Patient care and access to clinical trials in gynaecological oncology: global implications of the early phase of the COVID-19 pandemic.

PURPOSE: Our prospective international survey evaluated the impact of the early phase of the COVID-19 pandemic on the management gynaecological malignancies from the multidisciplinary physicians' perspective with particular focus on clinical infrastructures and trial participation. METHODS: Our survey consisted of 53 COVID-related questions. It was sent to healthcare professionals in gynaecological oncology centres across Europe and Pan-Arabian region via the study groups and gynaecological societies from April 2020 to October 2020. All healthcare professionals treating gynaecological cancers were able to participate in our survey. RESULTS: A total of 255 answers were collected from 30 countries. The majority (73%) of participants were gynaecological oncologists from university hospitals (71%) with at least an Intensive Care Unit with cardiopulmonary support available at their institutions. Most institutions continued to perform elective surgeries only for oncological cases (98%). Patients had to wait on average 2 weeks longer for their surgery appointments compared to previous years (range 0-12 weeks). Most cases that were prioritised for surgical intervention across all gynaecological tumours were early-stage disease (74%), primary situation (61%) and good ECOG status (63%). The radicality of surgery did not change in the majority of cases (78%) across all tumour types. During the pandemic, only 38% of clinicians stated they would start a new clinical trial. Almost half of the participants stated the pandemic negatively impacted the financial structure and support for clinical trials. Approximately 20% of clinicians did not feel well-informed regarding clinical algorithm for COVID-19 patients throughout the pandemic. Thirty percent stated that they are currently having trouble in providing adequate medical care due to staff shortage. CONCLUSION: Despite well-established guidelines, pandemic clearly affected clinical research and patientcare. Our survey underlines the necessity for building robust emergency algorithms tailored to gynaecological oncology to minimise negative impact in crises and to preserve access to clinical trials.

Evaluation of cleaved caspase-3 and Ki-67 index on diagnostic biopsy in response to neoadjuvant chemotherapy in the context of post-treatment tumour ypT stage, ypN stage, grade, and molecular subtype.

Introduction: Breast carcinoma is a heterogeneous disease, characterised by diverse clinical behaviour. The aim of this study was to assess how cleaved caspase-3 and Ki-67 index, evaluated on diagnostic biopsy, are related to response to neoadjuvant chemotherapy in the context of molecular subtype, post-treatment tumour, N category, and grade. Material and methods: A retrospective analysis was carried out among 110 breast cancer patients. Ki-67 levels and caspase-3 expression on diagnostic biopsy were explored regarding their relation to tumour grade and molecular subtype, ypT, ypN categories, and T and N categories according to Sataloff tumour response evaluation. Results: A statistically significant relationship was found between Ki-67 levels and tumour grade K-W = 24.2932, p < 0.0001; molecular subtype K-W = 28.5439, p < 0.00000967538; size and invasion of the primary tumour after neoadjuvant chemotherapy K-W = 11.7944, p < 0.0377169; caspase-3 expression after neoadjuvant therapy, evaluated according to the Sataloff classification χ2 = 5.97, df = 1, p = 0.0145. Discussion: No significant difference was found between Ki-67 expression in patients with pathological complete response, compared to those with partial and no response, a statistically significant difference in cases with different molecular subtype, histology grade, and tumour stage after neoadjuvant therapy. Cleaved caspase-3-positive breast cancer cases are often better responders to neoadjuvant therapy, but with no significant correlation to molecular subtype, high-grade categories, or tumour stage. Conclusions: The caspase-3 and Ki-67 index on diagnostic biopsy are related to post-neoadjuvant treatment prognostic factors (ypT stage, grade), proving them useful for prediction of treatment response to neoadjuvant therapy and further patient management.

Role of Creative Therapies in Gynecological Oncology: Results of a Multigenerational Survey in Patients and Caregivers.

