First reported case of Robinsoniella peoriensis pyometra and bloodstream infection: A case report and review of the literature.

We report on a 47-year-old woman with jejunal adenocarcinoma and concurrent endometrial cancer, admitted with sepsis. Uterine fluid and blood cultures were positive for Robinsoniella peoriensis. This is the first case report of Robinsoniella peoriensis in Canada. We encourage clinicians to publish their experience treating gynecologic infections caused by Robinsoniella peoriensis. Failure to recognize this pathogen as causative for pyometra, may result in insufficient antimicrobial treatment, and death.

Hormone maintenance therapy for women with low-grade serous ovarian cancer in the front-line setting: A systematic review.

OBJECTIVE: Low-grade serous ovarian cancer (LGSOC) is a rare form of ovarian cancer that accounts for 5-10% of epithelial ovarian cancers. LGSOCs are difficult to treat as they respond poorly to traditional chemotherapy treatments. This systematic review aims to appraise the literature describing the efficacy of hormone maintenance therapy (HMT) in patients with LGSOC given after cytoreductive surgery. METHODS: Medline, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were searched from inception to November 2020. No language restrictions were applied. Publications describing HMT in the primary setting following cytoreductive surgery with or without chemotherapy in women with LGSOC were included. Publications describing HMT in recurrence, non-LGSOC carcinomas, and in-vitro or animal studies were excluded along with case reports, case series, and conference proceedings. We summarized oncologic outcomes, HMT used, and hormone receptor status where reported. Studies were assessed for risk of bias and quality of evidence. RESULTS: The literature search identified 14,799 records. Four cohort studies met eligibility criteria. A total of 558 patients were included, of which 127 were treated with HMT. There was significant heterogeneity between studies demonstrated by differences in HMT regimens used, dosing, and study population, leading to various outcomes following treatment with HMT. CONCLUSIONS: Treatment of LGSOC remains a challenge. One retrospective study demonstrated improved progression-free survival following HMT for LGSOC, while two others failed to show significant improvements. However, there is limited data available in the literature which restricts the generalizability of these results. Therefore, well-designed, prospective, and randomized trials are needed to confirm the benefit of HMT in patients with this rare subgroup of ovarian cancer.

Does Radical Hysterectomy for Clinically Apparent Stage II Endometrial Cancer Affect Risk of Local Recurrence?

OBJECTIVE: Compare recurrence-free survival (RFS) and morbidity between radical hysterectomy (RH) and simple hysterectomy (SH) for clinically diagnosed stage II endometrial cancer. METHODS: A multicentre, retrospective study, from 2000 to 2015, involving patients with endometrial cancer with cervical involvement preoperatively and stromal invasion on final pathology. Wilcoxon rank-sum test, Fisher exact test, Kaplan-Meier survival functions, and Cox proportional hazards models were used for analysis. RESULTS: Ninety of 1613 patients had clinical stage II endometrial cancer; 57 underwent RH and 33 underwent SH, with no difference in adjuvant treatment or morbidity. About half of patients (51%) had pathologic stage III-IV disease. Mean follow-up was 3.3 and 3.8 years for SH and RH, respectively. Thirty-three percent of patients with RH and SH experienced a recurrence. Most recurrences were distant: 90% with SH and 79% with RH. There was no difference in RFS between groups (2-year: SH 65% vs. RH 75%; 5-year: SH 54% vs. RH 63%; P = 0.72). Controlling for stage, adjuvant treatment, and margin status, RH was not associated with RFS (HR 0.62; 95% CI 0.28-1.35). Among 44 patients with pathologic stage II disease, 7 had a recurrence (4 SH and 3 RH); 6 of 7 had distant recurrences. CONCLUSIONS: Fifty-one percent of patients with clinical stage II endometrial cancer had advanced disease on final pathology, highlighting the importance of surgical staging. RH was not associated with RFS or reduced morbidity. Most recurrences were distant. Although RH could be performed to achieve negative surgical margins, SH may be sufficient for central, small tumours given the high risk of advanced disease and distant recurrence. Research efforts should further elucidate the ideal management of these patients.

Uptake of sentinel lymph node procedures in women with vulvar cancer over time in a population based study.

OBJECTIVES: To evaluate trends in uptake of sentinel lymph node (SLN) procedures over time and associated factors in women with vulvar cancer. METHODS: A retrospective population-based cohort study identified women with invasive squamous cell carcinoma (SCC) of the vulva using health administrative data for the province of Ontario, Canada, between 2008 and 2016. Patients who underwent SLN procedures were compared to those who had groin node dissection (GND). Multivariable analysis was used to identify factors associated with SLN procedures. RESULTS: 1385 patients with SCC of the vulva were identified; 1079 had a surgical procedure. Only those with groin node assessment were included in the study cohort (n = 732, 68%). SLN procedures were done in 52%. When comparing SLN versus GND, the rate of SLNs was significantly different by year of diagnosis (P < 0.001), associated comorbidity (P < 0.001) and institution (P < 0.0001). The rates of SLNs by institution with gynecologic oncologist were variable and ranged from 32% to 79% among 9 centers. There were no differences in age, income quintile, and urban/rural residence. The proportion of SLN procedures increased from 30.1% (CI 18.9-45.6) in 2008 to 65.2% (CI 36.5-107.6) in 2016. On multivariate analysis, factors significantly associated with SLN procedures were more recent year of diagnosis (OR 7.9, CI 2.7-23.5) associated comorbidities (OR 2.7, CI 1.5-5.0) and institution (Site 5, OR 19.6 [CI 3.6-108.3] and Site 6, [OR 6, CI 1.1-33.4]). CONCLUSIONS: The proportion of SLN procedures in women with vulvar cancer has increased over time, but uptake is not uniform across institutions. Barriers to uptake should be explored.

