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Ovarian cancer (OC) accounts for approximately 4% of cancer deaths in women worldwide and is the deadliest gynecologic malignancy. High-grade serous ovarian cancer (HGSOC) is the most predominant ovarian cancer, in which BRCA1/2 gene mutation ranges from 3 to 27%. PARP inhibitors (PARPi) have shown promising results as a synthetically lethal therapeutic approach for BRCA mutant and recurrent OC in clinical use. However, emerging data indicate that BRCA-deficient cancers may be resistant to PARPi, and the mechanisms of this resistance remain elusive. We found that amplification of KRAS likely underlies PARPi resistance in BRCA2-deficient HGSOC. Our data suggest that PLK1 inhibition restores sensitivity to PARPi in HGSOC with KRAS amplification. The sequential combination of PLK1 inhibitor (PLK1i) and PARPi drastically reduces HGSOC cell survival and increases apoptosis. Furthermore, we were able to show that a sequential combination of PLK1i and PARPi enhanced the cellular apoptotic response to carboplatin-based chemotherapy in KRAS-amplified resistant HGSOC cells and 3D spheroids derived from recurrent ovarian cancer patients. Our results shed new light on the critical role of PLK1 in reversing PARPi resistance in KRAS-amplified HGSOC, and offer a new therapeutic strategy for this class of ovarian cancer patients where only limited options currently exist.

Ovarian cancer (OC) accounts for approximately 4% of cancer deaths in women worldwide and is the deadliest gynecologic malignancy. High-grade serous ovarian cancer (HGSOC) is the most predominant ovarian cancer, in which BRCA1/2 gene mutation ranges from 3 to 27%. PARP inhibitors (PARPi) have shown promising results as a synthetically lethal therapeutic approach for BRCA mutant and recurrent OC in clinical use. However, emerging data indicate that BRCA-deficient cancers may be resistant to PARPi, and the mechanisms of this resistance remain elusive. We found that amplification of KRAS likely underlies PARPi resistance in BRCA2-deficient HGSOC. Our data suggest that PLK1 inhibition restores sensitivity to PARPi in HGSOC with KRAS amplification. The sequential combination of PLK1 inhibitor (PLK1i) and PARPi drastically reduces HGSOC cell survival and increases apoptosis. Furthermore, we were able to show that a sequential combination of PLK1i and PARPi enhanced the cellular apoptotic response to carboplatin-based chemotherapy in KRAS-amplified resistant HGSOC cells and 3D spheroids derived from recurrent ovarian cancer patients. Our results shed new light on the critical role of PLK1 in reversing PARPi resistance in KRAS-amplified HGSOC, and offer a new therapeutic strategy for this class of ovarian cancer patients where only limited options currently exist.

The ideal management of early-stage cervical cancer has become the subject of a global controversy following the publication of a prospective study in 2018 that reported a worse oncologic outcome when comparing the minimally invasive approach to the laparotomy approach. The discussion involves both prospective and retrospective data and general and theoretical considerations. We wanted to look at the data available today and review the different opinions, offering an impartial assessment of the ongoing controversy.The available literature was reviewed, focusing on articles arguing for and against minimally invasive surgery in cervical cancer. We tried to avoid any fundamental bias, as is often evident in the available reviews on the subject. Literature both before and after the 2018 publication was taken into consideration.As is usual in discussions of concepts, the literature that is now available provides arguments for both sides of this challenging issue, depending on one's standpoint. Science-related writing is not immune to trends. There is a curious shift in opinion seen before and after 2018. One must question whether there was a prejudice in favor of minimally invasive surgery prior to the publication of the NEJM articles and a bias against it afterward.Whether further minimally invasive surgery for cervical cancer is invariable is tied to the more pressing question of how this surgery will have to be centralized in the future. Unless these questions are linked, no satisfactory solution can be found.

HIFU steht fur „high intensity focussed ultrasound“ und ist eine relativ neue Technologie, die als MRT(Magnetresonanztomographie)- oder als ultraschallgesteuertes HIFU angeboten wird. Wahrend der letzten Jahre sind vermehrt Arbeiten erschienen, die mogliche Optionen klarer definieren und den medizinischen Nutzen dieser neuen Methode objektiv nachweisen wollen. Inhalt der vorliegenden Publikation ist eine Darstellung der dominanten Techniken und der existierenden Literatur zum Stand der verfugbaren evidenzbasierten Medizin. Es soll herausgearbeitet werden, inwieweit Behauptungen zu Therapieerfolgen berechtigt sind und welche Entwicklungen in der Zukunft realistischerweise zu erwarten sind. Durchsicht der relevanten Datenbanken (PubMed, Medline, Embase) und der verfugbaren Industrieinformationen. HIFU ist eine komplexe Technologie, hinter der beachtliche technische Leistungen stehen. Der konkrete klinische Nutzen wird aktuell etabliert. Wie bei vielen neuen Technologien in der Fruhphase ist die Zukunft von HIFU weder garantiert noch komplett abzusehen. Aufgrund der einzigartigen Wirkweise konnte es sich um eine hochrelevante Zukunftstechnologie handeln. Bei der Kritik an aktuellen Insuffizienzen wird ubersehen, welche Schwierigkeiten ahnlich revolutionare Neuerungen, wie der diagnostische Ultraschall oder die Laparoskopie, uberwinden mussten, bevor sie aus der taglichen Routine nicht mehr wegzudenken waren. Die Frauenheilkunde sollte gegenuber dieser Zukunftstechnologie offen sein; es ware ein Fehler, ihr hohes innovatives Potenzial in Deutschland nicht weiter zu verfolgen.

