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Infektionen sind eine wichtige potenzielle Gefahrenquelle für Schwangere und ihre ungeborenen Kinder. Schwangere und Frauen mit Kinderwunsch sollten sich daher fachkundig darüber beraten lassen, welche Impfungen vor bzw. während einer Schwangerschaft sinnvoll sind. Zur Impfberatung gehören auch Fragestellungen zu Reiseimpfungen, insbesondere wenn das Reiseziel in einem Endemiegebiet für Erkrankungen wie Malaria, Gelbfieber, Tuberkulose, Hepatitis, Human-immunodeficiency-virus-assoziierte Erkrankungen, Leishmaniose, Toxoplasmose und Japanische Enzephalitis liegt. Grundsätzlich können alle Toxoidimpfstoffe, inaktivierten Impfstoffe und Immunglobuline in der Schwangerschaft verabreicht werden, Lebendimpfstoffe sind kontraindiziert. Empfehlenswerte Impfungen in der Schwangerschaft sind Tetanus, Diphtherie, Pertussis im Falle eines fehlenden Impfschutzes, die saisonale Influenzaimpfung und aktuell die Coronavirus-disease-19(COVID-19)-Impfung ab dem zweiten Trimenon. Zu den empfohlenen Reiseschutzimpfungen zählen alle Standardimpfungen, das heißt die Grundimmunisierung gegen Rotaviren, Tetanus, Diphtherie, Pertussis, Haemophilus influenzae Typ B, Poliomyelitis, Hepatitis B, Pneumokokken, Meningokokken, Masern, Mumps, Röteln, Varizellen, humanes Papillomavirus und Influenza. Darüber hinaus hat in der Reisemedizin der Immunschutz gegen Hepatitis A einen hohen Stellenwert. Nach den internationalen Gesundheitsempfehlungen der World Health Organization ist zur Einreise in bzw. Ausreise aus bestimmten Ländern eine zusätzliche spezifische Impfvorschrift für die Gelbfieber- und Poliomyelitisimpfung vorgesehen. Einzelne Länder haben darüber hinaus zusätzliche Impfvorschriften für die Ein- und Ausreise. „Indikationsimpfungen“ setzen ein entsprechendes lokales Risiko voraus.

P1 oncogenerative cell division as a whole cell entity is shown here.

The effects of anticancer treatments on cell heterogeneity and their proliferative potential play an important role in tumor persistence and metastasis. However, little is known about de-polyploidization, cell fate, and physiologic stemness of the resulting cell populations. Here, we describe a distinctive cell type termed "pregnant" P1 cells found within chemotherapy-refractory ovarian tumors, which generate and gestate daughter generation Gn cells intracytoplasmically. Release of Gn cells occurred by ejection through crevices in the P1 cell membrane by body contractions or using a funiculus-like structure. These events characterized a not yet described mechanism of cell segregation. Maternal P1 cells were principally capable of surviving parturition events and continued to breed and nurture Gn progenies. In addition, P1 cells were competent to horizontally transmit offspring Gn cells into other specific proximal cells, injecting them to receptor R1 cells via cell–cell tunneling. This process represents a new mechanism used by tumor cells to invade surrounding tissues and ensure life cycles. In contrast to the pregnant P1 cells with low expression of stem cell markers despite their physiologic stemness, the first offspring generations of daughter G1 cells expressed high levels of ovarian cancer stem cell markers. Furthermore, both P1 and Gn cells overexpressed multiple human endogenous retroviral envelope proteins. Moreover, programmed death-ligand 1 and the immunosuppressive domain of the retroviral envelope proteins were also overexpressed in P1 cells, suggesting effective protection against the host immune system. Together, our data suggest that P1 oncogenerative cancer cells exhibit a not yet described cell biological mechanism of persistence and transmission of malignant cells in patients with advanced cancers.Significance: P1 oncogenerative cell entities express low levels of CSC markers, which are characteristic of their histological origin. Cancer Res; 78(9); 2318–31. ©2018 AACR.

P1 cells seem to undergo divisions in to similar oncogenerative cells by cytoplasm separation. The process is in par orchestrated with the participation of mitochondria which delimitate boundaries of cytoplasms to be separated. After this, it is possible to observe a directional cytokinesis like separation of multinucleated cells.

Expression of CSC markers and morphology of P1 oncogenerative and G1-Gn cells as detected by ICC and IHC.

P1 reconstruction in 3D horizontal projection from TEM sections superposed. The inner structure of G1-containing cells is shown.

Replicative elements found in P1 and G1 cells and the expression of HERV envelope proteins in small G1-G2 cells can be visualised here.

P1 oncogenerative cells undergo long quiescent phases in which they do not appear to generate and eject G1 cells.

Resistance profile and spherogenicity of SKOV3 ovarian carcinoma models.

Oncogenerative P1 cells are giant cells with a syncytium-like morphology. This distinctive cell type complete cell life cycles which resemble lysogenic viral cycles. The mode of cellularization of the intracytoplasmically generated G1 cells (generation 1) is unique and takes place in different ways: a) in a lateral form which means that the G1 cells abandon the maternal P1 cells by trans cytoplasmic budding, b) through crevices formed with the participation of mitochondria around G1s until expulsion. After cellularization, the resulted aperture is filled by fusogenic HERV proteins, c) using a kind of funiculus or bridge connected to P1 maternal cells. An interesting process conducted by P1 cells is the horizontal transmission of G1 inoculating these cells into proximal receptor cells.

