Antitumor activity of rucaparib plus PLX038A in serous endometrial carcinoma.

Background: Serous endometrial cancer (SEC) is a genomically and morphologically distinct endometrial cancer (EC) subtype with a poor progression-free and overall survival. The development of novel therapies is needed to improve outcomes.

Methods: We used serous and serous-like EC patient-derived xenografts (PDXs) to test a novel drug combination in vitro and in vivo: rucaparib and pegylated SN-38 (PLX038A).

ECPPF stratification identifies occult high-risk subgroups in stage I, grade 1 or 2, ≤50 % invasive endometrial cancer: Candidates for adjuvant therapy.

Objective: To determine whether stratification with ECPPF (E2F1 + CCNA2 log2 expression and POLE, PPP2R1A, and FBXW7 variants) could identify occult cases of high-risk endometrial cancer (EC) in a traditionally low-risk cohort.

Methods: We identified 97 cases of clinicopathologic low-risk endometrioid EC (defined as stage I, grade 1 or 2, limited [≤50 %] myometrial invasion) from The Cancer Genome Atlas (TCGA). Twelve cases had POLE mutations (mu) and 15 had PPP2R1Amu or FBXW7mu.

Role of drug induced nuclear CTSL (nCTSL) in DNA damage response in cancer- therapeutic implications.

In our efforts to enhance sensitivity to PARP inhibitors, we identified clofarabine (CLF) as a potential therapy for drug-resistant ovarian cancer and nuclear trafficking of Cathepsin L (CTSL) as a treatment- responsive biomarker. Using PARP inhibitor-sensitive and -resistant OC cell lines, ex vivo cultures of patient-derived ovarian ascites (OVA), primary ovarian tumors, and xenografts (PDX), we found that CLF monotherapy induces nuclear CTSL (nCTSL) in CLF-responsive cells (CLF-r) and sensitizes them to PARP inhibitors olaparib and rucaparib. In CLF non-responsive cells (CLF-nr), a combination of CLF with olaparib is necessary for nCTSL trafficking and synergy.

Novel use of adjuvant proton beam therapy in patient with pelvic renal transplant diagnosed with stage IB3 cervical adenocarcinoma.

Cervical adenocarcinoma is the second most common histology of cervical cancer and treatment can involve surgery, radiotherapy, systemic therapy, and any combination of the three. Photon external beam radiation therapy and brachytherapy have been the mainstay of radiation treatment options for cervical cancer. Here, we report a case of a 41-year-old patient who had a prior renal transplant and was diagnosed with early-stage, intermediate-risk adenocarcinoma treated with modified radical hysterectomy plus adjuvant proton-beam therapy and vaginal brachytherapy.

Defining optimal perioperative analgesia in patients undergoing laparotomy for advanced gynecologic malignancy: A randomized controlled trial.

Background: Enhanced recovery after surgery (ERAS) pathways utilize multimodal analgesia. In pathways already utilizing incisional injection of liposomal bupivacaine (ILB), we assessed the benefit of adding intrathecal opioid analgesia (ITA).

Methods: In this randomized controlled non-inferiority trial in patients undergoing laparotomy for gynecologic malignancy, we allocated patients 1:1 to ILB alone versus ITA + ILB with 150 μg intrathecal hydromorphone.

Lost, mislabeled, and mishandled surgical and clinical pathology specimens: A systematic review of published literature.

Objectives: To perform a systematic review of published academic literature related to lost, mislabeled, and mishandled surgical and clinical pathology specimens during the preanalytical stage.

Methods: The authors used Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines to search PubMed, MEDLINE, Web of Science, and Scopus for relevant articles published from January 1, 1990, to May 1, 2023.

Results: The authors screened 1313 articles and identified 44 peer-reviewed, English-language articles published between 1990 and 2021 for inclusion in the final systematic review.

Cost-effectiveness analysis of margin-controlled surgery for vulvar Paget's disease.

Objectives: To determine the cost of two surgical treatment approaches for vulvar Paget's disease and model the cost-effectiveness considering differences in recurrence and reoperation over time.

Methods: We assessed cost-effectiveness between excision guided by Mohs micrographic surgery (MMS-E) and traditional wide local excision (WLE). We examined billing data from patients with vulvar Paget's disease who underwent MMS-E (cases, n = 24, 2018-2022) or WLE (controls, n = 64, 1990-2020).

Methylated DNA Markers for Sporadic Colorectal and Endometrial Cancer Are Strongly Associated with Lynch Syndrome Cancers.

Unlabelled: Lynch syndrome (LS) markedly increases risks of colorectal and endometrial cancers. Early detection biomarkers for LS cancers could reduce the needs for invasive screening and surgical prophylaxis.To validate a panel of methylated DNA markers (MDM) previously identified in sporadic colorectal cancer and endometrial cancer for discrimination of these cancers in LS.

Assessing the capacity of methylated DNA markers of cervical squamous cell carcinoma to discriminate oropharyngeal squamous cell carcinoma in human papillomavirus mediated disease.

Objective: Early identification of human papillomavirus associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) is challenging and novel biomarkers are needed. We hypothesized that a panel of methylated DNA markers (MDMs) found in HPV(+) cervical squamous cell carcinoma (CSCC) will have similar discrimination in HPV(+)OPSCC tissues.

