Successful pregnancy with in vitro fertilization after vaginal radical trachelectomy and pelvic lymphadenectomy in stage IB1 cervical cancer.

OBJECTIVE: To present a case of successful pregnancy after undergoing vaginal radical trachelectomy (VRT) and pelvic lymph node dissection (PLND) for early-stage cervical cancer. CASE REPORT: A 37-year-old female patient has been diagnosed with stage IB1 cervical cancer and underwent VRT and PLND. Two years after the surgery, the patient successfully conceived and delivered a healthy baby through a cesarean section. CONCLUSION: This case report demonstrates that pregnancy after VRT and PLND for stage IB1 cervical cancer is possible and can result in a successful outcome. This report provides valuable information for patients and physicians who are considering these surgical options.

Emergent cesarean section in a preterm pregnant woman with severe COVID-19 pneumonia in Taiwan: A case report.

OBJECTIVE: The pandemic Coronavirus Disease 2019 (COVID-19) is a global public health crisis. Many maternity units worldwide are currently establishing the management protocols for these patients. CASE REPORT: We report the first critically ill pregnant woman with COVID-19-induced respiratory failure undergoing emergent caesarean delivery at 32 weeks of gestation, in the setting of a positive pressure operating room (OR) with negative pressure anteroom in Taiwan. CONCLUSION: Multidisciplinary planning and collaboration are necessary to achieve satisfactory clinical outcomes in pregnancies with critical COVID-19 pneumonia. The combinations of comprehensive evaluation, timely treatment as well as establishment of rigorous protocol and safe environment for the emergent delivery are important.

The Molecular Mechanisms of Actions, Effects, and Clinical Implications of PARP Inhibitors in Epithelial Ovarian Cancers: A Systematic Review.

Ovarian cancer is the most lethal gynecologic malignancy in the United States. Some patients affected by ovarian cancers often present genome instability with one or more of the defects in DNA repair pathways, particularly in homologous recombination (HR), which is strictly linked to mutations in breast cancer susceptibility gene 1 (BRCA 1) or breast cancer susceptibility gene 2 (BRCA 2). The treatment of ovarian cancer remains a challenge, and the majority of patients with advanced-stage ovarian cancers experience relapse and require additional treatment despite initial therapy, including optimal cytoreductive surgery (CRS) and platinum-based chemotherapy. Targeted therapy at DNA repair genes has become a unique strategy to combat homologous recombination-deficient (HRD) cancers in recent years. Poly (ADP-ribose) polymerase (PARP), a family of proteins, plays an important role in DNA damage repair, genome stability, and apoptosis of cancer cells, especially in HRD cancers. PARP inhibitors (PARPi) have been reported to be highly effective and low-toxicity drugs that will tremendously benefit patients with HRD (i.e., BRCA 1/2 mutated) epithelial ovarian cancer (EOC) by blocking the DNA repair pathways and inducing apoptosis of cancer cells. PARP inhibitors compete with NAD+ at the catalytic domain (CAT) of PARP to block PARP catalytic activity and the formation of PAR polymers. These effects compromise the cellular ability to overcome DNA SSB damage. The process of HR, an essential error-free pathway to repair DNA DSBs during cell replication, will be blocked in the condition of BRCA 1/2 mutations. The PARP-associated HR pathway can also be partially interrupted by using PARP inhibitors. Grossly, PARP inhibitors have demonstrated some therapeutic benefits in many randomized phase II and III trials when combined with the standard CRS for advanced EOCs. However, similar to other chemotherapy agents, PARP inhibitors have different clinical indications and toxicity profiles and also face drug resistance, which has become a major challenge. In high-grade epithelial ovarian cancers, the cancer cells under hypoxia- or drug-induced stress have the capacity to become polyploidy giant cancer cells (PGCCs), which can survive the attack of chemotherapeutic agents and start endoreplication. These stem-like, self-renewing PGCCs generate mutations to alter the expression/function of kinases, p53, and stem cell markers, and diploid daughter cells can exhibit drug resistance and facilitate tumor growth and metastasis. In this review, we discuss the underlying molecular mechanisms of PARP inhibitors and the results from the clinical studies that investigated the effects of the FDA-approved PARP inhibitors olaparib, rucaparib, and niraparib. We also review the current research progress on PARP inhibitors, their safety, and their combined usage with antiangiogenic agents. Nevertheless, many unknown aspects of PARP inhibitors, including detailed mechanisms of actions, along with the effectiveness and safety of the treatment of EOCs, warrant further investigation.