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BackgroundWith radiotherapy having entered the era of image guidance, or image‐guided radiation therapy (IGRT), imaging procedures are routinely performed for patient positioning and target localization. The imaging dose delivered may result in excessive dose to sensitive organs and potentially increase the chance of secondary cancers and, therefore, needs to be managed.AimsThis task group was charged with: a) providing an overview on imaging dose, including megavoltage electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR), Tomotherapy MV‐CT, megavoltage cone‐beam CT (MV‐CBCT) and kilovoltage cone‐beam CT (kV‐CBCT), and b) providing general guidelines for commissioning dose calculation methods and managing imaging dose to patients.Materials & MethodsWe briefly review the dose to radiotherapy (RT) patients resulting from different image guidance procedures and list typical organ doses resulting from MV and kV image acquisition procedures.ResultsWe provide recommendations for managing the imaging dose, including different methods for its calculation, and techniques for reducing it. The recommended threshold beyond which imaging dose should be considered in the treatment planning process is 5% of the therapeutic target dose.DiscussionAlthough the imaging dose resulting from current kV acquisition procedures is generally below this threshold, the ALARA principle should always be applied in practice. Medical physicists should make radiation oncologists aware of the imaging doses delivered to patients under their care.ConclusionBalancing ALARA with the requirement for effective target localization requires that imaging dose be managed based on the consideration of weighing risks and benefits to the patient.

BACKGROUND: OB/GYN residencies use myTIPreport to improve resident feedback. Validation is viewed as a process with construct validity established from different levels of evidence. In Kane's validity framework, extrapolation focuses on links between assessment outcomes and other measures of performance. METHODS: Single-institution, prospective cohort study of OB/GYN residents (n=24). Using the ACGME case log system and myTIPreport application, associations of PGY level, number of previous hysteroscopies (HSC), total vaginal hysterectomies (TVH), and total abdominal hysterectomies (TAH) with myTIPreport ratings of each procedure when performed in the operating room were assessed using Spearman's test correlation. A pilot study of inexpensive, low technology simulation models was initiated to assess extrapolation evidence for myTIPreport in the simulation setting (n=8). RESULTS: Associations (P<.01) existed between PGY level and myTIPreport scores in the OR (r=0.612 for HSC, r=0.763 for TAH, r=0.864 for TVH). Associations (P<.01) existed between number of procedures performed and myTIPreport scores in the OR (r=0.587 for HSC, r=0.681 for TAH, r=0.869 for TVH). An association (r=0.852, P=.031) existed between number of TVHs performed in the OR and myTIPreport scores during simulation, but not for TAH (P=.199) nor HSC (P=.154) due to the small sample size. DISCUSSION: The association between myTIPreport TVH performance with PGY level and number of TVHs was the strongest, supporting extrapolation evidence. The associations were weaker for TAH and HSC in both the OR and simulation settings secondary to higher ratings for lower PGY levels and fewer cases.

INTRODUCTION: Female patients being evaluated for liver transplantation (LT) routinely undergo a gynecologic exam including cervical cancer screening. The prevalence of cervical cytologic abnormalities in this high risk population is unknown. Our study determines prevalence of cervical cytologic abnormalities, HPV positive status, and risk factors for abnormal cervical screening for this population. METHODS: With Institutional review board approval, we reviewed 375 charts of women undergoing evaluation for LT from 2008‒2013 at Mayo Clinic Florida. We recorded demographics, Pap smear results, High risk HPV positive results, and co-morbid conditions. Univariate analysis was done to determine risk factors. We compared the result of the LT group to the general female population getting cervical cancer screening during the same time period. RESULTS: 37 of 375 (9.86%) LT patients had abnormal Pap smear, compared to 1784 of 26118 (6.83%) of the general population patients (p < 0.01). Among LT patients with cervical cytologic abnormalities, 40.5% were ASCUS, HPV positive (64.8% for non-LT patients), 29.7% were LSIL (28.1% for non-LT patients), 5.4% were HSIL (6.7% for non-LT patients) and 24.3% were cytology negative with HPV positive (0.2% for non-LT patients, p < 0.05). Younger age and presence of hypertension were associated with higher risk of having an abnormal cervical cytology or positive HPV status among LT patients. CONCLUSION: Patients undergoing evaluation for LT have increased prevalence of abnormal cervical cytology, or a positive High risk HPV test. Gynecologic surveillance for this high risk population is recommended.

Abstract Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case–control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A&gt;C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G&gt;A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G&gt;A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G&gt;T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789–99. ©2017 AACR.

