Cost-effectiveness of BRCA1 testing at time of obstetrical prenatal carrier screening for cancer prevention.

BACKGROUND: Improved technologies paired with an increase in access to genetic testing have led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time when precancer screening, chemoprevention, and/or risk-reducing surgery may be beneficial. OBJECTIVE: This study aimed to inform clinical decision-making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective. STUDY DESIGN: A decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years were used to simulate the lifespan of patients. The setting was obstetrical clinics in the United States, and the participants were a theoretical cohort of 1,429,074 pregnant patients who annually underwent expanded carrier screening. RESULTS: Among our cohort, BRCA1 testing resulted in the identification of an additional 3716 BRCA1-positive patients, the prevention of 1394 breast and ovarian cancer cases, and 1084 fewer deaths. BRCA1 testing was a cost-effective strategy compared with no BRCA1 testing with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life years. In a 1-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0.00% to 20.00% and found that BRCA1 testing continued to be the cost-effective strategy until the prevalence rate was reduced to 0.16%. Multiple additional sensitivity analyses did not substantially affect the cost-effectiveness. CONCLUSION: The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing.

Revisional Techniques for Secondary Cleft Lip Deformities.

Secondary deformities of repaired cleft lips are an unfortunate complication despite the meticulous approach of modern primary procedures. Most of these surgeries take place in the patient's early life and must be strategically planned to provide optimal cosmesis with minimal interventions. Depending on the level of severity, treatment of the secondary deformities ranges from noninvasive or minimally invasive techniques to complete revision cheiloplasty. Many novel topical, injectable, and laser therapies have allotted physicians more technical flexibility in treating superficial distortions. Nonetheless, surgical techniques such as diamond excision and adjacent tissue transfer remain popular and useful reconstructive modalities. Deformities involving the orbicularis oris must be completely taken down to allow full access to the muscle. Complete revision cheiloplasty requires recreation of the cleft defect and reconstruction similar to the primary repair. Due to the myriad of presentations of these secondary deformities, familiarity with the various treatments available is imperative for any cleft surgeon.

Revision Peripheral Nerve Surgery of the Upper Extremity.

Peripheral nerve injuries of the upper extremity can result from a wide array of etiologies, with the two most common being compression neuropathy and traumatic injuries. These types of injuries are common and can be psychologically, functionally, and financially devastating to the patient. A detailed preoperative evaluation is imperative for appropriate management. Traumatic injuries can typically be treated with local burial techniques, targeted muscle reinnervation, and regenerative peripheral nerve interfaces. Median nerve compression is frequently managed with complete release of the antebrachial fascia/transverse carpal ligament and/or use of flap coverage such as the hypothenar fat pad flap and local muscle flaps. Ulnar nerve compression is commonly managed via submuscular transposition, subcutaneous transposition, neurolysis, and nerve wrapping. In this review, we discuss the preoperative evaluation, surgical techniques, and advantages and disadvantages of each treatment modality for patients with compressive and traumatic upper extremity nerve injuries.

Scar Revisions.

Scars pose a complex challenge to the reconstructive surgeon in the variability of their presentation and their effect on cosmesis and function. Numerous surgical and nonsurgical options exist for scar management, each with their respective advantages and disadvantages. Each treatment modality should be tailored to the patient to ensure enhanced outcomes. In this review, we discuss different scar presentations, scar management options, and the benefits and risks with undergoing these various treatment modalities.

Reconstructing Severe Lower Extremity Skin Necrosis in a Pediatric Patient.

ABSTRACT: Purpura fulminans can result in significant full-thickness wounds, posing a challenge in the pediatric population, given the paucity of donor sites for reconstruction. The authors present the case of an 11-month-old patient for whom a split-thickness skin allograft (TheraSkin) was successfully implemented as a temporizing measure for a large leg wound.

Distraction Osteogenesis: Mandible and Maxilla.