INTRODUCTION: Although creative therapies like painting, dancing, and writing are often used and encouraged to treat various diseases, including cancer, there are few systematic scientific studies on innovative therapies in medical care. METHODS: An anonymous survey was developed for female patients, their relatives, and female medical staff on the impact of creative therapies on optimizing clinical therapy management in exclusively female trials. RESULTS: Of 718 respondents, 358 were female patients, 69 were medical personnel, and 291 were in the control group. Overall, 91.2% of respondents had sought access to creative therapies, indicating strong self-motivated engagement in activities to improve health and well-being. This study also uncovered a significant preference for creative writing among patients. Furthermore, the data suggest that integrating innovative therapies into biopsychosocial anamnesis could offer valuable insights into patients' mobility, mood, and social behaviors. Despite a general hesitation to discuss leisure activities with medical professionals, many patients wanted to incorporate creative activities into their treatment plans. Moreover, group settings for innovative therapy were preferred, highlighting the need for more structured support in medical environments to facilitate these therapeutic interactions. CONCLUSIONS: This study suggests creative therapies can be valuable in medical care.

How to break bad news and how to learn this skill: results from an international North-Eastern German Society for Gynecological Oncology (NOGGO) survey among physicians and medical students with 1089 participants

BACKGROUND: Delivering bad news to patients is one of the most challenging tasks in medical practice. Despite its great relevance to patients, relatives, and medical staff, there is a paucity of data pertaining to training, experience, expectations, and preferences of physicians and medical students on breaking bad news. METHODS: We conducted an international survey in Germany, Switzerland, and Austria using an online questionnaire among physicians and medical students. RESULTS: A total of 786 physicians and 303 medical students completed the survey. Physicians stated that 32.7% deliver bad news several times a week and 45.2% several times a month. Difficulties controlling their emotions (35.1%) and remaining professional (43.4%) were the greatest challenges for physicians. Delivering bad news is associated with feelings of anxiety, both among experienced physicians (median of 3.8 out of 10.0) and medical students (median of 5.3). Conveying bad news is a burden to physicians and consequently has a substantial impact on their job satisfaction. All participants reported the need for more communication training concerning this subject. Only 49.5% of medical students and 67.3% of physicians mentioned having learned adequate communication skills. Our data demonstrate that communication training decreases the level of anxiety and increases the feeling of self-confidence towards breaking bad news. Preferred educational tools were seminars with simulation (students: 71.4%, physicians: 49.5%), observing more senior faculty (students: 57.4%, physicians: 55.1%), and supervision and feedback sessions (students: 36.3%, physicians: 45.7%). The largest barriers regarding education on communication were limited time (students: 77.0%, physicians: 74.9%) and missing awareness of supervisors (students: 60.6%, physicians: 41.1%). CONCLUSIONS: Our study showed a great need for systematic training and education in breaking bad news among physicians and medical students. Hospitals, medical schools, and postgraduate training programs are strongly encouraged to fill this gap, and improve sustainable doctor-patient communication to overcome the psychological burden for physicians.

[Promoting intercultural competencies in the healthcare sector through further education and training]. / Interkulturelle Kompetenzen im Gesundheitswesen durch Fort- und Weiterbildungen fördern.

Acceptance of cultural diversity and the recognition and appreciation of facets of "otherness" such as gender, age, occupational or disease-related group, religion, sociocultural background, and migration history are basic requirements for adequate communication and interaction in healthcare. The term intercultural competence is multidimensional and includes a range of qualities and skills with emotional and cognitive elements with influence on the behavioral level. In the present paper, we discuss the importance of intercultural competence for the healthcare system and which aspects of the intercultural communication are particularly relevant for culturally sensitive medical care. Additionally, we report on the implementation of an interprofessional program and continuing education concept for clinical practice: Interprofessional and Intercultural Work in Medicine, Nursing and Social Services (IPIKA).The basis of the specific approaches to improving intercultural competence should be the systematic education and training of basic communication skills. This concerns almost all curricula for the medical professions. It is important to emphasize that intercultural competence is a core and cross-sectional topic for all healthcare providers.

