Adjuvant chemotherapy in patients with stage I endometrioid or clear cell ovarian cancer in the platinum era: a Surveillance, Epidemiology, and End Results Cohort Study, 2000-2013.

BACKGROUND: We sought to evaluate the impact of adjuvant chemotherapy on overall survival (OS) in patients with stage I endometrioid epithelial ovarian cancer (EEOC) or ovarian clear cell cancer (OCCC) using a national database. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results database was used to identify patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I EEOC or OCCC from 2000 to 2013. We sought to identify predictors of chemotherapy use and to assess the impact of chemotherapy on OS in these patients. OS was compared using the log-rank test and the Cox proportional hazards model. RESULTS: In all, 3552 patients with FIGO stage I EEOC and 1995 patients with stage I OCCC were identified. Of the 1600 patients (45%) with EEOC who underwent adjuvant chemotherapy, the 5-year OS rate was 90%, compared with 89% for those who did not undergo adjuvant chemotherapy (P = 0.807). Of the 1374 (69%) patients with OCCC who underwent adjuvant chemotherapy, the 5-year OS rate was 85%, compared with 83% (P = 0.439) for those who did not undergo adjuvant chemotherapy. Chemotherapy use was associated with younger age, higher substage, and more recent year of diagnosis for both the EEOC and OCCC groups. Only in the subgroup of patients with FIGO substage IC, grade 3 EEOC (n = 282) was chemotherapy associated with an improved 5-year OS-81% compared with 62% (P = 0.003) in untreated patients (HR: 0.583; 95% CI: 0.359-0.949; P = 0.030). In patients with OCCC, there was no significant effect of adjuvant chemotherapy on OS in any substage. CONCLUSIONS: Adjuvant chemotherapy was associated with improved OS only in patients with substage IC, grade 3 EEOC. In stage I OCCC, adjuvant chemotherapy was not associated with improved OS.

A review of the challenges faced in the conservative treatment of young women with endometrial carcinoma and risk of ovarian cancer.

OBJECTIVE: The standard management for women diagnosed with endometrial carcinoma (EC) is hysterectomy with salpingo-oophorectomy. However, more conservative treatment approaches, including uterine and ovarian preservation, may be used for women who have a strong desire to maintain fertility in spite of potential oncologic risks. METHODS: We reviewed the literature regarding fertility-preserving treatment for EC. We also conducted medical chart reviews for two young patients diagnosed with EC whose treatment deviated from the standard approach in order to preserve fertility. These patients were subsequently diagnosed with ovarian cancer. Our review summarizes the literature regarding the clinical and emotional implications of fertility preservation in young women. CASES: Two young nulliparous women (29 and 23 years, respectively) with grade 1 endometrioid adenocarcinoma were initially treated with conservative fertility-sparing endocrine therapy. Upon failure of endocrine treatment both women underwent hysterectomy and staging with ovarian preservation. During surveillance, both women were subsequently diagnosed with ovarian carcinoma and underwent bilateral salpingo-oophorectomy (BSO) and comprehensive staging. CONCLUSION: The management of young women with endometrial cancer can be complex and challenging. Patients and physicians are confronted with the dilemma of following standard surgical guidelines versus the desire to maintain fertility and avoid surgical menopause. Careful oncologic, psychotherapeutic, genetic and reproductive counseling is advised before offering a non-standard treatment strategy to young endometrial cancer patients.

Small cell neuroendocrine carcinoma of the cervix: Analysis of outcome, recurrence pattern and the impact of platinum-based combination chemotherapy.

