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Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is increasingly used to manage gastric cancer peritoneal metastasis (GCPM). This study analyzed a prospective database of GCPM patients treated with cisplatin and doxorubicin PIPAC (PIPAC-C/D). The outcome criteria were adverse events, pathologic response [peritoneal regression grading score (PRGS)], and overall survival (OS). The PIPAC-C/D procedure was scheduled for 144 patients with a median age of 57 years (range 22–88 years). Access to the abdominal cavity for the first PIPAC failed in 11 patients (7.7 %). A total of 296 procedures were performed for 131 patients. Of the 144 patients, 52 (36.1%) underwent one PIPAC, 32 (22.2%) underwent two PIPACs, 24 (16.7%) underwent three PIPACs, and 21 (14.6%) underwent four or more PIPACs. The overall morbidity/mortality was grade 1 for 22 patients (15.3%), grade 2 for 32 patients (22.2%), grade 3 for 7 patients (4.9%), grade 4 for no patients (0%), and grade 5 for 2 patients (1.4%). Of the 37 patients who had three or more PIPACs eligible for histopathologic response analysis, 27 (73%) had major or complete regression (PRGS 1/2). A median OS of 11 months (range 0–61 months) for the total study population and 16 months (range 2–61 months) for the patients with three or more PIPACs was observed. For 10 patients (7%) who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, the median OS was 15 months (minimum, 4 months; maximum, 27 months). Multivariate analysis showed three or more PIPACs to be an independent prognostic factor for improved OS (hazard ratio, 0.36; p

Die Autoren der S3-Leitlinie „Diagnostik, Therapie und Nachsorge der Patientinnen mit Endometriumkarzinom“ finden keinen Beleg fur eine krankheitsspezifische Uberlebensverlangerung durch die onkologische Nachsorge und empfehlen entsprechend zuruckhaltend bei asymptomatischen Patientinnen nur die gezielte Anamnese und die klinische Untersuchung. Im Falle des konkreten Rezidivverdachts sollen hingegen die histologische Sicherung und die prazise Ausbreitungsdiagnostik mittels Ultraschalls und Schnittbildgebung erfolgen, um eine gezielte Rezidivtherapie planen zu konnen. Im Fokus der Beratung stehen die postaktinischen Beschwerden nach der Radiotherapie (RT) des Endometriumkarzinoms (EC) mit Auswirkungen auf das Sexualleben der betroffenen Frauen. Moglicherweise konnen in Zukunft eine risikoadaptierte Nachsorge des EC und gezielte rehabilitative Interventionen („survivorship care“) Kosten sparen und den Wunschen der Patientinnen noch mehr entgegenkommen.

Clinical trials of novel therapeutics for Alzheimer’s Disease (AD) have consumed a large amount of time and resources with largely negative results. Repurposing drugs already approved by the Food and Drug Administration (FDA) for another indication is a more rapid and less expensive option. We present DRIAD (Drug Repurposing In AD), a machine learning framework that quantifies potential associations between the pathology of AD severity (the Braak stage) and molecular mechanisms as encoded in lists of gene names. DRIAD is applied to lists of genes arising from perturbations in differentiated human neural cell cultures by 80 FDA-approved and clinically tested drugs, producing a ranked list of possible repurposing candidates. Top-scoring drugs are inspected for common trends among their targets. We propose that the DRIAD method can be used to nominate drugs that, after additional validation and identification of relevant pharmacodynamic biomarker(s), could be readily evaluated in a clinical trial., Clinical trials of novel therapeutics for Alzheimer’s Disease (AD) have provided largely negative results, so far. Here, the authors present a machine learning framework that quantifies potential associations between the pathology of AD severity and gene-based molecular mechanisms to enable drug repurposing.

The benefit of repetitive PIPAC specifically in CPM patients has yet to be demonstrated in terms of oncological and functional outcomes. The aim of this study was to evaluate the outcome of patients with non-resectable colorectal peritoneal metastases (CPM) treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). We conducted an analysis of a prospective single-center database of all CPM patients who underwent PIPAC with oxaliplatin 92 mg/m2 body surface (PIPAC-Ox). The outcome criteria were adverse events (Common Terminology Criteria for Adverse Events version 4.0), Peritoneal Regression Grading Score (PRGS), and survival. Overall, 102 patients with a median age of 64 years (33–88) were scheduled for PIPAC-Ox. Access to the abdominal cavity for the first application failed in 22/102 (21.6%) patients. A total of 185 PIPACs were performed, with 26/102 (25.5%), 20/102 (19.6%), 17/102 (16.7%), and 17/102 (16.7%) patients undergoing one, two, three, and four or more PIPACs, respectively. Perioperative overall morbidity/mortality Grade I–V occurred in 14 (7.6%), 29 (15.8%), 6 (3.2%), 1 (0.5%), and 1 (0.5%) patient without significant differences between each cycle. Of 27 patients who underwent three or more PIPACs, 20/102 (19.6%) had major/complete CPM regression (PRGS 1–2). In a multivariate analysis, independent predictive factors for > 12 months’ survival following the first PIPAC-Ox administration were three or more PIPACs (odds ratio [OR] 4.5, 95% confidence interval [CI] 1.35–15.2; p = 0.014) and younger patient age (OR 1.058, 95% CI 1.00–1.12; p = 0.039). Repetitive PIPAC-Ox for CPM patients, alone or combined with perioperative systemic chemotherapy, is feasible. Our data suggest that three or more consecutive PIPAC-Ox cycles for advanced CPM can improve survival.

The new guideline on organized cancer screening programs has been in force in Germany since January 1st, 2020. The guideline has amended earlier recommendations on cytological examinations, which were previously carried out annually during screening. The guidelines-based recommendations on the appropriate follow-up for preinvasive and invasive lesions of the uterine cervix and endometrium are briefly outlined and differentiated from screening cytology and Pap/HPV co-testing as described in the guideline on organized cancer screening programs (oKFE-RL).

Seltene Mammatumoren mit einem Anteil

Die Ubergangsphase der Perimenopause mit ihren assoziierten hormonellen Veranderungen fuhrt unter anderem zu einer Veranderung der Stimmungslage bei betroffenen Frauen. Das Risiko einer Depression verdreifacht sich in der Peri- und Postmenopause. Vasomotorische Beschwerden und hohe Testosteronserumspiegel, nicht jedoch hohe oder niedrige Ostrogenserumspiegel sind unabhangige Risikofaktoren fur das Auftreten depressiver Symptome. Eine perimenopausale Hormontherapie mit Ostrogenen oder Ostrogenen und Gestagenen kann bei jenen Frauen in Betracht gezogen werden, bei denen psychische Symptome als Folge der Menopause auftreten oder sich in zeitlichem Zusammenhang mit der Menopause verschlechtern. Weibliche Sexualsteroide haben einen neuroprotektiven Einfluss. Eine reduzierte Lebenszeitexposition mit Ostradiol, beispielsweise durch eine spate Menarche oder fruhe Menopause, erhoht das Risiko fur demenzassoziierte Symptome sowie die neuropathologische Diagnose einer Demenz vom Alzheimer-Typ. Es gibt allerdings in der Literatur keine Daten mit starker Evidenz fur einen vorteilhaften Effekt hinsichtlich der Demenz bei Frauen mit naturlicher Menopause, die eine peri- oder postmenopausale Hormonersatztherapie vor dem 65. Lebensjahr anwenden.

