Prevention, Screening, Treatment and Follow-Up of Gynecological Cancers: State of Art and Future Perspectives

Objective: This study aims to analyze the available data on prevention and early diagnosis in gynecological cancers. Mechanism: A comprehensive search was performed in the PubMed (MEDLINE), EMBASE, SCOPUS and Web of Science databases. Findings in Brief: To date the prevention programmes of all degrees exist exclusively for cervical cancer. Human Papilloma Virus (HPV) vaccination prevents from infection and development of precancerous lesions and contributes significantly to the deflection of the incidence of cervical cancer. Screening for HPV-related lesions is worldwide performed by cervical smear (Pap-test) and HPV test. Finally, tertiary prevention is aimed at the treatment of previously diagnosticated lesions with the aid of surgery, chemotherapy, radiotherapy and immunotherapy. Unfortunately, to date the prevention programmes of other gynecological tumors have not reached a good performance; indeed, the primum movens that leads to the development of such neoplasms has not been identified yet. Actually, no screening programs for the early diagnosis of endometrial cancer are available, however, it is recommended the adoption of a healthy lifestyle and a balanced diet. Diagnostic biomarkers would be helpful for screening asymptomatic high-risk women, but histopatological examinations remain the gold standard for diagnosis of endometrial cancer. Similarly, there are no screening tests for the diagnosis of ovarian cancer. In recent years many steps forward have been made in this field and new perspectives have been presented, however, additional investigation is needed to optimize the duration and timing of treatment, examine its cost-effectiveness, and identify potential tumor or host biologic factors predictive of the efficacy and adverse events. Finally, there are no primary and secondary prevention for vulvar cancer so patients should be invited to self-examination and pay attention to the presence of symptoms. Conclusions: Are the available screening programs for the diagnosis of gynecological carcinomas sufficient? The prevention and the diagnosis of precancerous lesions is the goal to be achieved for all gynecological cancers in order to improve patient outcomes, reduce the costs for managing the disease and prolonged follow up

Vulvar lipoma: rare case, rare location

Background. Vulvar lipomas are very rare pathologies: indeed, only few cases are reported in the literature. Case presentation. We reported clinical, diagnostic and therapeutical choices of a 44-year aged patient with a rare abnormally sized vulvar lipoma. A Diamond-shaped skin incision was performed and the neoformation was removed without capsule lesions. A vaginal plastic skin-reducing was performed to reduce redundant tissue. The deep planes of the lesion have been reconstructed to avoid leakage. Conclusions. This kind of lipomas can be potentially diagnosed through clinical examination because of their specific characteristics. However, imaging is advisable to differentiate benign neoplasm from malignant one. Different approaches can be achieved for lipomas based on the size of lump, patient’s feelings and necessities and the operation goals; however, the complete surgical excision with the removal of capsules to prevent recurrence remains the treatment of choice for vulvar lipomas. Different surgical approaches aim to achieve better esthetical results, less scarring, and less colour discordance of the connected tissues post-surgery. Surgery is the gold standard for treatment of vulvar lesions. Currently, there is no evidence of long-term follow-up in the literature. We recommend an adequate counselling with the patient to understand their needs and encouraging them to seek medical advice and to tailor the treatment of such lesions

Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer

To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer

The role of immunotherapy in advanced and recurrent MMR deficient and proficient endometrial carcinoma