Mandibular and maxillary deformities commonly require surgical intervention. Prior to distraction osteogenesis, traditional modalities involving single-staged translocation and rigid fixation were used to correct these craniofacial anomalies. Distraction osteogenesis has evolved as a compelling alternative for treating aesthetic and functional dentofacial defects. The process of distraction osteogenesis involves three phases-latency, activation, and consolidation-which allow for appropriate translation of the affected craniofacial skeleton. This review will cover the role of distraction for managing congenital and acquired deformities of the mandible and maxilla. This novel technique can be performed at numerous anatomical sites along the craniofacial skeleton to treat a variety of anomalies, which serves as a testament to its adaptability and efficacy. Importantly, distraction osteogenesis also has the ability to simultaneously increase bone length and the overlying soft tissue envelope. This advantage results in larger advancements with reduced relapse rates and improved patient satisfaction. While complications remain a concern, it stands to reason that the measurable benefits observed underscore the power and versatility of distraction osteogenesis.

Pediatric Fronto-Orbital Skull Reconstruction.

Craniofacial surgery in children is a highly challenging discipline that requires extensive knowledge of craniofacial anatomy and pathology. Insults to the fronto-orbital skeleton have the potential to inflict significant morbidity and even mortality in patients due to its proximity to the central nervous system. In addition, significant aesthetic and ophthalmologic disturbances frequently accompany these insults. Craniosynostosis, facial trauma, and craniofacial tumors are all pathologies that frequently affect the fronto-orbital region of the craniofacial skeleton in children. While the mechanisms of these pathologies vary greatly, the underlying principles of reconstruction remain the same. Despite the limited data in certain areas of fronto-orbital reconstruction in children, significant innovations have greatly improved its safety and efficacy. It is imperative that further investigations of fronto-orbital reconstruction are undertaken so that craniofacial surgeons may provide optimal care for these patients.

Treatment of Non-melanoma Skin Cancers in the Absence of Mohs Micrographic Surgery.

Non-melanoma skin cancers are the most common malignancies globally. Although non-melanoma skin cancers exhibit low metastatic potential, they can be locally destructive, necessitating complex excisions and reconstructions. Mohs micrographic surgery is the gold-standard treatment for high-risk non-melanoma skin cancers in patients who are appropriate surgical candidates. Despite its efficacy, Mohs micrographic surgery is not readily available in most geographic regions, necessitating that plastic surgeons be well-versed in alternative treatment modalities for non-melanoma skin cancer. Herein, we will discuss the management of non-melanoma skin cancers in settings where Mohs micrographic surgery is not readily available.

Necessity of routine cardiac evaluation in patients receiving pegylated liposomal doxorubicin for gynecologic cancer.

OBJECTIVE: Pegylated liposomal doxorubicin (PLD) has similar reported clinical efficacy compared with conventional doxorubicin with less cardiotoxicity. The manufacturer of PLD advises that cardiac function should be evaluated with endomyocardial biopsy, echocardiography or multigated radionucleotide scan (MUGA) pre-treatment and during therapy. This study was designed to assess the necessity of pre-treatment cardiac evaluation in patients receiving PLD. METHODS: After IRB approval, a retrospective study of all women with gynecologic cancer who received PLD from 2006 to 2018 was performed. Demographic information, treatment records, cardiac risk factors, and cardiac surveillance testing were examined. Wilcoxon signed rank sum test and logistic regression were used to evaluate the association of cumulative PLD exposure with cardiotoxicity. RESULTS: A total of 235 patients received PLD for gynecologic cancer. Patients received a median of 3 cycles of PLD with a cumulative dosage of 237 mg over a median follow-up time of 24 months. Sixteen patients in the cohort (7%) had no cardiac surveillance at all. Of the remaining patients who underwent cardiac testing, 183 (84%) received MUGA scans and 36 (16%) had echocardiography. Of the 56 patients who had both pre- and post-treatment cardiac testing, there was no significant difference in median ejection fraction (p = 0.17). Three patients developed PLD-associated cardiac toxicity but only one patient had severe manifestations requiring discontinuation of PLD therapy. CONCLUSIONS: Routine cardiac testing before, during or after treatment with PLD may be unnecessary. Cardiac testing may be more appropriate for individual patients for whom the clinical suspicion of PLD-related cardiac toxicity is high.

Utilizing the Patient Reported Outcomes Measurement Information System (PROMIS®) to increase referral to ancillary support services for severely symptomatic patients with gynecologic cancer.