Patientinnen, die an einem Mamma‑, Endometrium- oder Ovarialkarzinom erkrankten und wahrend adjuvanter Therapiemasnahmen bzw. nach Abschluss der Primarbehandlung unter Symptomen bzw. Folgen einer naturlichen bzw. therapiebedingten Ovarialfunktionseinschrankung leiden, erwagen eine Hormonersatztherapie („hormone replacement therapy“ [HRT]). Da die Erkrankungen hormonabhangig sind, steigert eine HRT moglicherweise das Rezidivrisiko. Die Datenlage zur Beurteilung der onkologischen Sicherheit einer HRT nach den oben angefuhrten Malignomerkrankungen ist insgesamt unzureichend. Metaanalysen zeigen uberwiegend keine Steigerung des Rezidivrisikos. Aufgrund der Anzahl der eingeschlossenen Patientinnen und anderer methodischer Schwachen sind die Studien jedoch unzureichend, um die Sicherheit einer HRT nach abgeschlossener onkologischer Therapie zu etablieren. Fur die drei Malignome liegen jeweils auch randomisierte Studien vor, die bei einer HRT-Anwendung nach Mammakarzinom ein erhohtes Rezidivrisiko ergaben, fur das Endometriumkarzinom keine Risikosteigerung und fur das Ovarialkarzinom sogar eine Verbesserung des Uberlebens zeigten. Alle Studien haben jedoch eine Reihe von methodischen Schwachen, sodass die Sicherheit der HRT nach den genannten Malignomen unklar ist. Eine HRT nach Mamma‑, Endometrium- oder Ovarialkarzinomerkrankung ist daher grundsatzlich kontraindiziert. Bei ausgepragter Beeintrachtigung der Lebensqualitat durch klimakterische Symptome kann sie im Einzelfall nach entsprechender Aufklarung durchgefuhrt werden.

Die Hormonersatztherapie (HRT) ist die wirksamste Behandlungsform klimakterischer Beschwerden, birgt aber eine Reihe von Risiken, unter denen dasjenige fur Brustkrebs zu den relevantesten zahlt. Die in Studien beobachteten Effekte einer HRT sind unterschiedlich, hangen von den enthaltenen Ostrogenen bzw. Gestagenen ab und sind zeitabhangig. Die Wirkungen der Steroide werden uber unterschiedliche Subtypen von Ostrogen- und Progesteronrezeptoren vermittelt. In unterschiedlichen Situationen kann eine HRT gegensatzliche Effekte hervorrufen. Eine Ostrogentherapie (ET) fuhrt zu keiner oder nach Langzeitanwendung uber mehrere Jahre zu einer geringgradigen Steigerung des Brustkrebsrisikos. Die kombinierte HRT mit Ostrogenen und Gestagenen (EPT) steigert das Brustkrebsrisiko nach kurzeren Anwendungszeiten. Der Gestagenanteil spielt eine relevante Rolle fur das Ausmas der Risikosteigerung. Nach behandeltem Mammakarzinom ist eine HRT kontraindiziert. Sie kann in Ausnahmesituationen erwogen werden.

The role of adjuvant radiotherapy and/or chemotherapy in the primary treatment of endometrial cancer with a high risk of recurrence has still not been conclusively determined. The results of 3 large randomized controlled studies on different aspects of this issue have been published in full in recent months, and the relevant results are analyzed here. Die Rollen von adjuvanter Radio- und/oder Chemotherapie in der Primärbehandlung des Endometriumkarzinoms mit hohem Rezidivrisiko sind nicht eindeutig geklärt. In den letzten Monaten wurden Vollpublikationen von 3 großen randomisierten kontrollierten Studien zu verschiedenen Aspekten dieser Problematik vorgelegt, die im Kontext analysiert werden. peerReviewed

Die S3-Leitlinie „Peri- und Postmenopause – Diagnostik und Therapie“ beinhaltet Handlungsanweisungen und Empfehlungen fur die Hormonersatztherapie (HRT) zur Behandlung klimakterischer Beschwerden, die von etwa 50 % der perimenopausalen Frauen und bei 30–80 % der postmenopausalen Frauen angegeben werden. Eine HRT mit Ostrogenen (ET) oder Ostrogenen und Gestagenen (EPT) wird als symptomatische Therapie zur Behandlung von klimakterischen Beschwerden mit klinisch relevanter Beeintrachtigung der Lebensqualitat eingesetzt. Alternativ konnen auch Isoflavone, Cimicifuga-Praparate, Serotonin- bzw. Serotonin-Noradrenalin-Wiederaufnahmehemmer, Clonidin, Gabapentin oder kognitive Verhaltenstherapie angewendet werden. Im vorliegenden Artikel werden Effektivitat und Sicherheit sowie Nebenwirkungen und systemische Wirkungen dieser unterschiedlichen Therapieformen entsprechend den Vorgaben der S3-Leitlinie „Peri- und Postmenopause – Diagnostik und Therapie“ dargestellt.

Die Hormonersatztherapie (HRT) bei peri- und postmenopausalen Frauen ist die effektivste Behandlung klimakterischer Beschwerden und gehort zu den am haufigsten eingesetzten endokrinen Therapien. Bei der Verordnung sind Nutzen und Risiken gegeneinander abzuwagen. Zu den potenziellen Risiken gehort das erhohte Krebsrisiko. Risikomodifikationen betreffen uberwiegend das Mamma-, das Endometrium- und das Ovarialkarzinom. Eine HRT kann das Brustkrebsrisiko erhohen, abhangig von der Zusammensetzung der eingesetzten Praparate und der Anwendungsdauer. Eine HRT mit Ostrogenen und Gestagenen (EPT) erhoht das Risiko starker als eine Ostrogenmonotherapie (ET). Bei einer EPT sind Anwendungszeiten von ca. 5 Jahren erforderlich, um eine geringe Risikosteigerung nachzuweisen. Bei der ET ist die Risikosteigerung erst nach langeren Anwendungszeiten nachweisbar. Eine ET kann bei postmenopausalen Frauen zu einem erhohten Endometriumkarzinomrisiko fuhren. Daher soll bei nichthysterektomierten Frauen grundsatzlich nur eine EPT mit ausreichend langer Gestagenanwendung erfolgen. Eine Anwendungszeit einer EPT bis zu 5 Jahren erhoht das Endometriumkarzinomrisiko nicht. Langerfristige sequenzielle Therapien konnen zu einer Erhohung des Endometriumkarzinomrisikos fuhren. Fur die mehr als funfjahrige kontinuierlich kombinierte EPT sind die Studienergebnisse diesbezuglich kontrovers. Der Zusammenhang zwischen einer HRT und dem Ovarialkarzinomrisiko wurde in der Vergangenheit kontrovers beurteilt. Eine jungere Metaanalyse zeigt, dass eine HRT (ET bzw. EPT) das Risiko erhohen kann. Aufgrund der geringen Inzidenz des Ovarialkarzinoms ist das absolute Risiko relativ gering. Die differenzierte Aufklarung der Patientin uber o. a. Risiken ist vor Anwendung einer HRT zur Behandlung klimakterischer Beschwerden zu beachten. Sie ist in die Entscheidungsfindung miteinzubeziehen und bei der Durchfuhrung einer HRT zu berucksichtigen.

