Need for formalized robotic training and curriculum in obstetrics and gynecology residency: an examination of current resident outlooks and perspectives.

The objectives of this study were to evaluate current robotic surgery training methodologies for ACGME-accredited obstetrics and gynecology (OB/GYN) residency programs, better understand current resident perspectives, and explore potential areas for improvement within resident education. A cross-sectional study was done of ACGME-accredited OB/GYN residents in the 2023-2024 academic year. The study was done on a national setting via web-based survey. 75 surveys were included. The study was conducted via a 33-question survey study using a mixture of multiple choice, multiple answer, and Likert scale questions. Participants noted that 98.7% of their institutions perform robotic surgery and 90.7% have access to robotic console trainers. Outside of the operating room, slightly more than half of participants (57.3%) have formalized robotics training curriculums. A variety of training modalities were noted to be utilized by residents with the most helpful being hands-on training (67.7%) followed by dual-assist console (45.6%). The least helpful was noted to be online modules (58.7%). Most residents either strongly agree (45.3%) or agree (36.0%) that standardized robotics curriculums should be implemented for all OB/GYN residency programs. The largest barriers to completion of this training were noted to be attending comfort with resident participation in the case (74.0%), personal time (58.9%), and availability or access to trainers (42.5%). A formalized and standardized robotic training curriculum should be considered for OB/GYN residents with a multi-modal model utilizing a combination of training modalities as well as dedicated didactic hours.

A case of radiation-induced bullous pemphigoid in a vulvar cancer patient.

•Radiation-induced bullous pemphigoid is a rare autoimmune disease.•There is only one prior documented case of radiation-induced bullous pemphigoid in a vulvar cancer patient.•A multidisciplinary approach is critical to identify and treat bullous pemphigoid.

Phase I trial of daily subcutaneous SPL-108 injections in combination with paclitaxel in patients with platinum resistant CD44+ advanced ovarian epithelial cancer.

OBJECTIVE: Preclinical evidence and early clinical trials have demonstrated the activity of SPL-108, a targeted agent that inhibits CD44 mediated induction of multidrug resistance specifically to paclitaxel and platinum agents. We conducted a phase I, open label, dose escalation study of the safety and tolerability of the combination of SPL-108 with weekly paclitaxel in patients with platinum resistant CD44+ ovarian, primary peritoneal, or fallopian tube cancer. METHODS: Patients with platinum resistant histologically proven epithelial ovarian, primary peritoneal, or fallopian tube cancers and measurable disease according to RECIST (Response Evaluation Criteria in Solid Tumours) version 1.1 were selected. Tumors were tested for CD44 expression for eligibility, defined as strong (+++) or moderate (++) staining in ≥20% of the tumor tissue or diffuse + staining. Patients were treated with daily and then twice daily SPL-108 subcutaneous injections and weekly intravenous paclitaxel on days 1, 8, and 15 of a 28 day cycle. Endpoints included safety, determination of maximum tolerated dose, and efficacy. Tumors underwent comprehensive genomic profiling, and cell lines and western blotting were used to study markers of response. RESULTS: We screened 16 patients, and 14 were enrolled based on CD44+ expression. A total of 86% of patients had high grade serous tumors and all had received multiple prior therapies. There were no grade 4-5 toxicities. One patient had grade 3 peripheral sensory neuropathy attributed to paclitaxel and one patient developed presumed colonic perforation attributed to the study drug. No dose reductions or treatment discontinuations were required. All patients tolerated the maximum planned dose; no maximum tolerated dose was reached. Overall response rate was 36%; 5 (36%) patients had partial response and 5 (36%) patients had stable disease. CONCLUSIONS: The combination of SPL-108 with weekly paclitaxel was safe and well tolerated. Encouraging antitumor activity was observed, with 72% of patients deriving a clinical benefit. TRIAL REGISTRATION: NCT03078400.

Carotenoids in Milk and the Potential for Dairy Based Functional Foods.

