Small bite fascial closure technique reduces incisional hernia rates in gynecologic oncology patients.

BACKGROUND: The potential for the technique of small bite fascial closure in mitigating incisional hernias in gynecologic oncology patients still needs to be investigated. OBJECTIVE: To evaluate the impact of closure of small fascial bites compared with prior standard closure on incisional hernia rates in gynecologic oncology patients. METHODS: This is a retrospective cohort study comparing patient outcomes before and after the intervention at a single institution at a comprehensive cancer center. Patients who underwent laparotomy with a vertical midline incision for a suspected or known gynecologic malignancy with a 1-year follow-up were included. The pre-intervention cohort (large bites) had 'mass' or modified running Smead-Jones closure. In contrast, the post-intervention cohort had fascial bites taken 5-8 mm laterally with no more than 5 mm travel (small bites) closure using a 2-0 polydioxanone suture.The primary outcome was the incisional hernias rate determined by imaging or clinical examination within the first year of follow-up. Patient factors and peri-operative variates of interest were investigated for their association with hernia formation through univariate and multivariate analyses. These included age, body mass index (BMI), smoking history, estimated blood loss, pre-operative albumin, American Society of Anesthesia (ASA) physical status classification, or treatment with chemotherapy post-operatively. RESULTS: Of the 255 patients included, the total hernia rate was 12.5% (32/255 patients). Patient characteristics were similar in both cohorts. Small bite closure led to a significant reduction in hernia rates from 17.2% (22/128 patients) to 7.9% (10/127 patients), p=0.025. According to logistic regression modeling, small bite closure (OR=0.40, 95% CI 0.17 to 0.94, p=0.036) was independently associated with lower odds of hernia formation. Other factors associated with increased hernia rates were chemotherapy (OR=3.22, 95% CI 1.22 to 8.51, p=0.019) and obesity (OR=23.4, 95% CI 3.09 to 177, p=0.002). In obese patients, small bite closures led to maximal hernia rate reduction compared with large bites. CONCLUSIONS: The small bite closure technique effectively reduces hernia rates in gynecologic oncology patients undergoing midline laparotomy.

Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024.

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

Implementation of routine venous thromboembolism prophylaxis during neoadjuvant chemotherapy for patients with ovarian cancer.

OBJECTIVE: To compare the venous thromboembolism (VTE) rate in patients with ovarian cancer undergoing neoadjuvant chemotherapy before and after implementing routine thromboprophylaxis. METHODS: This is a quasi-experimental pre-post study evaluating the VTE rate in patients with ovarian cancer who received neoadjuvant chemotherapy following a quality improvement initiative of routine thromboprophylaxis within a single healthcare system that started in January 2017. Patients were excluded if VTE was diagnosed before initiating chemotherapy. Patient factors and perioperative variables of interest were investigated for their association with VTE through univariate and multivariate models. RESULTS: Of the 136 patients in the pre-implementation group, 3.7% (n = 5) received thromboprophylaxis. Of the 154 patients in the post-implementation group, 65.6% (n = 101) received thromboprophylaxis. Provider compliance varied from 51% in 2019 to 79.3% in 2021. The overall rate of VTE, from the start of chemotherapy to the end of treatment, was 21.3% (n = 29) pre- and 8.4% (n = 13) in the post-implementation group (p < 0.01). There was no difference in major bleeding events between groups (0% vs. 0.68%, p = 0.63). On univariate analysis, thromboprophylaxis (OR 0.19; 95% CI 0.07-0.52) and post-implementation period (OR 0.34; 95% CI 0.17-0.69) were associated with a decreased risk of any VTE during primary treatment. On multivariate analysis, only thromboprophylaxis remained significantly associated with reduced VTE rates (aOR 0.19; 95% CI 0.07-0.53). CONCLUSION: Routine thromboprophylaxis during neoadjuvant chemotherapy is associated with reduced risk of VTE throughout primary treatment and is not associated with increased bleeding events.