Endometrial cancer is the most common gynecological disease in developed countries. Although it is considered an indolent disease, advanced and recurrent endometrial carcinomas are characterized by poor prognosis. In the metastatic setting, after the failure of first-line platinum-based chemotherapy, patients have limited therapeutic options. However, endometrial cancer should not be considered as a single entity but as a group of heterogeneous diseases with specific genomic, molecular, and biological features by suggested the analysis of The Cancer Genome Atlas (TCGA). Accumulating data highlighted the effectiveness and safety of the adoption of immune checkpoint inhibitors (ICIs) for several types of solid tumors. In particular, immunotherapy showed promising results in MSI-H/dMMR solid tumors. Endometrial cancer is not an exception. Endometrial cancer has the highest prevalence of MSI across human cancer types, and approximately 30% of primary endometrial cancers are MSI-H/dMMR and 13% to 30% of recurrent endometrial cancers are MSI-H/dMMR. The preliminary results of the KEYNOTE-158, the Australian NCT03015129 and the GARNET trial strongly supported the adoption of ICIs as monotherapy in patients with advanced or recurrent endometrial cancer, after the failure of first-line treatments. Unfortunately, those impressive results are not achieved in patients with MMR proficient disease. Hence, other combinations were tested. In particular, the adoption of ICIs plus tyrosine kinase inhibitors (TKI) showed very compelling results. Recently, the updated results of the KEYNOTE-775 showed that pembrolizumab plus lenvatinib led to significantly longer progression-free and overall survival than chemotherapy among patients with advanced endometrial cancer, irrespective of MMR status. After EMA approval, pembrolizumab plus lenvatinib represents the new standard second-line treatment in endometrial cancer patients, regardless MMR status. Further studies are investigating the role of ICIs and TKIs in the first line and are testing new combinations (e.g. ICIs plus PARP inhibitors)

PARP Inhibitors in Newly Diagnosed and Recurrent Ovarian Cancer

Ovarian cancer is the most lethal gynecologic malignancy, characterized by a high death-to-incidence ratio. Platinum-based chemotherapy is the mainstay of treatment for newly diagnosed and platinum-sensitive recurrent ovarian cancer. Poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) have been incorporated into the treatment strategy for ovarian cancer. PARP inhibitors showed particular benefit for patients harboring defects in DNA repair pathways. Accumulating evidence showed that PARP inhibitors provide a benefit in newly diagnosed advanced ovarian cancer, even in the absence of BRCA mutation, as reported in the PRIMA, PRIME, and ATHENA-mono trials. Interestingly, the PAOLA-1 study provides another important finding, supporting the adoption of olaparib plus bevacizumab in patients with homologous recombination deficiency. Although those results are exciting, several patients develop resistance to PARP inhibitors. Hence, new combinations are under investigation to identify new treatment strategies to overcome this resistance. Currently, researchers are focused on the possibility to adopt PARP inhibitors even in the setting of platinum-resistant disease. The present critical review aims to report the current landscape and further perspective for strengthening PARP inhibitors' effectiveness in newly diagnosed and recurrent ovarian cancer

Vulvodynia. A practical guide in treatment strategies

Vulvodynia is a debilitating condition characterized by chronic vulvar pain, with a detrimental impact on the patient's overall quality of life. Its etiology is multifactorial, but still in the process of being clearly outlined. Vulvodynia is not a single entity. It is a heterogeneous condition characterized by multiple triggers, making it challenging to define a reference standard for its treatment. In this manuscript we selected all articles including the following key criteria: "vulvodynia". The primary outcomes observed included the resolution of chronic pelvic pain, dyspareunia and sexual satisfaction, psychological well-being, and overall quality of life. Most pharmacologic treatments require further evidence to be recommended. On the other hand, non-pharmacologic approaches such as psychotherapy, physical therapy, and surgery have received stronger support. This review summarizes pros and cons of adopting available treatments. Multimodal approaches should be introduced to improve patient outcomes. Further investigations are warranted to improve patients' quality of life

Staatsfonds für eine effiziente Altersvorsorge: Welche innovativen Lösungen sind möglich?

