Search

Background: No guidelines exist regarding the management of the uninvolved uterus or adnexa (fallopian tubes and/or ovaries) in patients with peritoneal metastases (PM) from non-gynecologic malignancies. It is unclear whether salpingo-oophorectomy, hysterectomy, or both should be performed when a complete pelvic peritonectomy is otherwise warranted., Methods: A 25-item electronic survey was sent to 225 surgeons worldwide who routinely perform cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). Participants were recruited through listservs of expert groups. Individual surgeon approaches to the management of the grossly uninvolved uterus and adnexa in pre- and post-menopausal women with PM from low- and high-grade appendiceal neoplasms, colorectal cancer, and peritoneal mesothelioma were collected using a 5-point Likert scale., Results: A total of 135 complete responses (60% response rate) were obtained from surgeons practicing in 27 countries. Respondents reported a median practice of 10 years (interquartile range [IQR] 6-15 years) and a median performance of 20 (IQR 12-30) CRS/HIPEC operations per year. Rates of salpingo-oophorectomy differed by histology and a woman's menopausal status, ranging from 29 to 42% in pre-menopausal women to 71-77% in post-menopausal women (P < 0.001). Notably, the number of surgeons who would perform a hysterectomy was lower, ranging from 12 to 27% for pre-menopausal women and from 32 to 44% for post-menopausal women, dependent on histology (P < 0.001)., Conclusions: Surgeons are overall more aggressive with adnexal resection than with hysterectomy in both pre- and post-menopausal women with PM from non-gynecologic malignancies. Further prospective studies are required to determine the best approach to optimize surgical and oncologic outcomes while also accounting for the fertility and hormonal impact., (© 2024. Society of Surgical Oncology.)

Recent advances in molecular analyses of ovarian cancer have revealed a wealth of promising tumour-specific biomarkers, including protein, DNA mutations and methylation; however, reliably detecting such alterations at satisfactorily high sensitivity and specificity through low-cost methods remains challenging, especially in early-stage diseases. Here we present PapDREAM, a new approach that enables detection of rare, ovarian-cancer-specific aberrations of DNA methylation from routinely-collected cervical Pap specimens. The PapDREAM approach employs a microfluidic platform that performs highly parallelized digital high-resolution melt to analyze locus-specific DNA methylation patterns on a molecule-by-molecule basis at or near single CpG-site resolution at a fraction (< 1/10th) of the cost of next-generation sequencing techniques. We demonstrate the feasibility of the platform by assessing intermolecular heterogeneity of DNA methylation in a panel of methylation biomarker loci using DNA derived from Pap specimens obtained from a cohort of 43 women, including 18 cases with ovarian cancer and 25 cancer-free controls. PapDREAM leverages systematic multidimensional bioinformatic analyses of locus-specific methylation heterogeneity to improve upon Pap-specimen-based detection of ovarian cancer, demonstrating a clinical sensitivity of 50% at 99% specificity in detecting ovarian cancer cases with an area under the receiver operator curve of 0.90. We then establish a logistic regression model that could be used to identify high-risk patients for subsequent clinical follow-up and monitoring. The results of this study support the utility of PapDREAM as a simple, low-cost screening method with the potential to integrate with existing clinical workflows for early detection of ovarian cancer. KEY POINTS: We present a microfluidic platform for detection and analysis of rare, heterogeneously methylated DNA within Pap specimens towards detection of ovarian cancer. The platform achieves high sensitivity (fractions <0.00005%) at a suitably low cost (∼$25) for routine screening applications. Furthermore, it provides molecule-by-molecule quantitative analysis to facilitate further study on the effect of heterogeneous methylation on cancer development., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Venous thromboembolism (VTE) is a major cause of both morbidity and mortality in patients with cancer. Venous thromboembolism, which includes both deep vein thrombosis and pulmonary embolism, affects a sizable portion of patients with malignancy and can have potentially life threatening complications. Accurate assessment of risk as well as diagnosis and treatment of this process is paramount to preventing death in this high risk population. Various risk models predictive of venous thromboembolism