Initial experience in target peroral endoscopic submucosal myotomy combined with septotomy for epiphrenic diverticulum.

The epiphrenic esophageal diverticulum is a rare non-malignant condition that is commonly associated with motility disorders. It would normally be treated surgically, but with the advancement of endoscopy techniques, peroral endoscopic myotomy with septotomy (D-POEM) has shown its benefits in coping with the symptoms. We present a case of a 71-year-old woman with increasing symptoms of dysphagia, weight loss and imaging data showing a large epiphrenic diverticulum. We treated her using peroral endoscopic myotomy combined with septotomy of the diverticular septum. The procedure showed excellent results with reducing the amount of contrast materials retained in it, improving the quality of life of the patient, and increasing her weight. There were minimal adverse events and no perforations or severe adverse effects occurred. D-POEM is a new and rapidly evolving procedure that is proving to be a safe and effective method of treating epiphrenic esophageal diverticulum.

Knowledge and understanding risk factors and preventive measures for osteoporosis in women: results of a survey in 502 women with and without a migration background.

BACKGROUND: Osteoporosis is a disease of the skeletal system associated with loss of bone mass and an increased risk of fractures affecting women more often than men. Identification of the knowledge about osteoporosis and its preventive methods is the backbone of any awareness program. This study investigates the knowledge with a special focus on women with and without a migration background. METHODS: Data from systematic patient interviews based on a questionnaire were collected at three different sites in Berlin between February and June 2021. The survey included questions assessing migrant background, demographic characteristics, lifestyle habits including physical exercise and smoking, prevention by vitamin D intake and bone densitometry, and information on personal and family medical history. According to the responses, a scale was created to assess the level of knowledge of preventive osteoporosis measures. The ethic committee of the Charité, Medical faculty has approved this study. SPSS (version 24.0) was used for the statistical analyses. RESULTS: The survey of 502 female patients revealed that 25% had low and 34% no previous knowledge of osteoporosis. Older age and a better education level correlate with a higher knowledge. Patients with gynecologic cancer are less well informed. There is a significant difference in vitamin D intake between migrant and non-migrant women (57% vs. 49%). There were no significant differences regarding the use of bone densitometry. CONCLUSION: Knowledge of osteoporosis and the possibility of a bone densitometry as well as the implementation of preventive measures is low among women. Therefore, informing patients better should be a priority, with particular attention on the risks and needs of women with a migration background. Specific programs for women with and without migration background should be developed to increase the awareness of osteoporosis.

Rates of severe complications in patients undergoing colorectal surgery for deep endometriosis-a retrospective multicenter observational study.

INTRODUCTION: Surgical experience and hospital procedure volumes have been associated with the risk of severe complications in expert centers for endometriosis in France. However, little is known about other certified units in Central European countries. MATERIAL AND METHODS: This retrospective observational study included 937 women who underwent surgery for colorectal endometriosis between January 2018 and January 2020 in 19 participating expert centers for endometriosis. All women underwent complete excision of colorectal endometriosis by rectal shaving, discoid or segmental resection. Postoperative severe complications were defined as grades III-IV of the Clavien-Dindo classification system including anastomotic leakage, fistula, pelvic abscess and hematoma. Surgical outcomes of centers performing less than 40 (group 1), 40-59 (group 2) and ≥60 procedures (group 3) over a period of 2 years were compared. RESULTS: The overall complication rate of grade III and IV complications was 5.1% (48/937), with rates of anastomotic leakage, fistula formation, abscess and hemorrhage in segmental resection, discoid resection and rectal shaving, respectively, as follows: anastomotic leakage 3.6% (14/387), 1.4% (3/222), 0.6% (2/328); fistula formation 1.6% (6/387), 0.5% (1/222), 0.9%; (3/328); abscess 0.5% (2/387), 0% (0/222) and 0.6% (2/328); hemorrhage 2.1% (8/387), 0.9% (2/222) and 1.5% (5/328). Higher overall complication rates were observed for segmental resection (30/387, 7.8%) than for discoid (6/222, 2.7%, P = 0.015) or shaving procedures (12/328, 3.7%, P = 0.089). No significant correlation was observed between the number of procedures performed and overall complication rates (rSpearman  = -0.115; P = 0.639) with a high variability of complications in low-volume centers (group 1). However, an intergroup comparison revealed a significantly lower overall severe complication rate in group 3 than in group 2 (2.9% vs 6.9%; P = 0.017) without significant differences between other groups. CONCLUSIONS: A high variability in complication rates does exist in centers with a low volume of activity. Major complications may decrease with an increase in the volume of activity but this effect cannot be generally applied to all institutions and settings.