Chronic ectopic pregnancy (CEP) is a variant of ectopic pregnancy (EP) characterized by low or absent serum human chorionic gonadotropin (hCG) levels, resistance to methotrexate (MTX), and an adnexal mass with fibrosis, necrosis, and blood clots due to repeated and gradual fallopian tube wall disintegration. CEP may complicate the course of patients with EP and is difficult to diagnose. The case of a 36-year-old woman with EP, low serum hCG levels, a small echogenic adnexal mass, and resistance to MTX is presented. Salpingectomy was performed and histology demonstrated CEP with fibrosis, necrosis, and a hematocele within degenerated chorionic villi. In a database search, 19 case reports, 3 case–control studies, and 3 case series describing 399 patients with CEP were identified. Serum hCG was negative in 40/124 cases (32%) with reported levels of serum hCG. The most common presenting symptom was abdominal pain (284/399 [71%]), followed by irregular vaginal bleeding (219/399 [55%]), and fever (20/399 [5%]). 73/399 (18%) women were asymptomatic. An adnexal mass was seen in 144/298 (48%) cases with perioperative ultrasound examination and with a mean largest diameter of 6.8 cm. Data on treatment modalities and outcomes were available for 297 women. Of these, 89% underwent surgery as first-line therapy. Laparoscopy was performed in most cases. MTX was the first-line therapy in a minority of cases. Complete resolution was achieved by first-line therapy in 287/297 (97%) cases. Adverse events were reported in 218 patients with CEP. Among those, adverse events ≥ grade 3 were seen in 186/218 (85%) cases. There was no case of treatment-related mortality. CEP is a variant of EP with low or absent trophoblast activity. A prolonged clinical course is typical and surgery is the mainstay of treatment.

Acute colonic pseudo-obstruction or Ogilvie’s syndrome (OS) is a rare form of postsurgical or posttraumatic complication. OS rarely occurs in the postoperative course of gynecologic and obstetric patients and is difficult to diagnose. We present the case of an 83-years-old patient with carcinosarcoma of the uterus who developed OS with non-obstructive dilation of the right hemicolon and intraabdominal compression after total abdominal hysterectomy, omentectomy, and lymphadenectomy. Laparotomy with colonic decompression and abdominal dressing was performed. Subsequently, the patient developed pneumonia and peritonitis and died due to septic shock. We identified 49 case reports and 10 case series describing 17 gynecologic (cervical cancer, n = 2; carcinosarcoma of the uterus, n = 1; benign gynecologic condition, n = 14) and 76 obstetric patients (cesarean section, n = 66; OS during pregnancy or after vaginal delivery, n = 10). Outcome data were available for 59 patients. First-line treatment was conservative in 22/59 (37%) cases, laparotomy with decompression or colon resection was performed in 20/59 (34%) cases, endoscopic decompression in 12/59 (20%) cases, and i.v. neostigmine in 4/59 (7%) cases. Resolution was achieved in 22/59 (37%) of patients. The most common second-line treatment was right hemicolectomy. Adverse events grade 3 and 4 were observed in 8/59 and 31/59 patients (together 66%), respectively, mortality was 3/59 (5%). OS is a rare postoperative complication of gynecologic and obstetric patients with a good prognosis, but a high morbidity. Pregnancy seems to be a predisposing factor for OS. Conservative treatment is a successful first-line approach.

Cytoreductive surgery (CRS) is an appropriate treatment for selected patients with endometrial cancer (EC)-derived peritoneal metastases (PM). Hyperthermic intraperitoneal chemotherapy (HIPEC) may enhance the therapeutic efficacy of CRS in these patients. We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials and case reports reporting on the safety and efficacy of CRS and HIPEC in patients with EC-derived PM. Eight publications reporting on 68 patients were identified. The mean patient age was 57.1 years and the mean time from initial treatment of EC to CRS and HIPEC was 22.3 months. 41/64 patients had adenocarcinomas, type II cancers were present in 23/64 patients. The mean peritoneal carcinomatosis index (PCI) was 16.7. A complete surgical resection CC-0 was achieved in 44/63 (70%) patients. The chemotherapy regimens used for HIPEC were variable, but all included cisplatin, administered either alone (39/68 patients) or combined with doxorubicin or paclitaxel or mitomycin (29/68 patients). The duration of HIPEC was 60 min in 51/68 patients and 90 min in 17/68 patients. Mostly, the closed technique was used (55/68 patients). Adverse events grades 1/2, 3, and 4 were observed in 23/63, 12/63, and 6/63 patients, respectively. Treatment-associated mortality was 1% (1/63). After CRS and HIPEC, most patients received systemic chemotherapy (46/63 patients). Median disease-free and overall survival ranged from 7 to 18 and 12 to 33 months, respectively. In conclusion, CRS and HIPEC in EC with PM is safe and feasible. An additional therapeutic value of HIPEC is suggested, but prospective comparative trials are warranted.

Die S2k-Leitlinie der Deutschen (DGGG), Osterreichischen (OGGG) und Schweizerischen (SGGG) Gesellschaft fur Gynakologie und Geburtshilfe [1] hat evidenzbasiert die Diagnostik und Therapie des wiederholten Spontanaborts (WSA) anhand der aktuellen internationalen Literatur standardisiert. Dabei wurden die Empfehlungen und Statements in einem formalen Prozess erarbeitet und konsentiert. Insbesondere wurde auf die bekannten Risikofaktoren wie chromosomale, anatomische, endokrinologische, gerinnungsphysiologische, infektiologische und immunologische Storungen sowie die aktuellen Therapiemoglichkeiten eingegangen.

Calprotectin, a marker of acute and chronic inflammation, may play a role in pregnancy-associated disorders. We aimed to summarize available clinical data on calprotectin in pregnancy and to establish normal values of calprotectin during the course of pregnancy. We performed a systematic review of the databases PubMed and Cochrane Central Register of Controlled Trials to identify experimental and clinical evidence assessing the role of calprotectin in pregnancy. In addition, we performed a prospective cohort study assessing serum and urine calprotectin throughout pregnancy. We identified 17 studies investigating 1638 pregnant women, 151 newborns, and 99 non-pregnant controls, measuring calprotectin in different compartments. Calprotectin was present in meconium and elevated in fecal samples of pregnant women with active inflammatory bowel disease. In women with pregnancy-induced hypertension, mild and severe preeclampsia (PE), calprotectin was significantly elevated in maternal plasma and serum, but not in fetal serum, amniotic fluid, and umbilical cord blood. For the cohort study, we recruited 196 pregnant women. PE and concomitant renal disease were present in 6/196 (3%) and 11/196 (5.6%) of women, respectively. Throughout pregnancy, median serum and urine levels of calprotectin largely exceed reported concentrations of the healthy non-pregnant population, but showed no significant variations between trimesters 1–3 and post-partum. Calprotectin in serum was correlated with systolic blood pressure and in urine with leukocytes and total protein. No significant differences were found in subgroup analyses of smokers vs. non-smokers, PE vs. none, and renal disease (kidney stones, reflux) vs. none. Calprotectin concentrations in amnion fluid and stools serve as potential indicators of inflammatory states during pregnancy. Urinary calprotectin concentrations are continuously high during pregnancy and show no significant variations between trimesters 1–3 and post-partum.

Introduction: Retinopathy of prematurity (ROP) remains an important cause for preventable blindness. Aside from gestational age (GA) and birth weight, risk factor assessment can be important for determination of infants at risk of (severe) ROP. Methods: Prospective, multivariable risk-analysis study (NEDROP-2) was conducted, including all infants born in 2017 in the Netherlands considered eligible for ROP screening by pediatricians. Ophthalmologists provided data of screened infants, which were combined with risk factors from the national perinatal database (Perined). Clinical data and potential risk factors were compared to the first national ROP inventory (NEDROP-1, 2009). During the second period, more strict risk factor-based screening inclusion criteria were applied. Results: Of 1,287 eligible infants, 933 (72.5%) were screened for ROP and matched with the Perined data. Any ROP was found in 264 infants (28.3% of screened population, 2009: 21.9%) and severe ROP (sROP) (stage ≥3) in 41 infants (4.4%, 2009: 2.1%). The risk for any ROP is decreased with a higher GA (odds ratio [OR] 0.59 and 95% confidence interval [CI] 0.54–0.66) and increased for small for GA (SGA) (1.73, 1.11–2.62), mechanical ventilation >7 days (2.13, 1.35–3.37) and postnatal corticosteroids (2.57, 1.44–4.66). For sROP, significant factors were GA (OR 0.37 and CI 0.27–0.50), SGA (OR 5.65 and CI 2.17–14.92), postnatal corticosteroids (OR 3.81 and CI 1.72–8.40), and perforated necrotizing enterocolitis (OR 7.55 and CI 2.29–24.48). Conclusion: In the Netherlands, sROP was diagnosed more frequently since 2009. No new risk factors for ROP were determined in the present study, apart from those already included in the current screening guideline.