OBJECTIVES: To analyze progression-free (PFS) and overall survival (OS) in patients with small cell neuroendocrine carcinoma of the cervix (SCNEC), and to determine whether platinum-based combination chemotherapy is beneficial for this population. METHODS: We performed a retrospective analysis of all patients with SCNEC who were treated at our institution between 1/1990 and 2/2007. Patients were excluded if pathologic diagnosis was not confirmed at our institution. Standard statistical methods were utilized. RESULTS: Seventeen patients met inclusion criteria. The estimated 3-year PFS and OS rates for the entire group were 22% and 30%, respectively. Median time to progression was 9.1 months. Extent of disease was the only significant prognostic factor. Median OS for patients with early stage disease (IA1-IB2) was 31.2 months and 6.4 months for patients with advanced stage disease (IIB-IV, P=0.034). In the early-stage disease group, the 3-year distant recurrence-free survival rate was 83% for patients who received chemotherapy and 0% for patients who did not receive chemotherapy as part of their initial treatment (P=0.025). The estimated 3-year OS rate was 83% for patients who received and 20% for patients who did not receive chemotherapy as part of their initial treatment (P=0.36). CONCLUSION: Given the rarity of SCNEC this retrospective analysis is limited by a small number of patients. However, the natural history of this rare disease is akin to small cell lung cancer and the prognosis is poor due to the tumor's propensity for distant spread. The treatment should conform to the treatment of small cell lung cancer.

[The impact of the pathologist on the treatment of epithelial ovarial cancer]. / Klinik des Ovarialkarzinoms und Erwartungen an den Pathologen.

The majority of patients with epithelial ovarian cancer (EOC) are diagnosed with advanced disease involving sites such as the upper abdomen, pleural space, and paraaortic lymph nodes. The standard therapy for advanced disease requires maximal cytoreductive surgery followed by postoperative platinum- and taxane-based chemotherapy. Despite maximal primary surgical effort and postoperative standard chemotherapy long-term survival of patients with advanced stage III or IV disease ranges from 30% to less than 10% due to early and late relapse or primary progressive disease. Facing the highly lethal nature of epithelial ovarian carcinoma, the clinical course of advanced disease is difficult to predict in an individual patient. This heterogeneity of clinical outcome in patients with ovarian carcinoma suggests that reliable prognostic and/or predictive factors would be of potential clinical value and new treatment options are warranted in the future. In the light of recently published studies we summarize the clinical features and the diagnostic, operative and postoperative management of epithelial ovarian carcinoma. We furthermore address the importance of the pathologist during the clinical course of patients with ovarian carcinoma. The issue of timing between surgery and chemotherapy in the setting of neoadjuvant chemotherapy treatment of advanced ovarian carcinoma is being highlighted as well as the significance of new diagnostic and therapeutic options with regard to accurate predictive markers, that might identify patients who are appropriate candidates for novel therapeutic approaches.

In search for predictive factors for atopy in human cord blood.

Since early prevention is regarded as an important corner stone in the management of atopic diseases, the identification of reliable markers detecting individuals at risk are of major interest. Therefore, many efforts have been made to unravel reliable predictors for atopy which might identify children at risk and allow the initiation of preventive strategies at an early stage. In the past, much scientific energy has been forced in particular on the development of as noninvasive methods as possible to reach this goal. It is obvious that the identification of markers for atopy at the earliest time of life - namely immediately after birth - represents one of the most attractive attempts. In consequence various studies have been initiated to address this issue investigating markers for atopy in cord blood. Most of them have been geared to our current knowledge about cellular and soluble factors which are dysregulated in adolescent atopic individuals. Although the findings of these studies will improve our knowledge about the initial evolution of atopy, several parameters evaluated did not show any association or have led to almost conflicting results. In order to provide an up-date about the current developments in this field, recent research findings on predictive factors for atopy in cord blood are summarized in the following synopsis.

3.0-T high-field magnetic resonance imaging of the female pelvis: preliminary experiences.