URANIUM AND 210PO RADIONUCLIDES IN DRINKING WATER IN SOUTHERN BULGARIA AND EXPECTED RADIATION DOSES.

The activity concentrations of the naturally occurring radionuclides 238U, 234U and 210Po have been determined for the first time in drinking water from certain sources in Southern Bulgaria using nuclear and radiochemical methods. The results obtained for the water samples vary in the intervals 0.6-678 mBq l-1 for 238U, 1.4-1484 mBq l-1 for 234U, <0.3-13.6 mBq l-1 for 210Po and 1.04-10.6 for the 234U/238U ratio. The annual effective dose from 238U, 234U and 210Po ranges from 1.09 to 44.1 µSv y-1, 0.78 to 46.8 µSv y-1 and 0.77 to 62.8 µSv y-1 for infants, children and adults, respectively. The annual effective dose due to consumption of drinking water is below the individual dose criterion of 100 µSv y-1 recommended by the World Health Organization. The natural radioactivity of the water sources investigated is below the national and international limits.

Patients' subjective assessment as a decisive predictor of malignancy in pelvic masses: results of a multicentric, prospective pelvic mass study.

OBJECTIVE: The prognosis for ovarian cancer patients remains poor. A key to maximizing survival rates is early detection and treatment. This requires an accurate prediction of malignancy. Our study seeks to improve the accuracy of prediction by focusing on early subjective assessment of malignancy. We therefore investigated the assessment of patients themselves in comparison to the assessment of physicians. METHODS: One thousand three hundred and thirty patients participated in a prospective and multicenter study in six hospitals in Berlin. Using univariate analysis and multivariate logistic regression models, we measured the accuracy of the early subjective assessment in comparison to the final histological outcome. Moreover, we investigated factors related to the assessment of patients and physicians. RESULTS: The patients' assessment of malignancy is remarkably accurate. With a positive predictive value of 58%, the majority of patients correctly assessed a pelvic mass as malignant. With more information available, physicians achieved only a slightly more accurate prediction of 63%. CONCLUSIONS: For the first time, our study considered subjective factors in the diagnostic process of pelvic masses. This paper demonstrates that the patients' personal assessment should be taken seriously as it can provide a significant contribution to earlier diagnosis and thus improved therapy and overall prognosis.

Online survey on uterotomy closure techniques in caesarean section.

OBJECTIVES: Uterine closure technique in caesarean section (CS) influences the rate of late complications in subsequent pregnancies. As no common recommendation on suture techniques exists, we developed a questionnaire to determine the techniques currently used and the frequencies of late complications. METHODS: The online questionnaire consisted of 13 questions and was sent to 648 obstetric hospitals (level I-IV) in Germany. Number of CS, rate of vaginal birth after caesarean section (VBAC), the type of uterus suturing technique and the frequency of uterine dehiscences, ruptures and placenta accreta spectrum (PAS) were queried. The answers were anonymous, and results were evaluated descriptively. RESULTS: The response rate was 24.7%. The mean CS rate was 27.3% (±6.2), the repeat CS rate 33.2% (±18.1). After CS, 46.2% (±20.2) women delivered vaginally. To close the uterotomy, 74.4% of hospitals used single layer continuous sutures, 16.3% single layer locked sutures, 3.8% interrupted sutures, 3.1% double layer continuous sutures and 2.5% used other suture techniques. The percentages of observed uterine dehiscences did not differ significantly between the different levels of care nor did the uterotomy suture techniques. CONCLUSIONS: There is no uniform suturing technique in Germany. A detailed description of suture technique in surgery reports is required to evaluate complications in subsequent pregnancies. National online surveys on obstetric topics are feasible and facilitate the discussion on the need to define a standardized uterine closure technique for CS.