Purpose To compare resected cone mass and resection margin status when performing Large Loop Excision of the Transformation Zone (LLETZ) using video colposcopy (LLETZ-VC) versus a headlight (LLETZ-HL) in women with cervical dysplasia. Methods Prospective, randomised trial (monocentric) at a specialised cervical dysplasia unit in a University Hospital. Women with a biopsy-proven CIN2 + or persisting CIN1 or diagnostic LLETZ were recruited and randomised. LLETZ was performed either under video colposcopic vision or using a standard surgical headlight. The primary endpoint was resected cone mass. Secondary endpoints were the rate of involved margins, fragmentation of the specimen, procedure time, time to complete haemostasis (TCH), blood loss, pain, intra- and postoperative complications, and surgeon preference. Results LLETZ-VC and LLETZ-HL (109 women each) had comparable cone masses (1.57 [0.98–2.37] vs. 1.67 [1.15–2.46] grams; P = 0.454). TCH was significantly shorter in the LLETZ-VC arm (60 [41–95.2] vs. 90 [47.2–130.2] seconds; P = 0.008). There was no statistically significant difference in involved resection margins (6/87 [6.5%] vs. 16/101 [13.7%], P = 0.068) and postoperative complications (13/82 [13.7%] vs. 22/72 [23.4%], P = 0.085). Patient-reported outcomes favoured LLETZ-VC with a lower use of analgesics (6/80 [7.0%] vs. 17/87 [16.3%]; P = 0.049). However, LLETZ-VC was more difficult to perform with significantly lower ratings for handling (7 [5–9] vs. 9 [8–10]; P P Conclusion Intraoperative video colposcopy for LLETZ has minimal benefits at the cost of surgeons’ satisfaction. Clinical trial registration NCT04326049 (ClinicalTrials.gov).

Aim The aim of the interdisciplinary S3-guideline Perimenopause and Postmenopause – Diagnosis and Interventions is to provide help to physicians as they inform women about the physiological changes which occur at this stage of life and the treatment options. The guideline should serve as a basis for decisions taken during routine medical care. This short version lists the statements and recommendations given in the long version of the guideline together with the evidence levels, the level of recommendation, and the strength of consensus. Methods The statements and recommendations are largely based on methodologically high-quality publications. The literature was evaluated by experts and mandate holders using evidence-based medicine (EbM) criteria. The search for evidence was carried out by the Essen Research Institute for Medical Management (EsFoMed). To some extent, this guideline also draws on an evaluation of the evidence used in the NICE guideline on Menopause and the S3-guidelines of the AWMF and has adapted parts of these guidelines. Recommendations Recommendations are given for the following subjects: diagnosis and therapeutic interventions for perimenopausal and postmenopausal women, urogynecology, cardiovascular disease, osteoporosis, dementia, depression, mood swings, hormone therapy and cancer risk, as well as primary ovarian insufficiency.

Background Bone-targeted agents (BTAs) are widely used in the management of patients with bone metastases from solid tumors. Knowledge of the impact of their routine care use on patient-reported pain and bone pain-related quality of life (QoL) is limited. Methods This real world, cross-sectional study enrolled patients over a 3-month period through oncologists across Switzerland. Patients were ≥ 18 years, had solid tumors and at least one bone metastasis, and received routine care for bone metastases. Physicians provided data on BTA-related practices, risk of bone complications and BTA regimen. Patients completed questionnaires about pain (BPI-SF), general and bone pain-related QoL (FACT-G, FACT-BP) and treatment satisfaction (FACIT-TS-G). Results Eighteen sites recruited 417 patients. Based on the FACT-BP, 42% of the patients indicated not having bone pain. According to the BPI-SF, 28% reported no, 43% mild, 14% moderate, and 15% severe pain, respectively. Patients not treated with a BTA had better overall QoL (FACT-G: p = 0.031) and bone pain-related QoL (FACT-BP, p = 0.007) than those treated with a BTA. All pain and other QoL scales did not differ between groups. Patients perceived at ‘low risk of bone complications’ by their physician not receiving a BTA reported less pain and better QoL than those considered at ‘low risk’ but receiving BTA treatment or those considered at ‘high risk’ regardless of BTA treatment. Overall satisfaction with the treatment was good; almost 50% of patients reporting that they were completely satisfied. Conclusions Overall, pain and QoL did not differ according to BTA treatment or physicians’ risk perception. Patient with low risks not receiving BTA treatment reported least pain and highest QoL scores. These results may suggest that treating physicians assess bone complication risk appropriately and treat patients accordingly, but they need to be confirmed by objective determination of longitudinal skeletal complication risk.

Background PIPAC is a new treatment modality for peritoneal cancer which has been practiced and evaluated until very recently by few academic centers in a highly standardized manner. Encouraging oncological outcomes and the safety profile have led to widespread adoption. The aim of this study was to assess current PIPAC practice in terms of technique, treatment and safety protocol, and indications. Methods A standardized survey with 82 closed-ended questions was sent online to active PIPAC centers which were identified by help of PIPAC training centers and the regional distributors of the PIPAC-specific nebulizer. The survey inquired about center demographics (n = 8), technique (n = 34), treatment and safety protocol (n = 34), and indications (n = 6). Results Overall, 62 out of 66 contacted PIPAC centers answered the survey (response rate 93%). 27 centers had performed >60 PIPAC procedures. A consensus higher than 70% was reached for 37 items (50%), and higher than 80% for 28 items (37.8%). The topics with the highest degree of consensus were safety and installation issues (93.5% and 80.65%) while chemotherapy and response evaluation were the least consensual topics (63.7 and 59.6%). The attitudes were not influenced by volume, PIPAC starting year, type of activity, or presence of peritoneal metastases program. Conclusion Homogeneous treatment standards of new techniques are important to guarantee safe implementation and practice but also to allow comparison between cohorts and multi-center analysis of merged data including registries. Efforts to avoid diversification of PIPAC practice include regular update of the PIPAC training curriculum, targeted research and a consensus statement.

Aims This is an official interdisciplinary guideline published and coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The guideline was developed for use in German-speaking regions and is backed by numerous professional societies and organizations. The aim of this guideline is to provide an evidence- and consensus-based overview of the diagnostic approach and the management of hormonal contraception based on a systematic evaluation of the relevant literature. Methods To compile this S3-guideline, a systematic search for evidence was carried out in PubMed and the Cochrane Library to adapt existing guidelines and identify relevant reviews and meta-analyses. A structured evaluation of the evidence was subsequently carried out on behalf of the Guidelines Commission of the DGGG, and a structured consensus was achieved based on consensus conferences attended by representative members from the different specialist societies and professions. Recommendations Evidence-based recommendations about the advice given to women requesting contraception were compiled. The guideline particularly focuses on prescribing contraceptives which are appropriate to womenʼs individual needs, take account of her personal circumstances, and have few or no side effects.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new locoregional treatment for peritoneal carcinomatosis. The safety and efficacy of PIPAC have been documented in case reports, retrospective cohort studies, and prospective clinical phase I and phase II trials in patients with peritoneal carcinomatosis derived from various malignancies such as ovarian, gastric, and colon cancer. PIPAC is an alternative to palliative systemic chemotherapy based on its locoregional cytotoxic properties as well as its positive effects on the patients’ quality of life. A number of studies looked at quality-of-life issues during PIPAC treatment and observed a stabilization and/or improvement of overall quality of life, role functioning, social functioning, physical performance, and cognitive performance as well as gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Based on these observations, it may be concluded that, as a palliative treatment of peritoneal carcinomatosis, PIPAC has positive effects on multiple levels of quality of life.