Carotenoids are a family of over 1100 known natural pigments synthesized by plants, algae, fungi and bacteria. Dietary intake of carotenoids is necessary for mammals as they cannot be synthesized in the body. In cows, the nature of the diet consumed strongly influences the composition of milk produced and this includes carotenoid concentration and profile. Fresh forage is the richest source of carotenoids for cows. The main carotenoids identified in forages are lutein, ß-carotene, zeaxanthin and epilutein. Manipulating cow feed via carotenoid supplementation increases the carotenoid content of bovine milk. In humans, carotenoids have anti-oxidant, anti-inflammatory and provitamin A activity. Lutein is a major carotenoid in human milk and the brain tissue of adults and infants. Lutein and zeaxanthin are linked to improved eye health and cognitive function. Traditionally for humans, fruit and vegetables have been the main source of carotenoid intake. Functional foods present an opportunity to incorporate these naturally occurring compounds into milk products for added health benefits, widening the range of dietary sources of carotenoids. We offer an overview of the literature to date on carotenoid-fortified dairy products and infant formula. This review will describe and summarize the key mechanisms by which the carotenoid profile of bovine milk can be manipulated. We present findings on the origin and role of carotenoids in bovine and human milk, outline factors that impact the carotenoid content of milk, evaluate carotenoid-fortified milk products and discuss the associated challenges, such as bioaccessibility and stability.

Vaginal mucositis related to immunotherapy in endometrial cancer.

Immunotherapy, specifically immune checkpoint inhibitors (ICPi), has revolutionized our approach to treating all solid tumors, including gynecologic malignancies. Compared to standard chemotherapy, the adverse events associated with immunotherapies, are often mild and localized, although more severe systemic responses can also occur. While dermatitisdermatitis is a most commonly reported side effect of ICPi therapy, cutaneous toxicities have a range of clinical manifestations and can provide a challenge in an otherwise favorable treatment protocol. There have been few documented cases of mucositis caused by ICPi therapy and to our knowledge, no documented case of an ICPi therapy causing vaginal mucositis. As such, we present a case of a patient with metastatic uterine serous carcinoma (USC) treated with immunotherapy, who developed grade 3 vaginal mucositis. This is a case presentation of a 67-year-old woman with a history of stage I metastatic uterine serous carcinoma who was initially treated with a hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. Eight months after surgery, patient was found to have a vaginal recurrence treated with external beam radiation therapy and vaginal brachytherapy, as well as port site recurrence treated with resection and 6 cycles of systemic chemotherapy with Carboplatin and Paclitaxel. The patient was found to have progression of her disease and was treated with a combinatorial therapy using PD-L1 inhibitor and TK inhibitor. Patient tolerated first two cycles of treatment without severe side effects. Nine days after administration of the second cycle, the patient reported new onset of severe non-radiating vaginal and perineal pain, that worsened with sitting down, and was refractory to pain medications. Pelvic examination revealed multiple, deep, erythematous ulcerations on the vaginal mucosa involving the left and anterior vaginal introitus, distal vagina and necrosis around the periurethral area, consistent with grade 3 mucositis. The treatment was immediately discontinued, and the patient was started on prednisone 100 mg by mouth daily for 7 days, which was tapered over the course of 10 days and Gabapentin and Oxycodone were given for pain control. The patient started to report improvement in symptoms after 3 weeks and re-examination in 1 month showed decreased amount of fibrinous material involving 50% of the lesions, indicating that the initial grade 3 mucositis had improved to grade 1. As immunotherapy is becoming more widely used in gynecologic and other malignancies, providers need to be aware of rare but significant complications associated with these therapies. Such toxicities should be correctly identified and treated appropriately and expediently. Most patients will continue to benefit from administered immunotherapy and often times can be restarted once the toxicities are alleviated. To our knowledge, this is a first reported case of vaginal mucositis associated with immunotherapy treatment with ICPi in a patient with gynecologic malignancy.

Assessing the immediate impact of COVID-19 on surgical oncology practice: Experience from an NCI-designated Comprehensive Cancer Center in the Northeastern United States.

BACKGROUND: The effects of the coronavirus disease 2019 (COVID-19) pandemic on surgical oncology practice are not yet quantified. The aim of this study was to measure the immediate impact of COVID-19 on surgical oncology practice volume. METHODS: A retrospective study of patients treated at an NCI-Comprehensive Cancer Center was performed. "Pre-COVID" era was defined as January-February 2020 and "COVID" as March-April 2020. Primary outcomes were clinic visits and operative volume by surgical oncology subspecialty. RESULTS: Abouyt 907 new patient visits, 3897 follow-up visits, and 644 operations occurred during the study period. All subspecialties experienced significant decreases in new patient visits during COVID, though soft tissue oncology (Mel/Sarc), gynecologic oncology (Gyn/Onc), and endocrine were disproportionately affected. Telehealth visits increased to 11.4% of all visits by April. Mel/Sarc, Gyn/Onc, and Breast experienced significant operative volume decreases during COVID (25.8%, p = 0.012, 43.6% p < 0.001, and 41.9%, p < 0.001, respectively), while endocrine had no change and gastrointestinal oncology had a slight increase (p = 0.823) in the number of cases performed. CONCLUSIONS: The effects of the COVID-19 pandemic are wide-ranging within surgical oncology subspecialties. The addition of telehealth is a viable avenue for cancer patient care and should be considered in surgical oncology practice.