Materials And Methods: Formalin-fixed, paraffin-embedded tissues were obtained from patients with primary HPV(+)OPSCC or HPV(+)CSCC; control tissues included normal oropharynx palatine tonsil (NOP) and cervix (NCS).

Sugammadex and urinary retention after hysterectomy: A propensity-matched cohort study.

Postoperative urinary retention (POUR) is a well-known complication after gynecologic surgery. Our objective was to investigate whether the choice of pharmacologic agent for reversing neuromuscular blockade at the end of a hysterectomy is a risk factor for POUR. Among adult patients undergoing hysterectomy with general anesthesia from 2012 to 2017, those who received aminosteroid nondepolarizing neuromuscular agents followed by pharmacologic reversal were identified, and electronic health records were reviewed.

Remotely Delivered Cancer Genetic Testing in the Making Genetic Testing Accessible (MAGENTA) Trial: A Randomized Clinical Trial.

Importance: Requiring personalized genetic counseling may introduce barriers to cancer risk assessment, but it is unknown whether omitting counseling could increase distress.

Objective: To assess whether omitting pretest and/or posttest genetic counseling would increase distress during remote testing.

Design, Setting, And Participants: Making Genetic Testing Accessible (MAGENTA) was a 4-arm, randomized noninferiority trial testing the effects of individualized pretest and/or posttest genetic counseling on participant distress 3 and 12 months posttest.

Mohs surgery for female genital Paget's disease: a prospective observational trial.

Background: Extramammary Paget's disease recurs often after traditional surgical excision. Margin-controlled surgery improves the recurrence rate for male genital disease but is less studied for female anatomy.

Objective: This study aimed to compare surgical and oncologic outcomes of margin-controlled surgery vs traditional surgical excision for female genital Paget's disease.

PG545 sensitizes ovarian cancer cells to PARP inhibitors through modulation of RAD51-DEK interaction.

PG545 (Pixatimod) is a highly sulfated small molecule known for its ability to inhibit heparanase and disrupt signaling mediated by heparan-binding-growth factors (HB-GF). Previous studies indicated that PG545 inhibits growth factor-mediated signaling in ovarian cancer (OC) to enhance response to chemotherapy. Here we investigated the previously unidentified mechanisms by which PG545 induces DNA damage in OC cells and found that PG545 induces DNA single- and double-strand breaks, reduces RAD51 expression in an autophagy-dependent manner and inhibits homologous recombination repair (HRR).

Incidence of venous thromboembolism in patients with advanced stage ovarian cancer undergoing neoadjuvant chemotherapy: Is it time for thromboprophylaxis?

Objectives: Our objectives were to determine the incidence, timing, and risk factors for venous thromboembolisms (VTEs) in patients with advanced stage epithelial ovarian cancer (EOC) who received neoadjuvant chemotherapy (NACT). We explored the utilization of direct-acting oral anticoagulants (DOACs) for VTE treatment.

Methods: This retrospective cohort study included patients with advanced stage EOC receiving NACT followed by interval cytoreductive surgery (ICS) at a single institution.

Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile.

Objective: To identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC.

Methods: We searched The Cancer Genome Atlas for DNA sequencing, RNA expression, and surveillance data regarding MSI-H/NSMP EC. We used a molecular classification system of and expression and sequence variations in , , or (ECPPF) to prognostically stratify MSI-H/NSMP ECs.

Caprini assessment utilization and impact on patient safety in gynecologic surgery.

Purpose: Postoperative venous thromboembolism (VTE) can potentially be associated with significant morbidity, mortality, and healthcare costs. The aim of this study was to determine the utilization of Caprini guideline indicated VTE in elective gynecologic surgery patients and its impact on postoperative VTE and bleeding complications.

Methods: This was a retrospective cohort study of elective gynecologic surgical procedures performed between January 1, 2016, and May 31, 2021.

ECPPF (E2F1, CCNA2, POLE, PPP2R1A, FBXW7) stratification: Profiling high-risk subtypes of histomorphologically low-risk and treatment-insensitive endometrioid endometrial cancer.

In endometrial cancer, occult high-risk subtypes (rooted in histomorphologically low-risk disease) with insensitivity to adjuvant therapies impede improvements in therapeutic efficacy. Therefore, we aimed to assess the ability of molecular high-risk (MHR) and low-risk (MLR) ECPPF (E2F1, CCNA2, POLE, PPP2R1A, FBXW7) stratification to profile recurrence in early, low-risk endometrioid endometrial cancer (EEC) and insensitivity to platinum-based chemotherapy or radiotherapy (or both) in high-risk EEC. Using The Cancer Genome Atlas endometrial cancer database, we identified 192 EEC cases with available DNA sequencing and RNA expression data.

Using Social Media to Facilitate Communication About Women's Testing: Tool Validation Study.

Background: Strong participant recruitment practices are critical to public health research but are difficult to achieve. Traditional recruitment practices are often time consuming, costly, and fail to adequately target difficult-to-reach populations. Social media platforms such as Facebook are well-positioned to address this area of need, enabling researchers to leverage existing social networks and deliver targeted information.

NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.