OBJECTIVE: The Patient-Reported Outcomes Measurement Information System (PROMIS®) Network has developed a comprehensive repository of electronic patient reported outcomes measures (ePROs) of major symptom domains that have been validated in cancer patients. Their use for patients with gynecologic cancer has been understudied. Our objective was to establish feasibility and acceptability of PROMIS ePRO integration in a gynecologic oncology outpatient clinic and assess if it can help identify severely symptomatic patients and increase referral to supportive services. METHODS: English-speaking patients with a confirmed history of gynecologic cancer completed PROMIS ePROs on iPads in the waiting area of an outpatient gynecologic oncology clinic. Symptom scores were calculated for each respondent and grouped using documented severity thresholds. Response data was compared with clinicopathologic characteristics across symptom domains. Severely symptomatic patients were offered referral to ancillary services and asked to complete post-exposure surveys assessing acceptability of the ePRO. RESULTS: Of the 336 patients who completed ePROs, 35% had active disease and 19% had experienced at least one disease recurrence. Sixty-nine percent of the cohort demonstrated moderate to severe physical dysfunction (60%), pain (36%), fatigue (28%), anxiety (9%), depression (8%), and sexual dysfunction (32%). Thirty-nine (12%) severely symptomatic patients were referred to services such as psychiatry, palliative care, pain management, social work or integrative oncology care. Most survey respondents identified the ePROs as helpful (78%) and easy to complete (92%). CONCLUSIONS: Outpatient PROMIS ePRO administration is feasible and acceptable to gynecologic oncology patients and can help identify severely symptomatic patients for referral to ancillary support services.

Characterization of Risk Factors and Timing of Venous Thromboembolism in Patients With Uterine Serous Carcinoma.

OBJECTIVE: To characterize risk factors and timing of venous thromboembolism in women with uterine serous carcinoma. METHODS: A retrospective cohort study was performed including all women diagnosed with uterine serous carcinoma from 1999 to 2016 at our institution. Clinicopathologic data and information regarding timing of venous thromboembolism were abstracted from the medical record. Logistic regression and Cox proportional hazards modeling were used to examine the association between covariates and risk and timing of venous thromboembolism. RESULTS: Seventy of the 413 included patients (17%) developed venous thromboembolism, with a median time from presentation to venous thromboembolism of 7.2 months (interquartile range 1.0-24.8) and from surgery to venous thromboembolism of 13.2 months (interquartile range 3.5-33.6). Fifty-nine of the 70 patients (84%) who developed venous thromboembolism were diagnosed either before surgery or greater than 6 weeks postoperatively. Twenty-two of the 70 patients (31%) who developed clots were on chemotherapy at the time of diagnosis. Venous thromboembolism was highly associated with cancer stage and presence of hypertension (P<.01). Cox proportional hazards modeling revealed that only cancer stages III and IV (hazard ratio [HR] 3.20, 95% CI 1.54-6.64 and HR 8.68, 95% CI 4.50-16.73, respectively) and hypertensive or cardiovascular diseases (HR 2.29, 95% CI 1.08-4.85 and HR 1.82, 95% CI 1.05-3.13) were associated with time to venous thromboembolism. CONCLUSION: Patients with uterine serous carcinoma are at high risk of developing venous thromboembolism even many months after their cancer diagnosis. This study generates the hypothesis that venous thromboembolism prophylaxis may be beneficial in patients with uterine serous carcinoma during other time points along the continuum of disease rather than only in the postoperative period, especially for those with advanced cancer.

Setting Benchmarks for the New User: Training on the Robotic Simulator.

BACKGROUND AND OBJECTIVES: Data showing the impact of the robotic simulator on fellowship training are limited. This study was conducted to determine whether simulator scores reflect the experience of the robotic gynecologic surgeon and to develop a simulator curriculum for trainees in gynecologic oncology. METHODS: All faculty and fellows in the Department of Gynecologic Oncology and Reproductive Medicine were asked to participate. For phase 1, all participants were divided into 2 groups based on robotic surgical experience: beginner (0-50 cases) and experienced (>50 cases). Each participant completed 9 modules 3 times each to establish baseline data. Median module scores for the experienced group defined the benchmarks scores. In phase 2, all trainees who did not meet the benchmark score on a module were asked to repeat the module until they reached the score twice. RESULTS: Twenty-four participants were included: 18 beginners and 6 experienced surgeons. For all modules, experienced surgeons received higher median scores than beginners. There was a significant difference between the scores of the 2 groups in the Energy Switching 1 (87.5 vs 92.5; P = .002) and Suture Sponge 2 (75.0 vs 87.3; P = .011) modules. Thirteen trainees participated in phase 2. For 8 of 9 of the modules, >75% of trainees met proficiency, with a median of 3 to 6 attempts (range, 2-24). CONCLUSION: Based on the findings, scores reflected each surgeon's experience. With repetition, most of the trainees were able to reach the benchmark scores. Further study is needed to determine the impact of surgical simulation on true intraoperative performance.