Myomas, also known as fibroids, are a specific characteristic of the human species. No other primates develop fibroids. At a cellular level, myomas are benign hyperplastic lesions of uterine smooth muscle cells. There are interesting theoretical concepts that link the development of myomas in humans with the highly specific process of childbirth from an upright position and the resulting need for greatly increased “expulsive” forces during labor. Myomas might be the price our species pays for our bipedal and highly intelligent existence. Myomas affect, with some variability, all ethnic groups and approximately 50% of all women during their lifetime. While some remain asymptomatic, myomas can cause significant and sometimes life-threatening uterine bleeding, pain, infertility, and, in extreme cases, ureteral obstruction and death. Traditionally, over 50% of all hysterectomies were performed for fibroids, leading to a significant healthcare burden. In this article, we review the developments of the past 20 years with regard to multiple new treatment strategies that have evolved during this time.

Dargestellt wird die aktuelle Datenlage bezuglich epidemiologischer Beobachtungen und atiologischer Faktoren fur die unterschiedlichen Vulvamalignome. Das Wissen um die Epidemiologie, die Pathogenese und die atiologischen Faktoren des Vulvakarzinoms ist nicht nur relevant fur Praventionsstrategien, Fruherkennungsmasnahmen, die Implementierung von Screnningprogrammen und fur therapeutische Entscheidungen, sondern auch fur das postoperative Management im Sinne der Risikostratifizierung. Skizziert wird auch das beginnende Verstandnis der molekularbiologischen Pathways. Die weitere Forschung kann kunftig eine dezidiert neue Systematisierung der nosologischen Subentitaten initiieren, ferner moglicherweise auch innovative therapeutische Ansatze und Strategien ermoglichen.

Introduction Acute rejection following kidney transplantation (KTx) is still one of the challenging complications leading to chronic allograft failure. The aim of this study was to investigate the role of microdialysis (MD) in the early detection of acute graft rejection factor following KTx in porcine model. Methods Sixteen pigs were randomized after KTx into case (n = 8, without immunosuppressant) and control groups (n = 8, with immunosuppressant). The rejection diagnosis in our groups was confirmed by histopathological evidences as “acute borderline rejection”. Using MD, we monitored the interstitial concentrations of glucose, lactate, pyruvate, glutamate and glycerol in the transplanted grafts after reperfusion. Results In the early post-reperfusion phase the lactate level in our case group was significantly higher comparing to the control group and remained in higher levels until the end of monitoring. The lactate to pyruvate ratio showed a considerable increase in the case group during the post-reperfusion phase. The other metabolites (glucose, glycerol, glutamate) were nearly at the same levels at the end of our monitoring in both study groups. Conclusion The increase in lactate and lactate to pyruvate ratios seems to be an indicator for early detection of acute rejection after KTx. Therefore, MD as a minimally invasive measurement tool may help to identify the need to immunosuppression adjustment in the early KTx phase before the clinical manifestation of the rejection.

Summary Background/Objective Currently, due to lack of optimal donors, more marginal organs are transplanted. Therefore, there is a high interest to ameliorate preischemic organ preservation, especially for critical donor organs. In this regard, a new histidine-tryptophane ketoglutarate (HTK-N) solution has been designed and its protective efficacy was compared with the standard preservation solutions—University of Wisconsin solution and standard HTK or Custodiol (Bretschneider's solution). Methods Seventy-two landrace pigs were included into the study, as donors and recipients. The donor kidneys were perfused during explantation with cold University of Wisconsin solution ( n = 12), standard HTK ( n = 12), or HTK-N solutions ( n = 12), kept in the respective preservation solution at 4°C for 30 hours, implanted in the recipient pigs, and reperfused. The pigs survived in daily control for 7 days. The serum creatinine and blood urea nitrogen were assessed in pre- and postreperfusion phase on the 3 rd day and 7 th day posttransplantation. Additionally, tissue samples were taken to analyze the histopathological degree of tubular injury and regeneration before and after reperfusion. Results The three preservation groups were comparable in age, body weight, and hemodynamic parameters. According to statistical proof, they differed in none of the control parameters. Conclusion Although the new preservation HTK solution is in several points a well-thought-out modification of the standard HTK solution, its preservation efficacy, at least for kidney preservation in a pig model for 30 hours, seems to be comparable to the current used solutions. A real advantage, however, could be confirmed in clinical settings, where marginal organs may influence the clinical outcome.