in patients with cancer have been developed, and knowledge of these rubrics is essential for the treating oncologist. Subgroups of particular interest are inpatients receiving chemotherapy, postoperative patients after surgical debulking, and patients undergoing radiotherapy. Numerous newer drugs have become available for the prevention of venous thromboembolism in patients with cancer who are at high risk of developing the disease. These include the class of drugs called direct oral anticoagulants, (DOACs) which do not require the same monitoring that other modalities have previously required and are taken by mouth, preventing the discomfort associated with subcutaneous strategies. The appropriate risk stratification and intervention to prevent venous thromboembolism are vital to the treatment of patients with cancer., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To compare quality of life (QOL) among patients with endometrial intraepithelial neoplasia or early-stage endometrial cancer and stress urinary incontinence (SUI) who chose to have concomitant surgery with cancer surgery alone., Methods: A multicenter, prospective cohort study was conducted across eight U.S. sites. Potentially eligible patients were screened for SUI symptoms. Those who screened positive were offered referral to urogynecology and incontinence treatment, including concomitant surgery. Participants were categorized into two groups: 1) concomitant cancer and SUI surgery or 2) cancer surgery alone. The primary outcome was cancer-related QOL as measured by the FACT-En (Functional Assessment of Cancer Therapy-Endometrial) (range 0-100; higher score indicates better QOL). The FACT-En and questionnaires assessing urinary symptom-specific severity and effects were assessed before surgery and 6 weeks, 6 months, and 12 months after surgery. Adjusted median regression accounting for clustering was used to examine the relationship between SUI treatment group and FACT-En scores., Results: Of 1,322 (53.1%) patients, 702 screened positive for SUI with 532 analyzed; 110 (21%) chose concomitant cancer and SUI surgery, and 422 (79%) chose cancer surgery alone. FACT-En scores increased for both the concomitant SUI surgery and cancer surgery-only groups from the preoperative to the postoperative period. After adjustment for timepoint and preoperative covariates, the median change in FACT-En score (postoperative-preoperative) was 1.2 points higher (95% CI -1.3 to 3.6) for the concomitant SUI surgery group compared with the cancer surgery-only group across the postoperative period. Median time until surgery (22 days vs 16 days; P <.001), estimated blood loss (150 mL vs 72.5 mL; P <.001), and operative time (185.5 minutes vs 152 minutes; P <.001) were all greater for the concomitant cancer and SUI surgery group compared with the cancer-only group, respectively., Conclusion: Concomitant surgery did not result in improved QOL compared with cancer surgery alone for endometrial intraepithelial neoplasia and patients with early-stage endometrial cancer with SUI. However, FACT-En scores were improved in both groups., Competing Interests: Financial Disclosure Kyle Wohlrab reports receiving payment from Boston Scientific. His spouse (Katina Robison, MD) is the lead author of this article and received a PCORI grant to fund the project. Holly E. Richter disclosed the following: ongoing research funding: NIH/NIA; NIH/University of Pennsylvania; NIH/University of Minnesota; NICHD/University of Texas at Austin, NIH/UT Southwestern; Renovia; EBT Medical; Reia. Past: NICHD; NIDDK/Univ North Carolina; Allergan; Renovia; Pelvalon. Other disclosures: DSMB member: BlueWind Medical; UpToDate: royalties, Board of Directors: AUGS and WorldWide Fistula Fund; editorial duties: IUJO and Obstetrics & Gynecology . Carolyn McCourt reports receiving a payment from UpToDate. Jerry Lowder’s institution received grant support from NIH-NIDDK. He received payment from Hanson Curran LLP for medicolegal review and expert testimony. Gena Dunivan's institution received payment from Renovia. David Rahn’s institution received payment from the National Institute on Aging (NIA), National Institute of Child Health and Human Development (NICHD), and Pfizer, Inc. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Plasma energy ablation vaporizes tissues similar to carbon dioxide laser ablation, but is not hindered by the unique hazards and regulation of laser technology. We aimed to evaluate the complication rate and effectiveness of plasma versus laser ablation in the treatment of vulvovaginal high-grade squamous intra-epithelial lesions (HSIL)., Methods: We performed a retrospective cohort study of women treated with plasma or carbon dioxide laser ablation for histologically proven HSIL of the vulva or vagina from January 2014 to October 2019 at a single institution. Demographic factors, surgical characteristics, and complications were compared by ablation type using Fisher's exact tests. Recurrence-free survival was evaluated by ablation type using Kaplan-Meier curves, weighted log-rank tests, and Cox proportional hazards ratio estimates., Results: Forty-two women were included; 50% underwent plasma and 50% underwent carbon dioxide laser ablation. Demographic factors were similar between the groups. 50% (n=21) were immunosuppressed, 45.2% (n=19) had prior vulvovaginal HSIL treatment, and 35.7% (n=15) were current smokers. Most women (n=25, 59.5%) were treated for vulvar HSIL, 38.1% (n=16) for vaginal HSIL. Complication rates did not differ by treatment: 9.5% (n=2) for laser ablation versus 4.8% (n=1) for plasma ablation (p = 1.0). Over a median follow-up time of 29.3 months (IQR 11.0-45.0 months), recurrence rates were similar: 28.6% in the laser ablation group versus 33.3% in the plasma ablation group (weighted log rank p=0.43; 24-month HR 0.54, 95% CI 0.15 to 2.01)., Conclusion: Plasma energy ablation of vulvovaginal HSIL has similar complication rates and recurrence risk to carbon dioxide laser ablation. This technique could be considered as an alternative treatment modality for vulvovaginal HSIL and warrants further investigation., Competing Interests: Competing interests: RS reports personal consulting fees from Astra Zeneca and is on an advisory board for GlaxoSmithKline, unrelated to the present work., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Declaration of Competing Interest All authors have nothing to disclose.

The COVID-19 pandemic has challenged our ability to provide timely surgical care for our patients. In response, the U.S. Surgeon General, the American College of Srugeons, and other surgical professional societies recommended postponing elective surgical procedures and proceeding cautiously with cancer procedures that may require significant hospital resources and expose vulnerable patients to the virus. These challenges have particularly distressing for women with a gynecologic cancer diagnosis and their providers. Currently, circumstances vary greatly by region and by hospital, depending on COVID-19 prevalence, case mix, hospital type, and available resources. Therefore, COVID-19-related modifications to surgical practice guidelines must be individualized. Special consideration is necessary to evaluate the appropriateness of procedural interventions, recognizing the significant resources and personnel they require. Additionally, the pandemic may occur in waves, with patient demand for surgery ebbing and flowing accordingly. Hospitals, cancer centers and providers must prepare themselves to meet this demand. The purpose of this white paper is to highlight all phases of gynecologic cancer surgical care during the COVID-19 pandemic and to illustrate when it is best to operate, to hestitate, and reintegrate surgery. Triage and prioritization of surgical cases, preoperative COVID-19 testing, peri-operative safety principles, and preparations for the post-COVID-19 peak and surgical reintegration are reviewed., Competing Interests: Declaration of competing interest Dr. Warner Huh reports personal fees from LICOR, outside the submitted work and Expert Witness: Skadden (on behalf of Intuitive Surgical). Dr. Bhavana Pothuri reports grants, personal fees and non-financial support outside the submitted work; institutional PI for industry sponsored trials from Tesaro/GSK, AstraZeneca, Merck, Genentech/Roche, and Clovis Oncology. Compensated advisory boards include Tesaro/GSK, AstraZeneca, and Eisai. Dr. Mario Leitao reports personal fees from JnJ/Ethicon, outside the submitted work and Dr. Leitao is an ad hoc speaker for Intuitive Surgical, Inc. Dr. Joshua Kesterson reports personal fees from GSK/Tesaro, personal fees from Clovis Oncology, outside the submitted work. Dr. Jason Wright reports grants from Merck, personal fees from Clovis Oncology, outside the submitted work. Dr. Amer Karam reports personal fees from Clovis Oncology, personal fees from GSK, personal fees from Astra Zeneca, personal fees from UpToDate, outside the submitted work. Dr. S. Diane Yamada reports other from LEAP Therapeutics, outside the submitted work. All other authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To determine whether the rate of sentinel lymph node (SLN) dissections that do not yield a lymph node on pathological analysis ('empty packet dissection') changes with increasing surgeon experience in the setting of patients undergoing minimally invasive hysterectomy