Simple Summary Tamoxifen, an antiestrogen, is a potent drug to treat and prevent hormone dependent breast cancer. As it has low toxicity and is widely available, tamoxifen has become one of the most frequently prescribed anticancer drugs worldwide. A major side effect of tamoxifen is to increase the risk of uterine corpus cancer (endometrial cancer). This happens after long-term (>2 years) application, especially in postmenopausal women with preexisting pathologies in the uterus. On the other hand, tamoxifen is an efficacious treatment for certain forms of advanced endometrial cancer, thus making it a Janus-headed drug that can support the development of endometrial cancer on one hand and be used as a remedy for this disease on the other. This article reviews the clinical data on these controversial effects of tamoxifen and the possible explanations. Abstract Tamoxifen is a selective estrogen receptor modulator used for the treatment and prevention of estrogen receptor (ER)—positive breast cancer. However, tamoxifen increases the risk of endometrial cancer (EC) by about 2–7 fold, and more aggressive types of EC with poor prognoses are observed in tamoxifen users. On the other hand, tamoxifen is an efficacious treatment for advanced or recurrent EC with low toxicity. The differential agonistic or antagonistic effects of tamoxifen on ERα are explained by the tissue-specific expression profiles of co-activators and co-repressors of the receptor. The estrogen-agonistic effect of tamoxifen in endometrial cancers can also be explained by the expression of G-protein coupled estrogen receptor 1 (GPER-1), a membrane-bound estrogen receptor for which tamoxifen and other “antiestrogens” are pure agonists.

Endometrial cancer (EC) is the most common cancer affecting the female reproductive organs in higher-income states. Apart from reproductive factors and excess weight, genetic predisposition is increasingly recognized as a major factor in endometrial cancer risk. Endometrial cancer is genetically heterogeneous: while a subgroup of patients belongs to cancer predisposition syndromes (most notably the Lynch Syndrome) with high to intermediate lifetime risks, there are also several common genomic polymorphisms contributing to the spectrum of germline predispositions. Germline variants and somatic events may act in concert to modulate the molecular evolution of the tumor, where mismatch-repair deficiency is common in endometrioid endometrial tumors whereas homologous recombinational repair deficiency has been described for non-endometrioid endometrial tumors. In this review, we will survey the currently known genomic predispositions for endometrial cancer and discuss their relevance for clinical management in terms of counseling, screening and novel treatments.

Introduction In connection with the reorganisation of cervical carcinoma screening, the importance of colposcopy as an integral part of the planned series of clarification testing will greatly increase. Quality standards for performing the colposcopic examination should therefore be defined in detail. A precondition for this is surveying the current standard in clinical practice. The objective of this study was to evaluate the current practice of colposcopy and conisation in Germany by means of a questionnaire aimed at gynaecologists who perform colposcopies in order to document the actual therapeutic standard of treatment of cervical dysplasia. Materials and Methods Gynaecologists were invited via e-mail or during events to participate in a web-based survey. The questionnaire contained 38 questions on management before, during and after the examination as well as questions on the technical implementation of colposcopy and conisation. Results From February 2018 to April 2018, 961 e-mails were sent. A response was received in 197 cases (response rate 20.5%). Responses were received for another 40 questionnaires during events (response rate approx. 80%). After taking the inclusion criteria into account, 160 questionnaires were evaluated. The majority of those surveyed take an average of 2 cervical biopsies (67.3%) and nearly all of those surveyed (94.5%) do not use any local anaesthetic. As a standard method for removing cervical precancerous cells, most of the physicians surveyed perform a loop excision with the electrosurgical loop (91.2%) under colposcopic visualisation (61.2%) under general anaesthesia (92.5%). Postoperative bleeding prophylaxis by means of tamponade is performed only in 27.6% of all cases. Conclusion A differential colposcopy with two colposcopically targeted biopsies and treatment with the electrosurgical loop are the methods most frequently used by clinicians who perform colposcopy in Germany. A uniform procedure should be defined in detail within the scope of directives or guidelines.

Clinical trials of novel therapeutics for Alzheimer’s Disease (AD) have consumed a large amount of time and resources with largely negative results. Repurposing drugs already approved by the Food and Drug Administration (FDA) for another indication is a more rapid and less expensive option. Repurposing can yield a useful therapeutic and also accelerate proof of concept studies that ultimately lead to a new molecular entity. We present a novel machine learning framework, DRIAD (DrugRepurposing InAD), that quantifies potential associations between the pathology of AD severity (the Braak stage) and molecular mechanisms as encoded in lists of gene names. DRIAD was validated on gene lists known to be associated with AD from other studies and subsequently applied to evaluate lists of genes arising from perturbations in differentiated human neural cell cultures by 80 FDA-approved and clinically tested drugs, producing a ranked list of possible repurposing candidates. Top-scoring drugs were inspected for common trends among their nominal molecular targets and their “off-targets”, revealing a high prevalence of kinases from the Janus (JAK), Unc-51-like (ULK) and NIMA-related (NEK) families. These kinase families are known to modulate pathways related to innate immune signaling, autophagy, and microtubule formation and function, suggesting possible disease-modifying mechanisms of action. We propose that the DRIAD method can be used to nominate drugs that, after additional validation and identification of relevant pharmacodynamic biomarker(s), could be evaluated in a clinical trial.

Background Loop electrosurgical excision procedure may be performed under local anesthesia or general anesthesia, and practice patterns differ worldwide. No randomized head-to-head comparison has been published to confirm or refute either practice. Objective This study aimed to compare loop electrosurgical excision procedure under local anesthesia vs general anesthesia regarding patient satisfaction and procedure-related outcomes such as rates of involved margins, complications, pain, and blood loss. Study Design Consecutive women referred to our colposcopy unit were recruited. Loop electrosurgical excision procedure was performed under local anesthesia with 4 intracervical injections of bupivacaine hydrochloride 0.5% or under general anesthesia with fentanyl, propofol, and a laryngeal mask with sevoflurane maintenance. The primary endpoint was patient satisfaction assessed on the day of surgery and 14 days thereafter using a Likert scale (score 0–100) and a questionnaire. Secondary endpoints included rates of involved margins, procedure-related complications, pain, blood loss, and surgeon preference. Results were compared using nonparametric and chi-square tests. Results Between July 2018 and February 2020, we randomized 208 women, 108 in the local anesthesia arm and 100 in the general anesthesia arm. In the intention-to-treat analysis, patient satisfaction did not differ between the study groups directly after surgery (Likert scale 100 [90–100] vs 100 [90–100]; P=.077) and 14 days thereafter (Likert scale 100 [80–100] vs 100 [90–100]; P=.079). In the per-protocol analysis, women in the local anesthesia arm had significantly smaller cone volumes (1.11 cm3 [0.70–1.83] vs 1.58 cm3 [1.08–2.69], respectively; P Conclusion Loop electrosurgical excision procedure under local anesthesia is equally well tolerated and offers patient-reported and procedure-related benefits over general anesthesia, supporting the preferred practice in some institutions and refuting the preferred practice in others.