Early Cervical Cancer: Current Dilemmas of Staging and Surgery.

PURPOSE OF REVIEW: Advances in cervical cancer screening and treatment have resulted in high cure rates in developed countries for early-stage disease. Current research focuses on minimizing morbidity and maximizing quality of life. RECENT FINDINGS: Imaging has been disappointing in identifying small volume metastases. Sentinel lymph node biopsy represents a significant advantage with high sensitivity, low false negative rates, reduced morbidity, and equivalent survival in recent studies compared to pelvic lymphadenectomy. Non-radical surgical options are currently being investigated for early cervical cancer in a number of large prospective studies in patients at low risk for metastases. Evidence suggests that sentinel lymph node biopsy and non-radical surgery are safe approaches for the staging and management of early cervical cancer in appropriately selected patients with the potential to significantly reduce treatment-related morbidity.

Dacomitinib (PF-00299804), a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor, demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro.

Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that carries an extremely poor prognosis. Up to 35 % of USC may overexpress the epidermal growth factor receptor-2 (HER2/neu) at strong (i.e., 3+) level by immunohistochemistry (IHC) or harbor HER2/neu gene amplification by fluorescence in situ hybridization (FISH). In this study, we assessed the sensitivity of a panel of USC cell lines with and without HER2/neu gene amplification to dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor tyrosine kinase inhibitor. Eight primary cell lines (i.e., four harboring HER2/neu gene amplification by FISH and four FISH- cell lines), all demonstrating similar in vitro growth rates, were evaluated in viability/proliferation assays. The effect of dacomitinib on cell growth, cell cycle distribution, and signaling was determined using flow cytometry-based assays. Dacomitinib caused a significantly stronger growth inhibition in HER2/neu FISH+ USC cell lines when compared to FISH- USC (dacomitinib half maximal inhibitory concentration (IC50) mean ± SEM = 0.02803 ± 0.003355 µM in FISH+ versus 1.498 ± 0.2209 µM in FISH- tumors, P < 0.0001). Dacomitinib growth inhibition was associated with a significant and dose-dependent decline in phosphorylated HER2/neu and S6 transcription factor and a dose-dependent and time-dependent cell cycle arrest in G0/G1 in FISH+ USC. Dacomitinib is remarkably effective against chemotherapy-resistant HER2/neu gene-amplified USC. Clinical studies with dacomitinib in HER2/neu FISH+ USC patients resistant to standard salvage chemotherapy are warranted.

Treatment of Recurrent Low-grade Serous Ovarian Cancer With MEK Inhibitors: A Systematic Review.

OBJECTIVE: Low-grade serous ovarian cancer (LGSC) represents 5% of all epithelial ovarian cancers. They are characterized by indolent growth and KRAS and BRAF mutations, differing from high-grade serous ovarian cancer both clinically and molecularly. LGSC has low response rates to traditional systemic therapies, including chemotherapy and hormonal therapy. The objective of this systematic review was to appraise the literature describing the efficacy of MEK inhibitors in the treatment of LGSC. METHODS: A comprehensive search was conducted of the following databases: Medline ALL, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Sciences, ClinicalTrials.gov, International Clinical Trials Registry Platform (ICFRP), and International Standard Randomized Controlled Trials Number (ISRCTN) Registry. All studies investigating MEKi in the treatment of LGSC in the adjuvant or recurrent setting for patients 18 years of age or older were included. All titles/abstracts were then screened by 2 independent reviewers (A.K. and C.C.). The full-text articles were then screened. All disagreements were resolved by a third independent reviewer (T.Z.). Two independent reviewers (A.K. and C.C.) extracted data from the studies deemed eligible for final review. RESULTS: A total of 2108 studies were identified in the initial search. Of these, a total of 4 studies met the eligibility criteria for systematic review. In these studies, 416 patients were treated with an MEKi alone. All patients included in the studies were being treated for LGSC in the recurrent setting. Varied results and efficacy of the MEKi were reported in each study. CONCLUSIONS: The results highlighted in this systematic review demonstrate varied responses to MEKi for recurrent LGSC. Further research is needed in this field comparing the efficacy to current therapies, as well as to further evaluate the safety and toxicity profile with long-term use of MEKi.

Bevacizumab Treatment for Low-Grade Serous Ovarian Cancer: A Systematic Review.

Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings.