Millionen Menschen in Deutschland sind von Altersarmut bedroht. Und das Risiko, von Altersarmut betroffen zu sein, wird in den nächsten Jahren vor allem durch den bevorstehenden Eintritt der Babyboomer-Generation in den Ruhestand noch steigen. Die umlagefinanzierte gesetzliche Rentenversicherung stößt an ihre Grenzen. Und die private kapitalgedeckte Altersvorsorge ist in Deutschland bei weitem nicht in dem Maße verbreitet, um die entstehende Rentenlücke schließen zu können. Innovative Lösungen sind gesucht. Clemens Fuest, Christa Hainz, Volker Meier, ifo Institut, und Martin Werding, Ruhr-Universität Bochum, entwickeln das Konzept des »Deutschen Bürgerfonds«, der die private Altersvorsorge und die Vermögensbildung der privaten Haushalte stärken soll. Damit könnte die Versorgungslücke bei Geringverdienern verringert werden. Die hervorragende Bonität der Bundesrepublik Deutschland als Schuldner ermögliche es, Kredite günstig aufzunehmen und bei einer Reinvestition eine erhebliche Renditedifferenz zu erzielen. Simulationen zeigen: Lege der Staat ab heute 0,5% des BIP pro Jahr für alle Erwerbsfähigen an, finanziert durch langsameren Staatsschuldenabbau, ergäbe sich nach 50 Jahren bei einer durchschnittlichen Renditedifferenz von 2 Prozentpunkten ein Ertrag von gut 16 000 Euro pro Kopf, der mit dem Erreichen von 67 Jahren ausgezahlt werden könnte. Bei einer Zinsdifferenz von 3 Prozentpunkten kämen bereits rund 30 000 Euro zusammen. Die Verwaltung des »Deutschen Bürgerfonds« sollte unabhängig sein und beispielsweise durch die Bundesbank erfolgen. Giacomo Corneo, FU Berlin, schlägt die Gründung einen Staatsfonds durch die Bundesregierung vor, dessen Anfangsvermögen durch die Ausgabe von zweckgebundenen Bundesanleihen finanziert wird. Der Staatsfonds hätte die Aufgabe, das erhaltene Kapital so zu investieren, dass seine risikoangepasste Rendite langfristig maximiert würde. Die erzielte Rendite wird in Form einer Altersdividende an die Bevölkerung im Alter von über 67 Jahre ausgezahlt. Durch diese Altersdividende würde das Armutsrisiko drastisch vermindert, und die verfügbaren Einkommen der Mittelschicht würden stabilisiert. Da der Fonds überwiegend in risikobehaftete Anlagen, hauptsächlich in den globalen Aktienmarkt, investieren soll, käme es zu einer diversifizierten gemeinsamen Beteiligung aller Haushalte am globalen Aktienmarkt und zu einer Pareto-Verbesserung. Hans Peter Grüner, Universität Mannheim, hält die Einrichtung eines schuldenfinanzierten Staatsfonds, dessen mutmaßliche Zinsdifferenzgewinne zur Finanzierung eines vergrößerten Staatsbudgets eingesetzt werden sollen, für einen »verheerenden Fehler«. Zum einen unterliegen die Erträge auf einem Aktienmarkt großen Schwankungen und können positiv oder negativ sein. Zum anderen verschlechtert ein riskanter Staatsfonds die Bonität des Staates. Und schließlich werden die Begehrlichkeiten verschiedener Interessengruppen und Parteien, die entsprechenden Mittel nach eigenem Gusto zu verwalten, zu einem Wertverlust des Staatsfonds führen. Dennis Huchzermeier und Bert Rürup, Handelsblatt Research Institute, sehen in dem Vorschlag eines Bürgerfonds kein adäquates Instrument, der zukünftig steigenden Altersarmut entgegenzuwirken. Zum einen seien die aus diesem Fonds zugeteilten Summen zu gering. Zum anderen würde es sich um eine unzulängliche »End-of-the-pipe«-Maßnahme handeln; denn keine der Ursachen für Altersarmut wie Langzeitarbeitslosigkeit oder unter­brochene Erwerbsbiographien werden beseitigt oder auch nur verringert. Eine bessere Alternative sei ein von einer staatsfernen Non-Profit-Organisation verwaltetes System von individuellen Vorsorgekonten. Dies könnte eine neu zu gründende Stiftung des öffentlichen Rechts sein, die die Spareinlagen nicht selbst managen, sondern externe Asset-Managern und Versicherer betrauen würde, die für die Vermögensanlage und die spätere Ver­rentung des angesparten Kapitals zuständig wären. Die Inanspruchnahme privater, kapitalgedeckter Altersvorsorgemöglichkeiten bleibt weit hinter den Erwartungen zurück. Dafür sind nach der Analyse von Andreas Knabe und Joachim Weimann, Universität Magdeburg, zwei Gründe verantwortlich. Zum einen neigen viele Menschen dazu, im jeweiligen Status quo zu verharren. Bei der Altersvorsorge bedeute das, dass sie nur über die gesetzliche, aber nicht über eine zusätzliche private Alters­vorsorge verfügen. Zum anderen leide der Markt für private Altersvorsorge unter zu geringem Wettbewerb. Mit ihrem Konzept der »Deutschlandrente« soll mit einem staatlich organisierten Investmentfonds ein transparentes und kostengünstiges Angebot geschaffen werden, das im Wettbewerb zu bestehenden Anbietern steht. Und diese zusätzliche Altersvorsorge wird von einer Zustimmungs- zu einer Widerspruchslösung umgestellt: Solange man nicht aktiv widerspricht, wird jeder sozialversicherungspflichtig Beschäftigte in die zusätzliche kapitalgedeckte Altersvorsorge einbezogen. Christine Bortenlänger und Donato Di Dio, Deutsches Aktieninstitut, sind der Ansicht, dass es effizientere Lösungen als Staatsfonds gibt, um den Bürgern ein gutes Auskommen im Alter zu sichern. Die Beispiele Australiens, Schwedens, Großbritanniens und Kanadas, die in der Altersvorsorge auf den Kapitalmarkt setzen, zeigten dies: Die Modelle bewährten sich im Wettbewerb, zudem könnten private Anbieter ihren Kunden ein vielfältiges, maßgeschneidertes Angebot anbieten. Auch Deutschland sollte mehr Aktien in der Altersvorsorge nutzen und so den Bürgerinnen und Bürgern eine bessere Rente ermöglichen