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose Using evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patientʼs quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal extent of surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy if required. An evidence-based optimal use of different therapeutic modalities should improve the survival rates and quality of life of these patients. This S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources included reviews of evidence, which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one part of the guideline. Identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then subsequently modified during structured consensus conferences and/or additionally amended online using the DELPHI method, with consent between members achieved online. The guideline report is freely available online. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of endometrial cancer including precancers and early endometrial cancer as well as recommendations on palliative medicine, psycho-oncology, rehabilitation, patient information and healthcare facilities to treat endometrial cancer. The management of precancers of early endometrial precancerous conditions including fertility-preserving strategies is presented. The concept used for surgical primary therapy of endometrial cancer is described. Radiotherapy and adjuvant medical therapy to treat endometrial cancer and uterine carcinosarcomas are described. Recommendations are given for the follow-up care of endometrial cancer, recurrence and metastasis. Palliative medicine, psycho-oncology including psychosocial care, and patient information and rehabilitation are presented. Finally, the care algorithm and quality assurance steps for the diagnosis, therapy and follow-up of patients with endometrial cancer are outlined.

The data on the adjuvant therapy of endometrial cancer (EC) are inconsistent. Recent studies of this topic such as PORTEC-3, GOG-258 and GOG-249 investigated the value of adjuvant radiotherapy, adjuvant chemotherapy and combined adjuvant chemoradiotherapy followed by chemotherapy in patients with endometrial cancer and an increased risk of recurrence. With this statement, the Uterus Committee of the Gynaecological Oncology Working Group (AGO) wishes therefore to interpret the new data and discuss them against the background of the new S3 guideline "Diagnosis, treatment and follow-up of patients with endometrial cancer".Die Datenlage zur adjuvanten Therapie des Endometriumkarzinoms (EC) ist widersprüchlich. Neue Studien zu diesem Thema wie PORTEC-3, GOG-258 und GOG-249 untersuchten die Wertigkeit der adjuvanten Strahlentherapie, der adjuvanten Chemotherapie und der kombinierten adjuvanten Strahlenchemotherapie gefolgt von einer Chemotherapie bei Patientinnen mit Endometriumkarzinom und einem erhöhten Rezidivrisiko. Die Kommission Uterus der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) möchte daher mit dieser Stellungnahme die neuen Daten interpretieren und vor dem Hintergrund der neuen S3-Leitlinie „Diagnostik, Therapie und Nachsorge der Patientinnen mit Endometriumkarzinom“ diskutieren.

Im April 2018 erschien die erste deutsche interdisziplinare S3-Leitlinie fur die Diagnostik, Therapie und Nachsorge der Patientinnen mit Endometriumkarzinom. Dieser Beitrag ist die Zusammenfassung des Kapitels 3: „Epidemiologie und Risikofaktoren, Pravention des Endometriumkarzinoms“ und des Kapitels 10: „Hereditare Endometriumkarzinome“ mit dem Ziel, dem Leser eine klinisch orientierte Kurzfassung an die Hand zu geben. Dargestellt sind die Statements und Empfehlungen zur Epidemiologie und den Risikofaktoren des Endometriumkarzinoms sowie zur Diagnose und Therapie hereditarer Endometriumkarzinome.

Systemic chemotherapy is not effective in patients with peritoneal carcinomatosis (PC) and only a minority of affected patients is eligible for cytoreductive surgery. Intraperitoneal chemotherapy may provide a therapy alternative for these patients. We performed a systematic review of clinical and experimental evidence on the safety and efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with PC and provide clinical recommendations based on the available evidence. Fifty-eight reports were identified, categorized as experimental (18 reports), clinical (28 reports), and other articles (14 reports). Experimental studies demonstrated improved tissue penetration and peritoneal coverage. The 28 clinical studies reported on 3515 procedures in 1547 patients with PC of various primary tumors with 16 of these studies reporting on patients with ovarian cancer. Toxicity was manageable. Based on 1197 patients in 22 studies, adverse events CTCAE grades 1, 2, 3, 4, and 5 were observed in 537 (45%), 167 (14%), 83 (7%), 10 (0.8%), and 19 (1.6%) cases, respectively. In a pooled analysis, the objective tumor response rate was 69% and the mean overall survival duration was 13.7 months. No significant hepatic, renal, or hematologic toxicity was described. PIPAC maintained and/or improved quality of life, as reported in 10 studies with 396 patients. Available evidence from controlled trials (phase I and phase II) and retrospective cohort studies in > 1500 patients unequivocally demonstrates that PIPAC is feasible, safe, and effective. PIPAC maintains quality of life in patients with recurrent cancer and PC. PIPAC is as evidence-based as any other treatment in women with ovarian cancer and PC beyond the third line of systemic chemotherapy and can be recommended in this indication.

Zusammenfassung Zielsetzung Untersucht werden soll der leitliniengerechte Einsatz des Cardiotokogramms (CTG), sowohl ante partum als auch sub partu, im internationalen Vergleich. Material und Methoden Verglichen wurden die Leitlinien verschiedener Länder (Deutschland, Kanada, Großbritannien, USA, Sri Lanka und Australien) sowie die Empfehlungen der Fédération Internationale de Gynécologie et d̛Obstétrique (FIGO). Gegenübergestellt wurden die Empfehlungen zum Einsatz des CTG sowohl ante partum als auch sub partu. Ergebnisse CTG ante partum: Es lässt sich feststellen, dass bei risikofreier Schwangerschaft der Einsatz des CTG in allen untersuchten Ländern nicht empfohlen wird. Bei Vorhandensein definierter Risikofaktoren für das fetale oder maternale Wohl wird der Einsatz des CTG hingegen empfohlen. Während die englische National Institute for Health and Care Excellence (NICE)-Guideline den Einsatz nur bei maternaler Hypertonie und Präeklampsie vorsieht, listet die Leitlinie der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) in Anlehnung an die Empfehlungen der Society of Obstetricians and Gynaecologists of Canada (SOGC) deutlich mehr Risikofaktoren auf. Sub partu: Subpartual unterscheiden sich die Empfehlungen von Land zu Land deutlich. In Deutschland wird der Einsatz des CTG ab der späten Eröffnungsperiode empfohlen. Die Leitlinien der anderen untersuchten Länder empfehlen während einer Nichtrisikoschwangerschaft vorrangig die Auskultation der fetalen Herzfrequenz unter der Geburt. Begründet wird dies mit der bisherigen Studienlage, die keinen Vorteil des CTG gegenüber der intermittierenden Auskultation erkennen lässt. Viel mehr ließ sich in den ausgewerteten Studien erkennen, dass es unter dem Einsatz des CTG zu einem Anstieg der Kaiserschnitterate kam. Anders sehen die Empfehlungen zur Anwendung des CTG unter der Geburt bei Risikoschwangerschaften aus. Hier wird in den Leitlinien der verglichenen Länder der Einsatz des CTG durchaus empfohlen, obwohl Unterschiede bezüglich der Indikation für den Einsatz des CTG festzustellen sind. Schlussfolgerung Die intermittierende Auskultation ist im Vergleich zum CTG zwar eine kostengünstigere Alternative, sie ist jedoch nicht kontinuierlich anwendbar und im Falle von Regressen schlechter nachvollziehbar als das CTG. Das CTG führt zu einer höheren Rate an Kaiserschnitten, bietet jedoch bei korrekter Anwendung Sicherheit für Fetus und Mutter sowie Rechtssicherheit für das geburtshilfliche Personal. Im internationalen Vergleich empfehlen die deutschen Leitlinien als einzige, trotz fehlender Evidenz, die CTG-Diagnostik ab der späten Eröffnungsperiode bei Nichtrisikoschwangerschaften.