BackgroundAutomated external defibrillators can provide life‐saving therapies to treat ventricular fibrillation. We developed a prototype unit that can deliver a unique shock waveform produced by four independent capacitors that is delivered through two shock vectors, with the rationale of providing more robust shock pathways during emergent defibrillation. We describe the initial testing and feasibility of this unique defibrillation unit, features of which may enable downsizing of current defibrillator devices.MethodsWe tested our defibrillation unit in four large animal models (two canine and two swine) under general anesthesia. Experimental defibrillation thresholds (DFT) were obtained by delivery of a unique waveform shock pulse via a dual‐vector pathway with four defibrillation pads (placed across the chest). DFTs were measured and compared with those of a commercially available biphasic defibrillator (Zoll M series, Zoll Medical, Chelmsford, MA, USA) tested in two different vectors. Shocks were delivered after 10 seconds of stable ventricular fibrillation and the output characteristics and shock outcome recorded. Each defibrillation series used a step‐down to failure protocol to define the defibrillation threshold.ResultsA total of 96 shocks were delivered during ventricular fibrillation in four large animals. In comparison to the Zoll M series, which delivered a single‐vector, biphasic shock, the energy required for successful defibrillation using the unique dual‐vector biphasic waveform did not differ significantly (P = 0.65).ConclusionsOur early findings support the feasibility of a unique external defibrillation unit using a dual‐vector biphasic waveform approach. This warrants further study to leverage this unique concept and work toward a miniaturized, portable shock delivery system.

Steroid cell tumor not otherwise specified (NOS) is a rare subtype of sex cord stromal tumor of the ovary and contributes less than 0.1% of all ovarian neoplasms. The majority of tumors occur in pre-menopausal women (mean age: 43 years), in which 56-77% of patients present with virilization due to excess testosterone. An 80-year-old woman with worsening alopecia and excessive growth of coarse hair on abdomen and genital area was found to have elevated serum testosterone level (462 ng/mL). Radiologic studies were consistent with bilateral adrenal adenomas. Bilateral adrenal venous sampling ruled out the adrenal gland as origin of hormone secretion. A diagnostic and therapeutic bilateral salpingo-oophorectomy confirmed steroid cell tumor NOS of the left ovary. Post-operatively, the patient had complete resolution of her symptoms and normalization of testosterone level. Our case emphasizes the importance of a clinical suspicion for an occult testosterone secreting ovarian tumor in a symptomatic patient without obvious ovarian mass on imaging.

Abstract Dihydropyrimidine dehydrogenase (DPD) is a major determinant of the efficacy and toxicity of 5-fluorouracil in various cancer therapies. Single nucleotide polymorphisms (SNPs) within DPYD have been studied extensively for years. However, known SNPs do not explain most cases of altered DPD activity and response to 5-FU. Furthermore, variations of DPYD expression in cancer patients have been reported; however, the underlying molecular mechanism is unclear. This suggests that regulation of DPYD expression may be an additional mechanism to control DPD activity. In this study, we focused on epigenetic regulation of DPD and specifically investigated the role of histone methylation on DPYD expression. Inhibition of the H3K27 methyl-transferase Ezh2 by either GSK-126 or a dominant-negative histone H3 mutant significantly increased DPYD expression in various cell lines. The expression of thymidylate synthetase, a major target of 5-fluorouracil toxicity, was not altered. Consistent with elevated DPYD expression, cells that lost H3K27me3 were more resistant to 5-fluorouracil. Furthermore, we demonstrated that Ezh2 and H3K27me3 were enriched on the promoter and the first exon of DPYD in low-DPD expressing cells, but not in cell lines with high DPD levels. Additionally, the enrichment of H3K27me3 on the DPYD promoter was negatively correlated with cellular DPD activity in peripheral mononuclear cells from healthy volunteers. Finally, CRISPR/Cas9-mediated targeting of Ezh2 to the DPYD promoter artificially increased H3K27me3 and suppressed DPYD expression. Collectively, these data suggest that histone methylation can regulate DPYD expression, providing a previously unrecognized mechanism of 5-fluorouracil sensitivity. The tri-methylation of H3K27 is a potential biomarker for guiding individualized 5-FU therapy. Citation Format: Rentian Wu, Steven Offer, Calvin Jerde, Garrett Dunlap, Robert Diasio. Histone H3K27 tri-methylation regulates DPYD expression and cellular sensitivity of 5-fluorouracil. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr B49.

Although studies on simulation of rare complications have become more common in the trauma and obstetric literature, there is a paucity of studies on simulation of rare laparoscopic emergencies. High-fidelity models, virtual reality systems, and porcine labs are available; however, their cost limits wider use and repetition of skills. A low-cost, laparoscopic entry and emergency model was created using on-hand base parts. A convenience sample of obstetrics/gynecology and general surgery residents and attending surgeons completed a laparoscopic entry and emergency scenario using an innovative model in the multidisciplinary simulation center. A total of 29 gynecology, urology, and general surgery residents, fellows, and attending surgeons participated in the laparoscopic emergency simulation drill. Of the 29 participants of the laparoscopic emergency simulation drill using the model, 27 (93.1%) agreed or strongly agreed that the simulated drill approximates the stress of a vascular injury during laparoscopy and 27 (93.1%) agreed or strongly agreed that the model set up appears appropriate for approximating a retroperitoneal hematoma. The reusable, laparoscopic simulation model and emergency drill were rated favorably by participants. The model and drill have the potential to be used for multidisciplinary drills that include anesthesiologists, surgical nurses, surgical technologists, and surgeons.