Role of Genomic and Molecular Biology in the Modulation of the Treatment of Endometrial Cancer: Narrative Review and Perspectives

Endometrial cancer (EC) is one of the most common gynecological malignancies in Western countries. Traditionally, loco-reginal dissemination and histological characteristics are the main prognostic factors. Nowadays, molecular and genomic profiling showed exciting results in terms of prognostication. According to the data provided by The Cancer Genome Atlas and other studies, molecular and genomic profiling might be useful in identifying patients al low, intermediate, and high risk of recurrence. However, data regarding the therapeutic value are scant. Several prospective studies are ongoing to identify the most appropriate adjuvant strategy in EC patients, especially for those with positive nodes and low volume disease. The molecular classification has offered the possibility to improve the risk stratification and management of EC. The aim of this review is to focus on the evolution of molecular classification in EC and its impact on the research approach and on clinical management. Molecular and genomic profiling might be useful to tailor the most appropriate adjuvant strategies in apparent early-stage EC

Spotlight on Compounded Bioidentical Hormones

Background: The role of hormonal replacement therapy in menopause is under debate. The premature closure of the Women's Health Initiative (WHI) study in 2002 is still a source of concern among treating physicians. Objectives: The interest in alternatives to conventional hormone therapy has significantly increased. The adoption of personalized steroid hormone galenic preparations, formulated by compounding pharmacies, has recently spread. Methods: In June 2023, an extensive literature search was conducted by different authors to identify relevant studies in various databases (MEDLINE, Embase, Pubmed, and Cochrane). The studies that met the inclusion and exclusion criteria were further analyzed, and relevant data were extracted and analyzed for each paper. Any discrepancies between the investigators were resolved through a consensus approach. Outcomes: The primary outcomes observed included the clinical utility of CBHT. This study reviewed the current evidence on the utility of compounded bioidentical hormones, concluding that improving knowledge and awareness of bioidentical hormones is necessary to consider their use in clinical practice. Conclusion and outlook: These formulations might provide effective options to best tailor therapies to each patient