Preoperative CA-125 Value as a Predictive Factor for Postoperative Outcome in First Relapse of Platinum-sensitive Serous Ovarian Cancer.

AIM: The purpose of the study was to evaluate whether preoperative cancer antigen 125 (CA-125) levels predict outcome of secondary cytoreductive surgery (SCS) in patients with serous recurrent ovarian cancer and whether this could be used as a prognostic factor for progression-free (PFS) and overall (OS) survival. PATIENTS AND METHODS: A cohort of 111 patients with first recurrence of platinum-sensitive serous ovarian cancer, who had undergone SCS at the Department of Gynecology and Oncological Surgery, Charité, Campus Virchow Clinic was analyzed in correlation with the preoperative CA-125 value. RESULTS: The median preoperative CA-125 level was 164 U/ml. Complete tumor resection was achieved in 58.6% of the patients. PFS and OS for patients with preoperative CA-125 of less than 164.5 U/ml was significantly better than those with preoperative CA-125 ≥164.5 U/ml (p=0.025 and p<0.001, respectively). CONCLUSION: Preoperative CA-125 is not a statistically significant predictive factor for complete tumor resection after SCS. Preoperative CA-125 <164.5 U/ml can predict significantly better PFS and OS for patients with first recurrence of platinum-sensitive ovarian cancer.

Genetic Versus Epigenetic BRCA1 Silencing Pathways: Clinical Effects in Primary Ovarian Cancer Patients: A Study of the Tumor Bank Ovarian Cancer Consortium.

OBJECTIVES: The aim of the present study was to assess in a large cohort of primary epithelial ovarian cancer patients the incidence and the clinical effect of BRCA1 genetic and epigenetic silencing mechanisms. METHODS: A total of 188 primary epithelial ovarian cancer patients, treated between 2000 and 2011 at the Charité University Hospital of Berlin, were included. The patients' tumor and blood samples were obtained from the Tumor Bank Ovarian Cancer Network (www.toc-network.de). Direct sequencing of BRCA1 exon 11 was performed to detect germline mutations, whereas tumor samples were assessed for BRCA1 promoter hypermethylation by bisulphite-converted methylation-specific polymerase chain reaction. Basing on their BRCA1 status, patients were compared regarding clinicopathological variables and survival. RESULTS: Twenty-one patients (11.2%) showed hypermethylation in BRCA1 promoter (HMB), and 18 patients (9.6%) presented germline mutations in BRCA1 exon 11 (GMB). Patients with HMB showed a significantly younger age at diagnosis compared with BRCA1 wild type (BWT) patients (54 vs 61 years, P = 0.045), and both GMB and HMB patients were more likely to have high-grade serous ovarian cancer (76.2% and 77.8% vs 52.7%, P = 0.043 and P = 0.043). Positive family history of breast or ovarian cancer (OC) was more frequently reported among GMB patients with respect to BWT patients (44.4% vs 13.5%, P = 0.003); GMB, HMB, and BWT patients did not show significant differences in terms of tumor dissemination pattern, surgical outcomes, platinum response or survival; neither mutational nor hypermethylation BRCA1 status was found to be an independent prognostic factor for OC patients. CONCLUSIONS: Hypermethylation in BRCA1 is associated with earlier occurrence of OC. In addition, the coexistence of both GBM and HMB is an infrequent event, occurring in 0.5% of OC cases. Silencing of BRCA1 through mutation and hypermethylation confers to distinct clinical characteristics of OC patients but similar clinical outcome with respect to BWT patients.