OBJECTIVES The aim of the study was to compare two conization techniques, large loop excision of the transformation zone (LLETZ), and true cone biopsy electrode excision (TCBEE) in women with cervical dysplasia. MATERIALS AND METHODS In a randomized clinical trial, we compared LLETZ and TCBEE in women undergoing surgical treatment of cervical dysplasia in a 1:1 ratio. The primary endpoint was resection margin status (RMS), secondary endpoints were fragmentation of the surgical specimen, resection volume, operation time, time to complete hemostasis, blood loss, intraoperative and postoperative complications, surgeon's preference, and patient's postoperative pain, estimated by an 11-level visual analog scale (nVAS11), and a 5-level pictogram. RESULTS One hundred seventy-two women were randomized. No difference in the primary outcome, resection margin status, was observed between LLETZ and TCBEE (involved margins: 12/91 [13%] vs 7/81 [9%], respectively; p = .4). However, fragmentation rate (1 vs >1 fragment: 85 [93%] and 6 [7%] for LLETZ vs 63 [78%] and 18 [22%] for TCBEE; p = .004) and surgeon preference (nVAS11: 1 [0-2] vs 3 [1-7]; p < .001) favored LLETZ. Postoperative pain, however, was lower after TCBEE (nVAS11: 1 [0-3] vs 0 [0-2]; p = .02). The secondary outcome parameters resection volume, operation time, time to complete hemostasis, blood loss, intraoperative complications, and postoperative complications were not different between the study groups. In a multivariate analysis, age, body mass index, and parity did not affect the primary and secondary outcome parameters. CONCLUSIONS LLETZ and TCBEE are equally safe and efficacious procedures, but specimen fragmentation and surgeon preference favor loop excision.

Objective To test whether video colposcopy reduces anxiety among patients undergoing colposcopy. Methods In a prospective, randomized multicenter trial, we compared video colposcopy and no video colposcopy in a one-to-one ratio. Situation-specific anxiety was measured before (S1) and after (S2) colposcopy using the State-Trait Anxiety Inventory. The primary endpoint was the reduction of the situation-specific anxiety scores (ΔS=S2-S1). Secondary endpoints were pain during and 10 minutes after colposcopy, general unpleasantness, anxiety during colposcopy, satisfaction with the information about the procedure, and overall satisfaction (11-item visual analog scales). Analysis was by intention to treat. A sample size of 104 per group (n=208) was planned to achieve 80% power to detect a difference of 4.8 with a SD of 12.3 in the primary outcome. Results Between August 2016 and March 2017, 225 women were randomized. The mean ΔS was -10.3±11.3 SD in 111 women in the video colposcopy group and -10.3±11.0 SD in 105 women without video colposcopy (P=.50). The secondary endpoints pain during examination (median 2 [interquartile range 1-3] compared with 2 [1-4]; P=.91), pain 10 minutes after examination (1 [0-3] compared with 1 [0-2.5]; P=.24), general unpleasantness (3 [1-5] compared with 3 [1-5]; P=.90), anxiety during examination (3 [1-5] compared with 3 [1-5]; P=.61), satisfaction with the information about the procedure (10 [9-10] compared with 10 [9-10]; P=.88), and overall satisfaction (10 [9-10] compared with 10 [9-10]; P=.54) were also not different between the two study groups. In a multivariate linear regression analysis, study center (P=.028), body mass index (P=.033), and smoking status (P=.025) independently affected the reduction of anxiety. Conclusion Video colposcopy does not reduce anxiety in women undergoing colposcopy. Clinical trial registration ClinicalTrials.gov, NCT02697175.

The present review aimed to assess the safety and efficacy of thalidomide and lenalidomide, two immunomodulatory drugs with anti-angiogenic properties, in women with recurrent ovarian, fallopian tube, and primary peritoneal cancer. A systematic review of the literature was conducted whereby Medline and the Cochrane Central Register of Controlled Trials were searched using terms associated with thalidomide, lenalidomide, and recurrent ovarian, fallopian tube and primary peritoneal cancer. Published English language case reports, trials and studies that described the safety and efficacy of thalidomide or lenalidomide alone, or in combination with other drugs were reviewed. A total of 16 clinical studies involving 394 patients treated with thalidomide (n=188), lenalidomide (n=77) and 129 controls were identified, including five case reports (n=6), three case series (n=45), two phase I trials (n=27), four phase II trials (n=109), and two randomized phase III trials (n=207). In a pooled analysis of thalidomide investigated as a single drug, the overall clinical benefit rate was 43% (43/99) with a mean time to progression of 5.6 months. The response rate (complete response + partial response) was 25%. In a phase III trial, the combination of thalidomide and topotecan significantly increased the overall response rate compared with topotecan alone [14/30 (47%) vs. 8/39 (21%)]. In another phase III trial involving women with asymptomatic biochemical recurrence, compared with tamoxifen, thalidomide was not more effective. Lenalidomide was investigated in three phase I trials and in one phase II trial with an overall clinical benefit rate of 52% (34/65), and a mean time to progression of 4.6 months. The response rate (complete response + partial response) was 6%. Systemic toxicity of both drugs was noted in >77% of patients with pneumonitis/pneumonia, fatigue, neuropathy and venous thromboembolism reported as the most common side effects. Thalidomide and lenalidomide are moderately active in recurrent ovarian cancer. Thalidomide possesses synergistic effects with topotecan. The toxicity of both drugs is considerable and there is a greater amount of data available for thalidomide compared to lenalidomide.

Recurrent miscarriages are associated with strong distress in patients. In this paper, we describe - based on the S1 guideline of the German Society for Gynecology and Obstetrics (DGGG) - the evidence-based diagnostic and therapeutic options in patients with recurrent miscarriages.

Background: Young women with endometrial cancer (EC) have an increased risk of synchronous ovarian cancer. The prognosis of women with synchronous endometrial and ovarian cancer (SEOC) is good. A high proportion of affected women have hereditary non-polyposis colon cancer syndrome (HNPCC). Case presentation: We present the case of a 45-year-old woman with histologically proven endometrioid adenocarcinoma of the endometrium (pT1B, G2, R0 without lymphovascular space invasion). She underwent laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. Final histology revealed a synchronous bilateral endometrioid ovarian cancer (pT1A, G2, R0). HNPCC analysis by immunohistochemistry showed no microsatellite instability in MSH2, MSH6, MLH1, and PMS2. No adjuvant therapy was administered, clinical follow-up with regular gynecological examinations was recommended. In a systematic literature review, 2,904 cases of women with SEOC were identified with 1,035 (36%) of them being premenopausal or

The neonatal period, during which the initial gut microbiota is acquired, is a critical phase. The healthy development of the infant's microbiome can be interrupted by external perturbations, like antibiotics, which are associated with profound effects on the gut microbiome and various disorders later in life. The aim of this study was to investigate the development of intestinal microbiota and the effect of antibiotic exposure during the first three months of life in term infants. Fecal samples were collected from healthy infants and infants who received antibiotics in the first week of life at one week, one month, and three months after birth. Microbial composition was analyzed using IS-pro and compared between antibiotics-treated and untreated infants. In total, 98 infants, divided into four groups based on feeding type and delivery mode, were analyzed. At one week of age, samples clustered into two distinct groups, which were termed “settler types”, based on their Bacteroidetes abundance. Caesarean-born infants belonged to the low-Bacteroidetes settler type, but vaginally-born infants were divided between the two groups. The antibiotics effect was assessed within a subgroup of 45 infants, vaginally-born and exclusively breastfed, to minimize the effect of other confounders. Antibiotics administration resulted in lower Bacteroidetes diversity and/ or a delay in Bacteroidetes colonization, which persisted for three months, and in a differential development of the microbiota. Antibiotics resulted in pronounced effects on the Bacteroidetes composition and dynamics. Finally, we hypothesize that stratification of children's cohorts based on settler types may reveal group effects that might otherwise be masked.