Canadian Guideline on the Management of a Positive Human Papillomavirus Test and Guidance for Specific Populations.

The purpose of this paper is to provide evidence-based guidance on the management of a positive human papilloma virus (HPV) test and to provide guidance around screening and HPV testing for specific patient populations. The guideline was developed by a working group in collaboration with the Gynecologic Oncology Society of Canada (GOC), Society of Colposcopists of Canada (SCC), and the Canadian Partnership Against Cancer. The literature informing these guidelines was obtained through a systematic review of relevant literature by a multi-step search process led by an information specialist. The literature was reviewed up to July 2021 with manual searches of relevant national guidelines and more recent publications. The quality of the evidence and strength of recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The intended users of this guideline include primary care providers, gynecologists, colposcopists, screening programs, and healthcare facilities. The implementation of the recommendations will ensure an optimum implementation of HPV testing with a focus on the management of positive results. Recommendations for appropriate care for underserved and marginalized groups are made.

Innovations in the Management of Vaginal Cancer.

Primary vaginal cancer is a rare gynecologic malignancy. Given the rarity of the disease, standardized approaches to management are limited, and a great variety of therapeutic conditions are endorsed. This paper reviews advances in surgical approaches, radiation, chemoradiation, and immunotherapy. Advances in surgical management including the increasing use of laparoscopic and endoscopic approaches, as well as the novel techniques in vaginal reconstruction, are reviewed. Concurrent chemoradiation remains a mainstay of treatment for vaginal cancer and has improved local control of disease and overall survival. Additionally, with metastatic disease or situations where toxicity from CCRT is unacceptable, systemic therapies including immunotherapy approaches are reviewed.

Identifying Borderline Ovarian Tumor Recurrence Using Routine Ultrasound Follow-Up.

Borderline ovarian tumors (BOTs) are non-invasive tumors frequently diagnosed in young patients. Surgical removal of the uterus, fallopian tubes, ovaries, and omentum is considered definitive management, however fertility-sparing approach is a recognized option. Surveillance is important due to known recurrence, but there is controversy over the effectiveness of follow-up modalities. The objective is to determine the efficacy of ultrasound screening in identifying tumor recurrence. This retrospective chart review evaluated all patients consulted and/or treated surgically at our institution from January 2015 to June 2020 diagnosed with BOT. Patients were excluded if concurrently diagnosed with another gynecologic malignancy, did not have yearly ultrasound follow-up, or were lost to follow-up. This study included 56 patients, 17 of whom underwent fertility preserving surgery. The overall rate of recurrence was 10.7%; with recurrence rates of 23.5% for the fertility preserving surgery population and 5.1% for the definitive surgery population. Ultrasound first identified 5 of the 6 (83.3%) recurrences. Overall time to recurrence was 51.5 months. In conclusion, recurrences were identified on routine ultrasound screening prior to symptom onset or detection via physical exam in 83.3% of cases. While the best modality of follow-up remains controversial, this review provides evidence supporting the use of routine ultrasound follow-up for early detection of BOT recurrence.

Second harmonic generation microscopy to investigate collagen configuration: a pericarditis case study.

We have used second-harmonic-generation (SHG) to image collagen fibers in pericardial tissue removed from a patient with constrictive pericarditis and compared this to healthy pericardium. SHG imaging allowed for the visualization of collagen fibers without the need for staining or pretreatment. Images were compared to stained histology slides. Collagen fibers in SHG and histology images displayed the same structure and morphology. The mature collagen of the parietal pericardium was easily distinguishable from the new collagen accumulation due to the pericarditis. SHG imaging can provide a convenient and valuable architectural profile of collagen organization.

A comparison of mechanical properties of materials used in aortic arch reconstruction.

BACKGROUND: Differences in the mechanical properties of aortic tissues and replacement materials can have unwanted hemodynamic effects leading to graft failure. The aim of this experimental study was to compare the mechanical properties of different graft-patch materials used in aortic arch reconstruction with those of healthy and dilated human ascending aortas (AAs). METHODS: Four square samples were taken from 30 healthy (n = 120) and 14 dilated (n = 56) AA rings and from 34 human pericardial sections (fresh [n = 68] and Carpentiers solution fixed [n = 68]). In addition, square samples from commercial bovine pericardium (n = 14) were also compared with woven Dacron grafts (n = 24) and tested biaxially. Stress-strain curves (0% to 30%) were generated using a biaxial tensile tester to quantify the anisotropic properties and stiffness of the materials at 37 degrees C. RESULTS: We found significant differences in stiffness and anisotropy among all material types. Fresh and fixed human pericardia, bovine pericardium, and Dacron were 9.5, 7.1, 16.4, and 18.4 times stiffer than dilated AAs, which was 1.3 times stiffer than healthy AAs under physiologic stretch. Only dilated and healthy AAs showed an increase in anisotropic properties with increasing strain. CONCLUSIONS: The significant differences in the mechanical properties among all materials we found are intended to increase the awareness of these differences in materials used in aortic reconstruction surgery. This finding suggests that improvements are needed in prosthetic material design to better mimic native tissue.