The gynecologic oncology fellowship interview process: Challenges and potential areas for improvement.

The application and interview process for gynecologic oncology fellowship is highly competitive, time-consuming and expensive for applicants. We conducted a survey of successfully matched gynecologic oncology fellowship applicants to assess problems associated with the interview process and identify areas for improvement. All Society of Gynecologic Oncology (SGO) list-serve members who have participated in the match program for gynecologic oncology fellowship were asked to complete an online survey regarding the interview process. Linear regression modeling was used to examine association between year of match, number of programs applied to, cost incurred, and overall satisfaction. Two hundred and sixty-nine eligible participants reported applying to a mean of 20 programs [range 1-45] and were offered a mean of 14 interviews [range 1-43]. They spent an average of $6000 [$0-25,000], using personal savings (54%), credit cards (50%), family support (12%) or personal loans (3%). Seventy percent of respondents identified the match as fair, and 93% were satisfied. Interviewees spent a mean of 15 [0-45] days away from work and 37% reported difficulty arranging coverage. Linear regression showed an increase in number of programs applied to and cost per applicant over time (p < 0.001) between 1993 and 2016. Applicants who applied to all available programs spent more (p < 0.001) than those who applied to programs based on their location or quality. The current fellowship match was identified as fair and satisfying by most respondents despite being time consuming and expensive. Suggested alternative options included clustering interviews geographically or conducting preliminary interviews at the SGO Annual Meeting.

Laparoscopic hysterectomy with morcellation for a suspected uterine fibroid resulting in dissemination of cervical adenocarcinoma: A case report.

•Morcellation of an undetected cervical cancer could be avoided with appropriate screening.•Morcellation of an unknown cervical cancer may impact a patient's survival.

Effect of modified starch and nanoclay particles on biodegradability and mechanical properties of cross-linked poly lactic acid.

Mechanical properties and biodegradation of cross-linked poly(lactic acid) (PLA)/maleated thermoplastic starch (MTPS)/montmorillonite (MMT) nanocomposite were studied. Crosslinking was carried out by adding di-cumyl peroxide (DCP) in the presence of triallyl isocyanurate (TAIC) as coagent. At first, MTPS was prepared by grafting maleic anhydride (MA) to thermoplastic starch in internal mixer. Experimental design was performed by using Box-Behnken method at three variables: MTPS, nanoclay and TAIC at three levels. Results showed that increasing TAIC amount substantially increased the gel fraction, enhanced tensile strength, and caused a decrease in elongation at break. Biodegradation was prevented by increasing TAIC amount in nanocomposite. Increasing MTPS amount caused a slight increase in gel fraction and decreased the tensile strength of nanocomposite. Also, MTPS could increase the elongation at break of nanocomposite and improve the biodegradation. Nanoclay had no effect on the gel fraction, but it improved tensile strength.

Oropharyngeal squamous cell carcinoma in the veteran population: Association with traditional carcinogen exposure and poor clinical outcomes.

BACKGROUND: A significant fraction of oropharyngeal squamous cell carcinoma (SCC) cases is associated with traditional carcinogens; in these patients, treatment response and clinical outcomes remain poor. METHODS: We evaluated patient, tumor, and treatment characteristics for 200 veterans with oropharyngeal SCC treated at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) between 2000 and 2012. RESULTS: Most patients (77%) were white and heavy smokers. Twenty-seven patients required tracheostomy and 63 required gastrostomy placement during treatment. Overall survival (OS) at 5 years was 40%. Survival was impacted by T classification, treatment intensity, completion of treatment, and p16 tumor status. Almost 30% of patients were unable to complete a treatment regimen consistent with National Comprehensive Cancer Network (NCCN) guidelines. CONCLUSION: Oropharyngeal SCC in veterans is associated with traditional carcinogens and poor clinical outcomes. Despite heavy smoking exposure, p16 tumor status significantly impacts survival. Careful consideration must be given to improving treatment paradigms for this cohort given their limited tolerance for treatment escalation.