (8%) of AAH, and in 88% of CAs (P less than 0.001). Both tumor markers exhibited a heterogeneous staining pattern, and for a given histologic hyperplastic or malignant lesion, corresponded to several phenotypes. There was no significant correlation between clinical stage or tumor grade and CEA or ferritin expression. In conclusion, ferritin seems to be a better biological marker than CEA in distinguishing between hyperplastic and neoplastic endometrial lesions and it is also more reliable than CEA for endometrial malignancy since it was absent in normal and hyperplastic endometria.

Late midtrimester medical pregnancy terminations: three different procedures with prostaglandin F2 alpha and laminaria tents.

One hundred twenty eight women underwent midtrimester induced abortion with: 1) combined regimen of intramniotic prostaglandin (PG) F2a injection and intracervical laminaria tents (group A, 50 women), 2) intramniotic PGF2a injection only (group B, 51 women) and 3) laminaria tents followed by intracervical PGF2a tablets insertion (group C, 27 women). The mean induction-abortion time (+/- SE) was 24.9 +/- 1.7 hours for group A, 28.2 +/- 2.2 hours for group B (p greater than 0.05) and 42.1 +/- 3.4 hours for group C, significantly longer than goup A and B (p less than 0.001 and p less than 0.01 respectively). In 48 hours 98% of the patients of group A, 90% of group B (p less than 0.05) and 59% of group C (p less than 0.001) completed the abortion procedure. Parous women of group A and B presented similar induction - abortion time, while in nulliparous the use of laminaria shortened the abortion procedure significantly (p less than 0.05). The complications rate was low. In conclusion, the intracervical PGF2a insertion is a simple but very slow abortion procedure with high failure rates. The intramniotic PGF2a injection is a successful method for late midtrimester medical pregnancy termination and the concurrent use of laminaria tents shortens the abortion procedure, particularly in nulliparous, reduces the number of prostaglandins' reinjections and increases the incidence of successful abortion within 48 hours.

PIP: 128 women underwent midtrimester induced abortion with the following: 1) a combined regimen of intraamniotic prostaglandin F2alpha (PGF2alpha) injection and intracervical laminaria tents (group A, 50 women); 2) intraamniotic PGF2alpha injection only (group B, 51 women); and 3) laminaria tents followed by intracervical PGF2alpha tablets insertion (group C, 27 women). The mean induction-abortion time (+or -SE) was 23.9 +or-1.7 hours for group A, 28.2 +or-2.2 hours for group B (p0.05), and 42.1 +or-3.4 hours for group C, which was significantly longer than groups A or B (p0.001 and p0.01). In 48 hours, 98% of the patients in group A, 90% of group (p0.05), and 59% of group C (p0.001) completed the abortion procedure. Parous women in groups A and B presented similar induction-abortion time, while among nulliparous women, the use of laminaria shortened the abortion procedure significantly (p0.05). The complications rate was low. In conclusion, the intracervical PGF2alpha insertion is a simple but very slow abortion procedure with high failure rates. The intraamniotic PGF2alpha injection is a successful method for late midtrimester medical pregnancy termination and the concurrent use of laminaria tents shortens the abortion procedure, particularly in nulliparous women, reduces the number of PG reinjections, and increases the incidence of successful abortion within 48 hours.

Clinical evaluation of a sensitive urine pregnancy test in the gynecological emergencies.

A rapid sensitive urine pregnancy test (SPT) using monoclonal antibody against human chorionic gonadotropin and a conventional urine pregnancy test (GPT) were performed in 364 women attending 'Gynecological Emergencies' for lower abdominal pain and/or vaginal bleeding, aiming at early detection of ectopic and intra-uterine pregnancy-related disorders. The overall incidence of a positive test was 24%. In 42 patients, with histopathological evidence of ectopic pregnancy, SPT was positive in 41 (98%), while GPT only in 19 (45%). In 47 patients with evidence of intra-uterine pregnancy-related disorders, SPT was positive in 45 (96%), while GPT in 33 (70%). The sensitive urine pregnancy test can improve significantly the efficiency of the early diagnosis of ectopic and intra-uterine pregnancy-related disorders, and can be used as a screening method for patients having even in the slightest way suspect of having an ectopic pregnancy.

Value of immunohistochemical demonstration of several epithelial markers in hyperplastic and neoplastic endometrium.

The distribution of prekeratin, vimentin, epithelial membrane antigen (EMA), and secretory component (SC) was demonstrated immunohistochemically in 31 patients with adenomatous hyperplasia (AH), 12 patients with atypical adenomatous hyperplasia (AAH), and 39 patients with endometrial carcinoma. Prekeratin was presented in 94% of AHs, 92% of AAHs, and 87% of adenocarcinomas. Vimentin was detected in 68% of AHs, 50% of AAHs, and 37% of adenocarcinomas, showing decreased expression as the lesion progressed to malignancy (P less than 0.05). EMA was detected in 26% of AHs, 67% of AAHs, and 95% of adenocarcinomas (P less than 0.001). SC demonstrated focal and weak expression in 29% of AHs, but showed increased staining intensity in 67% of adenocarcinomas (P less than 0.01). Well-differentiated tumors expressed SC better than poorly differentiated tumors (P less than 0.01). All markers showed a heterogeneous staining pattern and, for a given histologic hyperplastic or neoplastic state, corresponded to several phenotypes. In conclusion, prekeratin seems to be a good marker for epithelial differentiation in hyperplastic endometrium, and EMA is a good marker in neoplastic endometrium. In hyperplastic lesions, the loss of vimentin expression in the absence of secretory changes gives rise to suspicions regarding their benign process. Also, EMA can help in distinguishing between hyperplastic and neoplastic states, while detection of SC may be of help in more precise grading of endometrial carcinoma.