and SLN mapping using indocyanine green dye for endometrial cancer., Methods: All patients undergoing SLN mapping using indocyanine green dye at the time of minimally invasive hysterectomy for endometrial cancer or complex atypical hyperplasia were identified between January 2013 and September 2017 at our institution. All surgeons had prior experience performing SLN mapping for endometrial cancer using other methods. The rate of empty packet dissections and SLN counts were evaluated using a logistic regression model analysis., Results: In total, 236 patients undergoing SLN mapping for either endometrial cancer (85%) or complex atypical hyperplasia (15%) were identified from a prospectively maintained database. When examining all six surgeons together, the percentage of empty packet dissections decreased with increasing number of procedures performed. Each additional procedure was associated with a 3.6% reduction in the odds of an empty packet SLN dissection. After adjusting for individual surgeons, each additional procedure was associated with a 4.9% reduction in the odds of an empty packet. The expected odds of an empty packet after 10 additional procedures decreased by 40.1% (95% CI 12.4% to 58.6%). The addition of two covariates (age and body mass index) did not contribute significantly to the model (likelihood ratio test: X 2 =2.75, p=0.25). The rate of empty packets appeared to stabilize after approximately 30 procedures. The number of SLNs removed did not change with increasing surgeon experience., Conclusion: The rate of empty packet SLN dissections using indocyanine green dye decreases with increasing number of procedures. This stabilizes after 30 procedures, suggesting completion of a learning curve., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Mutualistic interactions are powerful drivers of biodiversity on Earth that can be represented as complex interaction networks that vary in connection pattern and intensity. One of the most fascinating mutualisms is the interaction between hummingbirds and the plants they visit. We conducted an exhaustive search for articles, theses, reports, and personal communications with researchers (unpublished data) documenting hummingbird visits to flowers of nectar-rewarding plants. Based on information gathered from 4532 interactions between 292 hummingbird species and 1287 plant species, we built an interaction network between nine hummingbird clades and 100 plant families used by hummingbirds as nectar resources at a continental scale. We explored the network architecture, including phylogenetic, morphological, biogeographical, and distributional information. As expected, the network between hummingbirds and their nectar plants was heterogeneous and nested, but not modular. When we incorporated ecological and historical information in the network nodes, we found a generalization gradient in hummingbird morphology and interaction patterns. The hummingbird clades that most recently diversified in North America acted as generalist nodes and visited flowers with ornithophilous, intermediate and non-ornithophilous morphologies, connecting a high diversity of plant families. This pattern was favored by intermediate morphologies (bill, wing, and body size) and by the low niche conservatism in these clades compared to the oldest clades that diversified in South America. Our work is the first effort exploring the hummingbird-plant mutualistic network at a continental scale using hummingbird clades and plant families as nodes, offering an alternative approach to exploring the ecological and evolutionary factors that explain plant-animal interactions at a large scale., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Enhanced Recovery After Surgery (ERAS) programs are mechanisms for achieving value-based improvements in surgery. This report provides a detailed analysis of the impact of an ERAS program on patient outcomes as well as quality and safety measures during implementation on a gynecologic oncology service at a major academic medical center., Methods: A retrospective review of gynecologic oncology patients undergoing elective laparotomy during the implementation phase of an ERAS program (January 2016 through December 2016) was performed. Patient demographics, surgical variables, postoperative outcomes, and adherence to core safety measures, including antimicrobial and venous thromboembolism (VTE) prophylaxis, were compared to a historical patient cohort (January 2015 through December 2015). Statistical analyses were performed using t-tests, Wilcoxon rank sum tests, and Chi squared tests., Results: The inaugural 109 ERAS program participants were compared to a historical patient cohort (n=158). There