A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO).

OBJECTIVE: In recurrent ovarian cancer (ROC), there is a high demand on effective therapies with a mild toxicity profile. Treosulfan is an alkylating agent approved as oral (p.o.) and intravenous (i.v.) formulation for the treatment of recurrent ovarian cancer. Data on safety and efficacy for either formulation are rare. For the first time we conducted a randomized phase III study comparing both formulations in women with ROC. METHODS: Patients having received at least two previous lines of chemotherapy were randomly assigned to one of two treatment arms: treosulfan i.v. 7000 mg/m2 d1 q4w or treosulfan p.o. 600 mg/m2 d1-28 q8w. Primary endpoint was safety regarding hematological and gastrointestinal toxicity grade III/IV, secondary endpoints were other toxicities, clinical benefit rate (CBR), time to progression (TTP), overall survival (OS) and quality of life. RESULTS: 250 patients were treated with treosulfan i.v. (128) or treosulfan p.o. (122). In general treosulfan therapy was well tolerated in both treatment arms. Leukopenia grade III/IV occurred significantly more frequently in the p.o. arm (3.9% i.v. arm, 14.8% p.o. arm, p = 0.002). Other toxicities were similar in both arms. CBR was comparable between arms (41.4% i.v. arm, 36.9% p.o. arm). No difference in TTP (3.7 months i.v. arm, 3.5 months p.o. arm) or OS (13.6 months i.v. arm, 10.4 months p.o. arm, p = 0.087) occurred. CONCLUSIONS: Given the safety and efficacy results treosulfan is an acceptable option for heavily pretreated OC patients. Regarding the toxicity profile the i.v. application was better tolerated with less grade III and IV toxicities.

Implementation of Enhanced Recovery After Surgery (ERAS) Pathways in Gynecologic Oncology. A NOGGO-AGO* survey of 144 Gynecological Departments in Germany.

AIM: To gather standardized information of current perioperative management of gynecological oncology patients and to evaluate up to what extent the Enhanced Recovery after Surgery (ERAS) elements are established in the clinical routine of gynecologic oncology units in Germany. MATERIALS AND METHODS: We performed a multi-centric nationwide survey among 654 primary, secondary and maximal health care gynecological departments in Germany. A multiple-choice questionnaire based on the principles of ERAS was developed to gather information about perioperative management of two fictional cases in gynecological oncology. RESULTS: One hundred four units (22%) have been taken the survey. Only 49.5% of surveyed hospitals claimed to be adherent to more than 70% of ERAS elements in managing perioperative period of primary cytoreductive surgery in ovarian cancer patients. 21% of these hospitals implemented more than 80% and only 8.4% implemented more than 90%. The results in border-line tumors operations did not differ from those of ovarian cancer operations. CONCLUSION: The implementation of ERAS elements in gynecologic oncology in Germany is still not satisfying as only half of the departments will now be able to apply 70% of these principles. Therefore, we plan the second step of this survey in order to be able to build a consistent structured reporting platform between gynecological oncology units in Germany to facilitate the wide implementation and standardization of ERAS protocol.

Germline mutations of BRCA1 gene exon 11 are not associated with platinum response neither with survival advantage in patients with primary ovarian cancer: understanding the clinical importance of one of the biggest human exons. A study of the Tumor Bank Ovarian Cancer (TOC) Consortium.