Acquired factor VIII inhibitor caused by solid tumor malignancy.

•Factor VIII inhibitor can be acquired in gynecologic and other malignancies.•The disorder can develop along any timeline of malignancy diagnosis.•Common presentation is uncontrolled bleeding not managed by common interventions.•Treatment requires hemostatic control and an immunosuppressive regimen.

Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.

Provider compliance with a tailored opioid prescribing calculator in gynecologic surgery.

OBJECTIVE: To evaluate the impact a tailored opioid prescription calculator has on meeting individual patient opioid needs while avoiding opioid over prescriptions. METHODS: Our group previously developed and published an opioid prescribing calculator incorporating patient risk factors (history of depression, anxiety, chronic opioid use, substance abuse disorder, and/or chronic pain) and type of surgery (laparotomy or laparoscopy). This calculator was implemented on 1/1/2021 and its impact on opioid prescriptions was evaluated until 12/31/21. The primary outcome of the present study is to determine prescriber compliance with the calculator (defined as not overprescribing from the number of pills indicated by the calculator). The secondary outcome is to determine the excess prescription rate (defined as proportion of patients reporting more than 3 pills remaining at 30 days post-surgery). Refill rates and pain related patient phone calls were collected. Descriptive statistics were used to summarize the cohort. RESULTS: Of the 355 patients included, 54.7% (N = 194) underwent laparoscopy and 45.4% (N = 161) underwent laparotomy. One hundred and forty-two patients (40%) had at least one risk factor for opioid usage. The median number of opioid pills prescribed following laparoscopy was 3 (range 0-15) and 6 (0-20) after laparotomy. The prescriber compliance was 88.2% and the excess prescription rate was 25.1% (N = 89 patients). CONCLUSIONS: Our tailored opioid calculator has a high prescriber compliance. Implementation of this calculator led to a standardization of tailored opioid prescribing, while limiting the number of over prescriptions. A free web version of the calculator can be easily accessed at www.opioidcalculator.org.

Optimization of postoperative opioid prescriptions in gynecologic oncology: Striking a balance between opioid reduction and pain control.

OBJECTIVE: To implement a quality-improvement initiative to assess the impact various patient and procedural factors have on postoperative opioid use. To develop a tailored opioid prescribing algorithm for gynecologic oncology patients. METHODS: A retrospective cohort study was performed of patients who underwent a laparoscopy or laparotomy procedure for a suspected or known gynecologic malignancy between 3/2019-9/2020. Patients were assessed preoperatively for the presence of suspected risk factors for opioid misuse (depression, anxiety, chronic pain, current opioid use, or substance abuse). Patients completed a 30-day postoperative questionnaire assessing for total opioid pill use and refills requests. Multivariate models were developed to estimate the independent effect of sociodemographic characteristics, risk factors for opioid misuse and procedural factors on patient reported postoperative opioid use. RESULTS: A total of 390 patients were analyzed. Thirty-nine percent (N = 151/390) of patients reported not using opioids after discharge and 5% (N = 20/390) received an opioid refill. For both minimally invasive procedures and laparotomy procedures, body mass index, comorbidities, intraoperative or postoperative complications and final diagnosis of malignancy were not associated with the amount of opioid consumption. However, younger age and history of risk factors for opioid misuse significantly impacted postoperative opioid use. In multivariate analysis, age (p = 0.038) and risk factors (p < 0.001) remained significant after controlling for other factors. CONCLUSIONS: Two out of every five patients did not use opioids after surgery. Younger patients and those with risk factors for opioid misuse need a tailored approach to prescribing opioids to balance the need for adequate pain control with the risk of misuse.

Combined VEGFR and MAPK pathway inhibition in angiosarcoma.