The purpose of this study was to evaluate if 3.0 T allows for clinically useful pelvic magnetic resonance imaging, i.e. if familiar image quality and tissue contrast can be achieved at 3.0 T as compared with at 1.5 T. Adapting a 1.5-T protocol to the 3.0-T environment is subject to a variety of factors. In order to reduce the number of potential variables, we chose two cornerstones: the 3.0-T sequence should have similar spatial resolution and acquisition time; furthermore, the contrast parameters repetition time (TR) and echo time (TE) were kept identical. Based on this modified 3.0-T T2-weighted turbo spin-echo sequence (TR/TE 2,705/80 ms; 0.7x1.04x4 mm measured voxel size; field of view 360 mm; 4.03-min scan time) we performed an intraindividual study on 19 patients with the 1.5-T sequence as the standard of reference. Two radiologists analyzed the examinations in consensus with regard to tissue contrast (visualization of zonal anatomy of the uterus and/or delineation of pathologic findings) rated on a three-point scale (3 is 3.0 T better; 2 is 3.0 T equal; 1 is 3.0 T worse than 1.5 T). In addition, the signal difference between muscle and bone marrow was measured as a marker for tissue contrast. The analysis of the image quality comprised the level of the artifacts (rated on a five-point scale: 1 is no artifacts; 5 is nondiagnostic study), the visual signal-to-noise ratio (rated on a three-point scale) and detail delineation. Only minor artifacts were observed at both 1.5 and 3.0 T; the difference was not statistically significant. The visual signal-to-noise ratio and the delineation of image details were rated equal for 1.5 and 3.0 T. With regard to image contrast, both qualitative analysis as well as quantitative analysis revealed comparable image contrast for the 1.5- and 3.0-T protocols. Pathological findings were seen equally well with both field strengths. Clinically diagnostic pelvic studies of high image quality can be obtained using a 3.0-T scanner with our modified examination protocol. To fully exploit the capability of the high-field technique, and to point out potential advantages, further intraindividual studies are needed, with the adjustment of other imaging parameters to the high-field environment.

[Serotonin syndrome--a case account]. / Serotoninski sindrom--prikaz slucaja.

Beside a large number of pharmaceuticals available on our market having an impact on serotonergic transmission, selective serotonin reuptake blocker inhibitors (fluvoxamine, fluoxetine) and a selective reversible monoaminooxidase inhibitor (moclobemide), have been included recently. The combination of the drugs can in certain conditions cause a central serotonergic hyperactivity, i.e. the serotonin syndrome. The study describes the development of the serotonin syndrome following an abrupt replacement of trazodone by moclobemide. The diagnosis was made on the basis of the anamnesis, clinical features, course and outcome of the disorder and diagnostic criteria suggested in the literature. The importance of the prevention, early detection and timely management of the serotonin syndrome have been reflected in the fact that some of the outcomes described were fatal, although this state most frequently remits spontaneously after the replacement of the drug therapy.

[Genetic factors in the onset of schizophrenia]. / Genetski faktori u nastanku shizofrenije.

The importance of inheritance in the development of schizophrenia was recorded in classic papers by Kraepelin and Bleuler. These observations have been confirmed by the contemporary research. In this paper, we summarize the results of genetic-epidemiological studies that include family, twin and adoption studies, as well as the results of segregation analysis and molecular-genetic research. Family studies indicate increased morbidity risk in the relatives of patients with schizophrenia, that augments with the degree of relation. Twin studies also suggest the importance of genetic factors demonstrating higher rates of concordance for the disorder in monozygotic (MZ) than in dizygotic (DZ) twins and consistent MZ/DZ ratios across the studies. Adoption studies provide further evidence for genetic vulnerability, showing an association between biological relatives separated at birth. The concept of "schizophrenia spectrum" is based on the observation of the familial aggregation of several hierarchically defined disorders in relatives of schizophrenic probands. Schizophrenia, schizoaffective disorder, schizotypal and paranoid personality disorder, other nonaffective psychoses and psychotic affective disease, according to this concept, represent manifestations of varying severity, of the same underlying vulnerability, which is transmitted within families. The results of segregation analyses support rather polygenic than monogenic inheritance, if schizophrenia is genetically homogeneous. However, the possibility of genetic heterogeneity augments the interest for searching for vulnerability genes with linkage. The results of linkage studies, indicating association between schizophrenia and markers on chromosomes 5, 6, 8 and 22, have not yet been replicated on independent samples of probands. Recent findings indicate that schizophrenia may be caused by unstable DNA (the expansion of trinucleotide repeated sequences at the disease locus). This could explain the departure from Mendelian inheritance, highly variable phenotype and wide ranging age of onset in schizophrenia. Further research in this field could not only clarify the mode of the transmission of the liability for schizophrenia and the relationship of genetic and environmental factors in the development of the disorder, but also determine which characteristics, behavior and physiological variables schizophrenia genes code for. This would, in addition, contribute to our understanding of the biological basis of schizophrenia.