Germline mutations in BRCA1 gene have been reported in up to 20 % of epithelial ovarian cancer (EOC) patients. Distinct clinical characteristics have been attributed to this special EOC population. We hypothesized that mutations in different BRCA1 gene exons may differently affect the clinical course of the disease. The aim of this study was to analyze, in a large cohort of primary EOCs, the clinical impact of mutations in BRCA1 gene exon 11, the largest exon of the gene sequence encoding the 60 % of BRCA1 protein. Two hundred sixty-three primary EOC patients, treated between 2000 and 2008 at Charité University Hospital of Berlin, were included. Patients' blood samples were obtained from the Tumor Ovarian Cancer (TOC) Network ( www.toc-network.de ). Direct sequencing of BRCA1 gene exon 11 was performed for each patient to detect mutations. Based on their BRCA1 exon 11 mutational status, patients were compared regarding clinico-pathological variables and survival. Mutations in BRCA1 exon 11 were found in 18 out of 263 patients (6.8 %). Further 10/263 (3.8 %) cases showed variants of uncertain significance (VUS). All exon 11 BRCA1-positive tumors (100 %) were Type 2 ovarian carcinomas (p = 0.05). Age at diagnosis was significantly younger in Type 2 exon 11 mutated patients (p = 0.01). On multivariate analysis, BRCA1 exon 11 mutational status was not found to be an independent predictive factor for optimal cytoreduction, platinum response, or survival. Mutations in BRCA1 gene exon 11 seem to predispose women to exclusively develop a Type 2 ovarian cancer at younger age. Exon 11 BRCA1-mutated EOC patients showed distinct clinico-pathological features but similar clinical outcome with respect to sporadic EOC patients.

Expression of epithelial cell adhesion molecule in paired tumor samples of patients with primary and recurrent serous ovarian cancer.

OBJECTIVE: Ovarian cancer (OC) recurrence constitutes a therapeutic dilemma with various novel targeted agents emerging that offer alternative treatment options. The aim of the present study was to evaluate and compare epithelial cell adhesion molecule (EpCAM) expression profiles in paired tumor samples of patients with OC relapse. METHODS: EpCAM expression was analyzed by immunohistochemistry using the avidin-biotin-complex method on paraffin-embedded OC tissues obtained at primary surgery as well as on corresponding tumor samples of the same patients at relapse. The EpCAM overexpression was defined as 76% to 100% of tumor cells positively stained for EpCAM. Clinical data were collected within the Tumorbank Ovarian Cancer Network. RESULTS: Nineteen patients with serous OC histology were included in the study (median age at primary diagnosis, 50 years; range, 40-74 years). The majority of the patients (95%) presented with International Federation of Gynecology and Obstetrics stage III/IV, and 68.4% of the tumors were poorly differentiated. A complete macroscopic tumor resection could be achieved in 15 patients (78.9%) at diagnosis. Epithelial cell adhesion molecule overexpression was detected in 17 (89%) of the primary and 16 (84%) of the recurrent tumors (P = 1.0); hence, no significant change of the EpCAM expression profile could be identified over time. CONCLUSIONS: Epithelial cell adhesion molecule expression profile appears to remain stable during the course from the primary throughout the relapse of serous OC. The results indicate that EpCAM might be an interesting therapeutic target structure in serous OC.

High Archaea diversity in Varvara hot spring, Bulgaria.

The phylogeny of the latest recognized domain, Archaea, is still complicated and it is largely based on environmental sequences. A culture independent molecular phylogenetic analysis revealed high Archaea diversity in a terrestrial hot spring, village Varvara, Bulgaria. A total of 35 archaeal operational taxonomic units (OTUs) belonging to three of the classified five Archaea phyla were identified. Most of the sequences were affiliated with the phylum Crenarchaeota (23), grouped in four branches. The rest of the sequences showed highest similarity to the unidentified archaeal clones (9), Euryarchaeota (2), and "Korarchaeota " (1). Eight (23%) of the sequenced 16S rDNAs didn't have known close relatives and represented new and diverse OTUs, four of them forming a new archaeal subgroup without close described sequences or culturable relatives. A sequence affiliated with "Korarchaeota " showed low similarity (90%) to the closest neighbor and both sequences formed unique branch in this phylum. Consequently, the constructed archaeal libraries are characterized by (1) high proportion of OTUs representing uncultivated archaeal phylogroups, (2) the abundance of novel phylotype sequences, (3) the presence of high proportions of Crenarchaeota phylotypes unrelated to cultivated organisms and (4) the presence of a sequence only distantly related to "Korarchaeota " phylum.