The lateral separation of G1 from P1 cells is observed in this clip.

The formation of the crevices is observed with the subsequent detachment of G1-Gn cells from mother cytoplasm.

P1 reconstruction in 3D vertical projection from TEM sections superposed. The inner structure of G1-containing cells is shown.

Occurrence and morphology of multinucleated cells in different tumors.

Oncogenerative P1 cells are giant cells with a syncytium-like morphology. This distinctive cell type complete cell life cycles which resemble lysogenic viral cycles. The mode of cellularization of the intracytoplasmically generated G1 cells (generation 1) is unique and takes place in different ways: a) in a lateral form which means that the G1 cells abandon the maternal P1 cells by trans cytoplasmic budding, b) through crevices formed with the participation of mitochondria around G1s until expulsion. After cellularization, the resulted aperture is filled by fusogenic HERV proteins, c) using a kind of funiculus or bridge connected to P1 maternal cells. An interesting process conducted by P1 cells is the horizontal transmission of G1 inoculating these cells into proximal receptor cells.

Expression of CSC markers in multinucleated cells at protein and RNA levels.

Purpose The aim was to develop and update a guideline which would improve the quality of care offered to women with gestational and non-gestational trophoblastic disease, a group of diseases characterized by their rarity and biological heterogeneity. Methods In accordance with the method used to compile S2k-guidelines, the guideline authors carried out a search of the literature (MEDLINE) for the period 1/2020 to 12/2021 and evaluated the recent literature. No key questions were formulated. No structured literature search with methodical evaluation and assessment of the level of evidence was carried out. The text of the precursor version of the guideline from 2019 was updated based on the most recent literature, and new statements and recommendations were drafted. Recommendations The updated guideline contains recommendations for the diagnosis and therapy of women with hydatidiform mole (partial and complete moles), gestational trophoblastic neoplasia after pregnancy or without prior pregnancy, persistent trophoblastic disease after molar pregnancy, invasive moles, choriocarcinoma, placental site nodules, placental site trophoblastic tumor, hyperplasia at the implantation site und epithelioid trophoblastic tumor. Separate chapters cover the determination and assessment of human chorionic gonadotropin (hCG), histopathological evaluation of specimens, and the appropriate molecular pathological and immunohistochemical diagnostic procedures. Separate chapters on immunotherapy, surgical therapy, multiple pregnancies with simultaneous trophoblastic disease, and pregnancy after trophoblastic disease were formulated, and the corresponding recommendations agreed upon.

Cervical dysplasia is a common precancerous lesion affecting 1% to 2% of women worldwide. Significant progress in the diagnosis and treatment of cervical dysplasia have been made in the last decade. We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify controlled clinical trials reporting on the efficacy and safety of diagnostic and therapeutic interventions for cervical dysplasia. Data were analyzed according to PRISMA guidelines. In total, 33 studies reporting on 5935 women were identified. We recommend intravenous or intracervical lidocaine for pain reduction during colposcopically-directed cervical biopsies but not topical lidocaine, music, or video colposcopy. Monsel’s solution might be used to control bleeding after cervical biopsies. The acetic acid test should be scored 1 min after the application of acetic acid and should be followed by Lugol’s iodine test for an optimal yield of LSIL/HSIL. LEEP/LLETZ remains the standard and techniques such as SWETZ, C-LETZ, and TCBEE are not superior. LEEP/LLETZ should be performed under local anesthesia and with direct colposcopic vision. Cryotherapy and thermoablation might be used in women with LSIL, especially in women with HIV infection, but LEEP/LLETZ remains the standard for HSIL. Topical imiquimod remains an experimental procedure. In conclusion, significant progress has been made in the last decade regarding both diagnostic interventions as well as therapeutic interventions for women with cervical dysplasia. Based on >30 controlled clinical trials, we were able to formulate specific and evidence-based recommendations.

Objectives Safe implementation and thorough evaluation of new treatments require prospective data monitoring and standardization of treatments. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising alternative for the treatment of patients with peritoneal disease with an increasing number of suggested drug regimens. The aim was to reach expert consensus on current PIPAC treatment protocols and to define the most important research topics. Methods The expert panel included the most active PIPAC centers, organizers of PIPAC courses and principal investigators of prospective studies on PIPAC. A comprehensive literature review served as base for a two-day hybrid consensus meeting which was accompanied by a modified three-round Delphi process. Consensus bar was set at 70% for combined (strong and weak) positive or negative votes according to GRADE. Research questions were prioritized from 0 to 10 (highest importance). Results Twenty-two out of 26 invited experts completed the entire consensus process. Consensus was reached for 10/10 final questions. The combination of doxorubicin (2.1 mg/m2) and cisplatin (10.5 mg/m2) was endorsed by 20/22 experts (90.9%). 16/22 (72.7%) supported oxaliplatin at 120 with potential reduction to 90 mg/m2 (frail patients), and 77.2% suggested PIPAC-Ox in combination with 5-FU. Mitomycin-C and Nab-paclitaxel were favoured as alternative regimens. The most important research questions concerned PIPAC conditions (n=3), standard (n=4) and alternative regimens (n=5) and efficacy of PIPAC treatment (n=2); 8/14 were given a priority of ≥8/10. Conclusions The current consensus should help to limit heterogeneity of treatment protocols but underlines the utmost importance of further research.