Workforce planning and training in Obstetrics and Gynaecology across Europe: A survey of national trainee societies.

OBJECTIVE(S): To describe the infrastructural differences in training in Obstetrics and Gynaecology (ObGyn) across Europe. STUDY DESIGN: Descriptive web-based survey of 31 national ObGyn trainee societies representing the 30 member countries of the European Network of Trainees in Obstetrics and Gynaecology. Answers were verified in a telephone interview and only countries which had completed the telephone interview were included in the final analysis. RESULTS: The final analysis included 28 of 31 societies representing 27 countries (response rate 90%). The median formal duration of training was 5 years (range 4-7). There were mandatory requirements in addition to medical school graduation before specialisation could be started in 20 (71%) countries. The job opportunities after completion of training varied and included academic fellowships (n=21 [75%]), clinical fellowships/junior consultancy (n=21 [75%]), consultancy (n=11 [40%]), and private practice (n=23 [82%)]. Training and working as a specialist abroad was uncommon (≤20% in 21 [78%] and 26 [96%] countries respectively). Exams during ObGyn training were offered in 24 (85%) countries. Unemployment after completion of training was rare (<5% in 26 [93%] countries). Assessment of ObGyn specialists took place in 20 (71%) countries. CONCLUSION(S): The study illustrates that there are organisational variations in ObGyn training in Europe; A) The requirements to obtain a training post vary causing differences in the qualifications of trainees starting training. B) The duration of training varies. And C) newly trained specialists carry varying levels of responsibility. The results suggest that the content, organisation, and outcome of training differ across Europe. Differences due to political, social and cultural reasons are expected. However, further harmonisation of training across Europe still seems desirable in order to improve women's healthcare and facilitate the mobility of ObGyn trainees and specialists across Europe. There are currently several European initiatives, however, national and local measures are essential for training to improve.

Spectroimmunohistochemistry: a novel form of MALDI mass spectrometry imaging coupled to immunohistochemistry for tracking antibodies.

MALDI mass spectrometry imaging (MALDI-MSI) is currently used for clinical applications, such as biomarker identification, particularly for the study of solid tumors. The ability to map specific compounds that have been determined to be biomarkers and therapeutic targets is relevant for the evaluation of the efficacy of targeted therapies. This article describes a new method called Spectro-ImmunoHistoChemistry (SIHC), which combines the use of specific antibodies against markers and mass spectrometric imaging in the MS/MS mode. SIHC is based on direct primary antibody-antigen recognition, trypsin digestion of the antibody overlaying the markers of interest in the tissue section, and MALDI-MSI of the tryptic peptides generated from the antibody. This approach has both clinical and pharmacological applications. First, it can be used as a cross-validation method to monitor the presence specifically of a marker in a tissue section. Second, SIHC could potentially be used as a novel technology for tracking specific antibodies after in vivo injection for anti-cancer treatments. Additionally, SIHC could enable novel clinical applications of MSI, such as monitoring the efficacy of cytotoxic antibody treatments.

Proteomic analyses of serous and endometrioid epithelial ovarian cancers - cases studies - molecular insights of a possible histological etiology of serous ovarian cancer.

PURPOSE: Epithelial ovarian carcinogenesis may occur de novo on the surface of ovarian mesothelial epithelial cells or from cells originating in other organs. Foreign Müllerian cell intrusion into the ovarian environment has been hypothesized to explain the latter scenario. In this study, MALDI MS profiling technology was used to provide molecular insights regarding these potentially different mechanisms. EXPERIMENTAL DESIGN: Using MALDI MS profiling, the molecular disease signatures were established in their anatomical context. MALDI MS profiling was used on serous and endometrioid cancer biopsies to investigate cases of epithelial ovarian cancer. We then applied bioinformatic methods and identification strategies on the LC-MS/MS analyses of extracts from digested formalin-fixed, paraffin-embedded tissues. Extracts from selected regions (i.e. serous ovarian adenocarcinoma, fallopian tube serous adenocarcinoma, endometrioid ovarian cancer, benign endometrium, and benign ovarian tissues) were performed, and peptide digests were subjected to LC-MS/MS analysis. RESULTS: Comparison of the proteins identified from benign endometrium or three ovarian cancer types (i.e. serous ovarian adenocarcinoma, endometrioid ovarian adenocarcinoma, and serous fallopian tube adenocarcinoma) provided new evidence of a possible correlation between the fallopian tubes and serous ovarian adenocarcinoma. Here, we propose a workflow consisting of the comparison of multiple tissues in their anatomical context in an individual patient. CONCLUSION AND CLINICAL RELEVANCE: The present study provides new insights into the molecular similarities between these two tissues and an assessment of highly specific markers for an individualized patient diagnosis and care.

The C-terminal fragment of the immunoproteasome PA28S (Reg alpha) as an early diagnosis and tumor-relapse biomarker: evidence from mass spectrometry profiling.

This study reports on the C-terminal fragment of the 11S proteasome activator complex (PA28 or Reg alpha), a novel ovarian-specific biomarker of early and late stages of ovarian cancer (OVC) relapse, in patient biopsies after chemotherapy. A total of 179 tissue samples were analyzed: 8 stage I, 55 stage III-IV, 10 relapsed serous carcinomas, 25 mucinous carcinomas and 12 borderline and 68 benign ovarian tissue samples. This fragment was detected by MALDI mass spectrometry profiling in conjunction with a novel extraction method using hexafluoroisopropanol (1,1,1,3,3,3-hexafluoro-2-propanol; HFIP) solvents for protein solubilization and by immunohistochemistry using a specific antibody directed against the C-terminal fragment of PA28. Due to its specific cellular localization, this fragment is a suitable candidate for early OVC diagnosis, patient prognosis and follow-up during therapy and discriminating borderline cancers. Statistical analyses performed for this marker at different OVC stages reflect a prevalence of 77.66 ± 8.77 % (with a correlation coefficient value p < 0.001 of 0.601 between OVC and benign tissue). This marker presents a prevalence of 88 % in the case of tumor relapse and is detected at 80.5 % in stage I and 81.25 % ± 1.06 in stage III-IV of OVC. The correlation value for the different OVC stages is p < 0.001 of 0.998. Taken together, this report constitutes the first evidence of a novel OVC-specific marker.

Fetal microchimerism: benevolence or malevolence for the mother?

For a long time, the conventional view was that the fetus and maternal vascular system are kept separate. In fact there is a two way traffic of cells through the placenta and the transplacental passage of cells is in fact the norm. The fetal cells can persist in a wide range of woman's tissues following a pregnancy or an abortion and she becomes a chimera. Fetal cells have been found in the maternal circulation and they were shown to persist for the entire life in humans, thus demonstrating long-term engraftment and survival capabilities. Microchimerism is a subject of much interest for a number of reasons. Studies of fetal microchimerism during pregnancy may offer explanations for complications of pregnancy, such as preeclampsia, as well as insights into the pathogenesis of autoimmune diseases which usually ameliorate during pregnancy. The impact of the persistence of allogenic cells of fetal origin and of the maternal immunological response to them on the mother's health is still not clear. On the beneficial side, it has been proposed that genetically disparate fetal microchimerism provides protection against some cancers, that fetal microchimerism can afford the mother new mechanisms of protection to some diseases, that fetal microchimerism can enlarge the immunological repertoire of the mother improving her defense against aggressor. Fetal cells are often present at sites of maternal injury and may have an active role in the repair of maternal tissues.