A curve-shift technique for the use of non-conservative organic tracers in constructed wetlands.

Understanding the flow behaviour and accounting for time in constructed wetlands is necessary for the modelling and design of these systems. The addition of a tracer into the feed of a horizontal subsurface flow wetland allows the researcher to understand the flow of the fluid through the system, especially if the mass of the tracer is conserved (i.e. the mass of tracer injected is equal to the mass of tracer leaving the system). Conservative tracers, however, may pose a problem when it comes to the disposal of the effluent of the system if they are hazardous to the environment. In this study, the use of benzoate as a non-conservative degradable hydraulic tracer was investigated. The response curve of such a tracer is distorted due to its degradation within the wetland and hence the mass leaving the system is not equal to the mass injected. As a result, the typical hydraulic performance parameters obtained from tracer-response curves cannot be accurately calculated. In this paper, a curve-shift technique was developed by using a benzoate step-change curve as an input and using mathematical techniques to transform it into a conservative tracer-response curve. This was done through establishing a mathematical relationship between the retardation and hydrodynamic dispersion of benzoate and a known conservative tracer, uranine. This methodology was tested by conducting a dual tracer study using both benzoate and uranine and comparing the shifted benzoate response curve with the uranine response curve. Hydraulic parameters including mean residence time, effective volume ratio and hydraulic efficiency for each of these tracers were also compared.

Evaluating unplanned readmission and prolonged length of stay following minimally invasive surgery for endometrial cancer.

OBJECTIVE: To evaluate risk factors for 30-day unplanned readmission and increased length of stay (LOS) following minimally invasive surgery (MIS) for endometrial cancer. METHODS: This was a retrospective, case-control study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). Multivariable logistic regression was used to assess perioperative variables associated with readmission and increased LOS after MIS for endometrial cancer. RESULTS: The study population included 10,840 patients who met the criteria of having undergone MIS with a resultant endometrial malignancy confirmed on postoperative pathology. Common reasons for readmission included organ/space surgical site infection (65 cases), sepsis/septic shock (19 cases), and venous thromboembolism (20 cases). Notable risk factors for readmission included (Odds Ratio, Confidence Interval, p-value): dialysis dependence (6.77, 2.51-17.80, <0.01), increased length of stay (3.00, 2.10-4.10, <0.01), and preoperative weight loss (2.80, 1.06-7.17, 0.03); notable risk factors for increased LOS: ascites (8.51, 2.00-36.33, <0.01), operation duration >5 h (6.93, 5.29-9.25, <0.01), and preoperative blood transfusion (5.37, 2.05-14.04, <0.01). CONCLUSIONS: Identification of risk factors for adverse postoperative outcomes is necessary to inform and improve standards of care in MIS for endometrial cancer. Using nationally reported data from the ACS NSQIP, this study identifies independent risk factors for unplanned readmission and prolonged LOS, and in doing so, highlights potential avenues for quality improvement.

HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): A Randomized Controlled Trial of Hyperbaric Oxygen to Prevent Osteoradionecrosis of the Irradiated Mandible After Dentoalveolar Surgery.