was no difference in BMI, race, malignancy, or complexity of procedure between cohorts. ERAS patients required less narcotics (70.7 vs 127.4, p=0.007, oral morphine equivalents) and PCA use (32.1% vs. 50.6%, p=0.002). Despite this substantial reduction in narcotics, ERAS patients did not report more pain and in fact reported significantly less pain by postoperative day 3. There were no differences in length of stay (5days), complication rates (13.8% vs. 20.3%, p=0.17) or 30-day readmission rates (9.5 vs 11.9%, p=0.54) between ERAS and historical patients, respectively. Compliance with antimicrobial prophylaxis was 97.2%. However, 33.9% of ERAS patients received substandard preoperative VTE prophylaxis., Conclusions: ERAS program implementation resulted in reductions in narcotic requirements and PCA use without changes in length of stay or readmission rates. Compliance should be diligently audited during the implementation phase of ERAS programs, with special attention to adherence to pre-existing core safety measures., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To identify risk factors for surgical site infection and to define rates associated with cytoreductive surgery before and after implementation of an infection prevention bundle., Methods: We conducted a prospective quality improvement study. Patients who underwent ovarian, fallopian tube, or peritoneal cancer cytoreductive surgery at an academic tertiary care center from April 2014 to April 2016 were prospectively enrolled. Patient demographics, surgical variables, and surgical site infection rates were compared with a historical cohort after introduction of a 5-point infection prevention bundle, including: 1) preoperative and intraoperative skin preparation with 4% chlorhexidine and intraoperative vaginal preparation with 4% chlorhexidine; 2) preoperative use of oral antibiotics and mechanical bowel preparation; 3) appropriate timing of intraoperative antibiotics; 4) adoption of enhanced sterile surgical techniques for colon procedures and incisional closure; and 5) perioperative incision management., Results: During the study period, 219 women underwent surgery: 91 prebundle and 128 treated in the postbundle period. Stage, body mass index, proportion of patients undergoing colon or upper abdominal surgery, and estimated blood loss were not different between the cohorts. Overall, the surgical site infection rate prebundle was 18 (20%); this was reduced to four (3%) postbundle (odds ratio [OR] 0.13, 95% CI 0.037-0.53; P<.001). Patients who underwent a colon resection prebundle had an infection rate of 14 (33%) compared with three (7%) in the postbundle group (OR 0.14, 95% CI 0.037-0.53; P<.001). Additionally, rates of surgical site infection-related hospital readmission were also lower in the postbundle (4/128 [3%]) compared with the prebundle group (12/91 [13%]; P=.005)., Conclusion: Infection is common after ovarian cancer cytoreductive surgery. Implementation of a 5-point surgical site infection prevention bundle in women undergoing ovarian cancer operations was associated with dramatically decreased infection rates and lower hospital readmission rates.

Endometrial clear cell carcinoma (CC) is an uncommon tumor and often carries a poor prognosis. It has histologic features that overlap with other endometrial carcinomas and is frequently misclassified. Accurate classification is crucial, however, to improve treatment options. The objectives of this study were (1) to assess diagnostic interobserver variability among 5 gynecologic pathologists for tumors originally diagnosed as CC or with a component of CC (n=44); (2) to determine the utility of immunohistochemical markers estrogen receptor and HNF-1β; and (3) to detect mutations in select genes. Clinical data and morphologic features were also recorded. Agreement among reviewers was only moderate: only 46% of the original CC remained classified as such. After reclassification, estrogen receptor was positive in 8% of CC, 67% of endometrioid carcinomas (EC), and 47% of serous carcinomas (SC). Sensitivities of HNF-1β in CC, SC, and EC were 62%, 27%, and 17%, respectively, whereas specificity for CC versus EC or SC was 78%. Mutations in PIK3CA, PIK3R1, PTEN, KRAS, and NRAS were detected in 41% of 37 cases that had adequate material for study. At least 1 mutation was identified in 33% of CC, 67% of EC, and 33% of SC. This group of patients had poor outcomes: 72% of the patients with follow-up information had died of disease. In summary, this study suggests that the current pool of CC is a heterogeneous group of tumors from the morphologic, immunophenotypic, and molecular point of views and that only a percentage of them represent true CC.