Angiosarcoma is an aggressive malignancy of endothelial cells that carries a high mortality rate. Cytotoxic chemotherapy can elicit clinical responses, but the duration of response is limited. Sequencing reveals multiple mutations in angiogenesis pathways in angiosarcomas, particularly in vascular endothelial growth factor (VEGFR) and mitogen-activated protein kinase (MAPK) signaling. We aimed to determine the biological relevance of these pathways in angiosarcoma. Tissue microarray consisting of clinical formalin-fixed paraffin embedded tissue archival samples were stained for phospho- extracellular signal-regulated kinase (p-ERK) with immunohistochemistry. Angiosarcoma cell lines were treated with the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib, pan-VEGFR inhibitor cediranib, or combined trametinib and cediranib and viability was assessed. Reverse phase protein array (RPPA) was performed to assess multiple oncogenic protein pathways. SVR angiosarcoma cells were grown in vivo and gene expression effects of treatment were assessed with whole exome RNA sequencing. MAPK signaling was found active in over half of clinical angiosarcoma samples. Inhibition of MAPK signaling with the MEK inhibitor trametinib decreased the viability of angiosarcoma cells. Combined inhibition of the VEGF and MAPK pathways with cediranib and trametinib had an additive effect in in vitro models, and a combinatorial effect in an in vivo model. Combined treatment led to smaller tumors than treatment with either agent alone. RNA-seq demonstrated distinct expression signatures between the trametinib treated tumors and those treated with both trametinib and cediranib. These results indicate a clinical study of combined VEGFR and MEK inhibition in angiosarcoma is warranted.

Post-operative gastroparesis following carbohydrate loading in a diabetic patient.

Gastroparesis is a syndrome of delayed gastric emptying associated with nausea, vomiting, and postprandial fullness. Despite multiple etiologies, diabetes is one of the principal causes of gastroparesis. This case report examines a 57 year-old woman with poorly controlled diabetes type II (HbA1c 8.3%) complicated by diabetic nephropathy who was readmitted for gastroparesis after two days following uncomplicated robotic surgical staging for endometrial cancer. Prior to the procedure, the patient had received carbohydrate loading in accordance with our center's enhanced recovery pathway; this resulted in severe acute hyperglycemia, a recognized cause of gastroparesis in women with diabetes. During her readmission, she improved with bowel rest and optimization of glycemic control. This case suggests that routine pre-operative carbohydrate loading should be used with caution in poorly controlled diabetic patients.

Clinical significance of homologous recombination deficiency score testing in endometrial Cancer.

BACKGROUND: Homologous recombination deficiency (HRD) score is related to chemotherapy response in some cancers, but its role in endometrial cancer in not known. We determined frequency and clinical significance of alterations in the HR pathway in endometrial cancer. METHODS: 253 endometrioid endometrial adenocarcinoma (EEA) samples from two independent cohorts (discovery and replication) were tested for HRD score using the Myriad HRD assay, microsatellite instability (MSI) and tumor mutation burden (TMB) using a next generation sequencing assay. HRD scores were also generated on endometrial cancer cell lines and in vivo response to olaparib was assessed. RESULTS: ROC curves were employed to determine optimal cutoffs of HRD in relation to survival impact in endometrial cancer and a cutoff of HRD ≥ 4 was suggested for DFS using the discovery cohort. Patients from two independent cohorts with HRD score ≥ 4 trended toward worse survival as compared to those with HRD score < 4. Both cohorts were further separated into four groups according to molecular subtypes (TMB positive; MSI positive; HRD positive; all others). When grouped by molecular subtype, there was a significant difference between groups using an HRD ≥4 cutoff in the initial (p = 0.0024) and replication (p = 0.042) cohorts. The Hec1a model (HRD score = 19) was highly sensitive to olaparib in in vitro and in vivo experiments. CONCLUSIONS: High HRD score was associated with worse DFS in our patient cohort. These findings suggest that HRD score may have clinical utility in patients with advanced or recurrent endometrial cancer.