Preventing the progression to acute respiratory distress syndrome (ARDS) in COVID-19 is an unsolved challenge. The involvement of T cell immunity in this exacerbation remains unclear. To identify predictive markers of COVID-19 progress and outcome, we analyzed peripheral blood of 10 COVID-19-associated ARDS patients and 35 mild/moderate COVID-19 patients, not requiring intensive care. Using multi-parametric flow cytometry, we compared quantitative, phenotypic and functional characteristics of circulating bulk immune cells, and SARS-CoV-2 S-protein reactive T cell between the two groups. ARDS patients demonstrated significantly higher S-protein reactive CD4+ and CD8+ T cells compared to non-ARDS patients. Of interest, comparison of circulating bulk T cells in ARDS patients to non-ARDS patients demonstrated decreased frequencies of CD4+ and CD8+ T cell subsets with activated memory/effector T cells expressing tissue migration molecule CD11a++. Importantly, survival from ARDS (4/10) was accompanied by a recovery of the CD11a++ T cell subsets in peripheral blood. Conclusively, data on S-protein reactive polyfunctional T cells indicate the ability of ARDS patients to generate antiviral protection. Furthermore, decreased frequencies of activated memory/effector T cells expressing tissue migratory molecule CD11a++ observed in circulation of ARDS patients might suggest their involvement in ARDS development and propose CD11a-based immune signature as a possible prognostic marker., Graphical Abstract, This study shows a strong SARS-CoV-2 S-protein T-cell response and decreased frequencies of activated memory/effector T-cells expressing migratory molecule CD11a++ in ARDS patients. The data suggest the involvement of the analyzed T-cell subsets in ARDS development and propose CD11a-based immune signature as a possible prognostic marker for COVID-19 progression.

Highlights • Implementation of guideline-recommended BTA practice is high among Swiss physicians. • Denosumab is the BTA of choice in Switzerland. • BTAs were widely administered (94.2%) according to a 3–4-weekly dosing regimen. • Bone pain and SRE incidence were low in patients with solid tumor bone metastases. • Low SRE incidence may indicate BTA efficacy and judicious BTA prescribing., Background Bone-targeted agents (BTAs) are widely used in the management of patients with bone metastases from solid tumors, but knowledge of their routine care use and the therapeutic implications remains limited. This non-interventional study aimed to characterize real-world BTA patterns of care in Switzerland. Materials and methods Non-interventional, cross-sectional study involving oncologists from across Switzerland who completed a Treating Physician questionnaire, providing data on their clinical setting and BTA-related practices, and a Patient Characteristics and Treatment questionnaire, providing data on their patients’ disease status, risk of bone complications, BTA regimen and related outcomes. Eligible patients were aged ≥ 18 years, with solid tumors and at least one bone metastasis and were receiving routine management at the participating physician's center over the 3-month study period. Results A total of 86 oncologists recruited 417 patients from across 18 centers in Switzerland (80% public hospitals; 20% private clinics). The majority of physicians (70.9%) reported prescribing BTAs in line with international guidelines; denosumab was the treatment of choice in 78.5% of patients. BTAs were widely administered (94.2%) according to a 3–4-weekly dosing regimen; 33.7% of physicians reported extending intervals to 12 weeks after an initial 2 years of treatment. Physicians appeared to use clinical judgement, as well as formal risk assessment, to guide treatment for symptomatic skeletal events. No association was seen between either BTA use, or risk of complications, and incidence of skeletal complications. Only 4.3% of patients were reported to be experiencing severe bone pain at the time of the study. Conclusions This cross-sectional, non-interventional study found high implementation of guideline-recommended BTA prescribing, good pain control and low incidence of skeletal-related events. Long-term BTA randomized controlled trials have the potential to further optimize routine care outcomes for patients.

Application of acetic acid to the cervix followed by colposcopic assessment with or without colposcopically directed biopsy is the standard test used to detect dysplastic lesions of the cervix. However, there is no evidence-based common standard defining how exactly to perform this test.To prospectively define the optimal timing for the colposcopic assessment of acetowhite lesions.Consecutive women referred to our colposcopy unit were recruited. Using a standardized colposcopy protocol, we recorded the most severe colposcopic lesion 1, 3, and 5 minutes after application of acetic acid (primary study end point). The time to first appearance of the most severe colposcopic lesion, highest staining intensity, and fading of the most severe colposcopic lesion were video documented (secondary study end points, assessed independently by 3 raters). Results were compared using parametric and nonparametric tests.A total of 300 women were included. After 1 minute, 290 of 300 patients (96.7%) were diagnosed with the most severe colposcopic lesion. This proportion did not improve after 3 minutes (290/300 [96.7%]) or after 5 minutes (233/264 [88.3%]). The proportion of minor and major changes continuously declined over time from 142 in 300 (47.3%; 1 minute) to 107 in 264 (40.5%; 5 minutes) and from 110 in 300 (36.7%) to 91 in 264 (34.5%), respectively. The median time until the first appearance of the most severe colposcopic lesion was 13.5 (interquartile range, 3-27.25) seconds and was significantly lower in high-grade squamous intraepithelial lesion (7 [interquartile range, 1-20] seconds) compared to low-grade squamous intraepithelial lesion (19 [interquartile range, 9-39.5] seconds; P.001). We observed fading of acetowhite lesions in 78% of cases, occurring at a median of 191 (interquartile range, 120-295) seconds after application of acetic acid. Fading started earlier in high-grade squamous intraepithelial lesion compared to low-grade squamous intraepithelial lesion (179.5 [interquartile range, 110- 253.25] versus 212.5 [interquartile range, 146.5-300]; P = .044). Overall, the net difference between colposcopic assessments at 3 minutes versus at 1 minute was 1 more high-grade squamous intraepithelial lesion and 1 less low-grade squamous intraepithelial lesion.It is reasonable to conclude that the best time to identify lesions is 1 minute after the application of acetic acid. Continued evaluation for up to 3 minutes may be considered reasonable for an optimal high-grade squamous intraepithelial lesion yield. However, fading of acetowhite lesions is common, especially in high-grade squamous intraepithelial lesions, and supports a recommendation of not prolonging colposcopy beyond 3 minutes.

Background: Extramammary Paget's disease of the vulva (EPDV) is a rare adenocarcinoma in situ of the vulvar skin and is often resected with involved margins due to its reticular growth pattern. Adjuvant treatment with the immunomodulator imiquimod may be suitable to avoid repeated and mutilating surgery. Case Presentation: We present the case of a 73-year-old woman with EPDV, initially treated with surgical resection and re-resection for involved margins. Final histology revealed Paget's disease of the left vulva with 8 cm in the largest diameter and again involved margins. Subsequently, topical therapy with imiquimod 5% cream twice weekly was applied for 3 months. Vulvoscopy and local biopsies confirmed complete remission (CR). Based on a literature search using PubMed and the Cochrane Central Register of Controlled Trials, 21 reports on the therapeutic efficacy of imiquimod in 70 women with EPDV have been published. Pooled rates of CR and partial remission were 71% (50/70) and 16% (11/70), respectively. There were 4 cases of disease progression under imiquimod and the therapy was generally well tolerated with mild to moderate local reactions in >50% of cases. Conclusion: EPDV is a rare genital neoplasia and may be successfully treated with the topical immunomodulator imiquimod. Specifically, adjuvant imiquimod is a feasible and efficacious treatment option for women with involved resection margins after surgery.