PURPOSE: Hyperbaric oxygen (HBO) has been advocated in the prevention and treatment of osteoradionecrosis (ORN) of the jaw after head and neck radiation therapy, but supporting evidence is weak. The aim of this randomized trial was to establish the benefit of HBO in the prevention of ORN after high-risk surgical procedures to the irradiated mandible. METHODS AND MATERIALS: HOPON was a randomized, controlled, phase 3 trial. Participants who required dental extractions or implant placement in the mandible with prior radiation therapy >50 Gy were recruited. Eligible patients were randomly assigned 1:1 to receive or not receive HBO. All patients received chlorhexidine mouthwash and antibiotics. For patients in the HBO arm, oxygen was administered in 30 daily dives at 100% oxygen to a pressure of 2.4 atmospheres absolute for 80 to 90 minutes. The primary outcome measure was the diagnosis of ORN 6 months after surgery, as determined by a blinded central review of clinical photographs and radiographs. The secondary endpoints included grade of ORN, ORN at other time points, acute symptoms, pain, and quality of life. RESULTS: A total of 144 patients were randomized, and data from 100 patients were analyzed for the primary endpoint. The incidence of ORN at 6 months was 6.4% and 5.7% for the HBO and control groups, respectively (odds ratio, 1.13; 95% confidence interval, 0.14-8.92; P = 1). Patients in the hyperbaric arm had fewer acute symptoms but no significant differences in late pain or quality of life. Dropout was higher in the HBO arm, but the baseline characteristics of the groups that completed the trial were comparable between the 2 arms. CONCLUSIONS: The low incidence of ORN makes recommending HBO for dental extractions or implant placement in the irradiated mandible unnecessary. These findings are in contrast with a recently published Cochrane review and previous trials reporting rates of ORN (non-HBO) of 14% to 30% and challenge a long-established standard of care.

Rapid spontaneous regression of acute-onset vulvar intraepithelial neoplasia 3 in young women: a case series.

OBJECTIVE: Vulvar intraepithelial neoplasia 3 (VIN 3)/vulvar carcinoma in situ is currently treated by surgical excision, laser ablation, or topically with 5-fluorouracil or imiquimod. The rate of progression of untreated VIN 3/vulvar carcinoma in situ to invasive cancer is significant, although difficult to assess, because most patients undergo treatment. The peak incidence of invasive carcinoma of the vulva occurs in the sixth decade, which may indicate that human papillomavirus (HPV)-related preinvasive disease in the younger population has a lower progression rate. However, the risk of invasive disease cannot be disregarded. METHODS: This is a case series of complete spontaneous resolution of untreated VIN 3/vulvar carcinoma in situ in 5 healthy women aged 20 to 36 years from a single community gynecologic oncologist practice from 2006 to 2010. RESULTS: Complete spontaneous regression of acute VIN 3/vulvar carcinoma in situ was reported in 6 healthy young women aged 20 to 36 years. New sexual partners were reported in 2 of the 6 patients preceding the onset of vulvar lesions within 6 months. All patients were nonsmokers, healthy without known immunocompromise, and noted the acute onset of vulvar lesions. Vulvar intraepithelial neoplasia 3/vulvar carcinoma in situ was diagnosed on biopsy and confirmed on independent review. All lesions were multifocal in nature. Time to spontaneous regression was 6, 6, 8, 12, 18, and 20 weeks after initial biopsy. No patient received the HPV vaccine. Recurrence has not been noted in any of the patients within the follow-up period of 6 to 60 months. CONCLUSIONS: Short-term follow-up with conservative management of acute-onset VIN 3/vulvar carcinoma in situ in this young patient population correlates with similar treatment strategies for HPV-related cervical intraepithelial neoplasia of the cervix and may prevent disfigurement, pain, and complications associated with the current recommended therapeutic modalities. The timing of intervention for VIN 3/vulvar carcinoma in situ in the young population needs clarification. Future studies are in order.

Activity of Hoechst 33258 against Pneumocystis carinii f. sp. muris, Candida albicans, and Candida dubliniensis.

Hoechst 33258 is a compound that binds nucleic acids. We report that Hoechst 33258 exhibits antimicrobial activity against Pneumocystis carinii f. sp. muris in a mouse model for P. carinii pneumonia and against Candida albicans and Candida dubliniensis in vitro. Relative to saline treatment, a 14-day, daily treatment of mice with 37.5 mg of Hoechst 33258/kg of body weight after inoculation with P. carinii reduced by about 100-fold the number of P. carinii organisms detected by either PCR or by microscopy after silver staining. For comparison, treatment based on a dose of 15 to 20 mg of the trimethoprim component in trimethoprim-sulfamethoxazole/kg reduced the number of P. carinii by about fourfold. In vitro inhibition of P. carinii group I intron splicing was observed with a 50% inhibitory concentration (IC50) of 30 microM in 2 or 4 mM Mg2+, suggesting RNA as a possible target. However, Hoechst 33258 inhibits growth of Candida strains with and without group I introns. IC50s ranged from 1 to 9 microM for strains with group I introns and were 12 and 32 microM for two strains without group I introns. These studies demonstrate that compounds that bind fungal nucleic acids have the potential to be developed as new therapeutics for Pneumocystis and possibly other fungi, especially if they could be directed to structures that are not present in mammalian cells, such as self-splicing introns.