SGO and the elephant that is still in the room: Wellness, burnout and gynecologic oncology.

OBJECTIVE: To measure wellness and burnout among gynecologic oncology clinicians and identify trends and at-risk populations to inform future interventions. METHODS: Gynecologic oncologist (GO) and advanced practice provider (APP) responses to the 2020 Society of Gynecologic Oncology State of the Society survey were analyzed. The Maslach Burnout Inventory criteria for burnout was used. Work-life balance was scored on a 5-point Likert scale. Chi-square tests were used to compare mental health factors and the prevalence of burnout. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for associations between burnout and gender. RESULTS: 543 survey responses were included for analysis. Most GO (54%) and all APP respondents were female. Female GOs were disproportionately affected by burnout particularly in the Northeast (female(F): 40.9% vs male(M): 19.1%, p = 0.007) and South (F: 42.5% vs M:22.9%, p = 0.01). Burnout in female GOs over 40 was 1.79 (CI: 1.13-2.83; p-value 0.01) times higher than similarly aged males. Females in non-private practice experienced burnout 1.66 times that of males in similar positions (CI: 1.18-2.94; p < 0.0001). Female GOs reported the worst work-life balance across all 5 domains. APPs and female GOs experienced more stress and feeling overwhelmed compared to men. GOs were more reluctant to see a mental health professional (p = 0.0003) or take medication (p = 0.009) than APPs. CONCLUSIONS: Burnout in gynecologic oncology persists in both genders and is felt most acutely by female GOs. APPs are not immune and would benefit from inclusion in future research to mitigate burnout in healthcare clinicians.

Transversus abdominis plane block in robotic gynecologic oncology: a randomized, placebo-controlled trial.

OBJECTIVE: Although robotic surgery decreases pain compared to laparotomy, postoperative pain can be a concern near the site of a larger assistant trocar site. The aim of this study was to determine the efficacy of transversus abdominis plane (TAP) block on 24-hour postoperative opiate use after robotic surgery for gynecologic cancer. METHODS: Sixty-four subjects with gynecologic malignancies who were scheduled to undergo robotic surgery were enrolled into the study. They were randomized to receive a unilateral TAP block to the side of the assistant port via ultrasound guidance. The block was comprised of 30 cc of 0.25% bupivacaine with 3 mcg/mL epinephrine or saline. Opiate use was measured and converted into IV morphine equivalents. Patient-reported pain was measured using the Brief Pain Inventory (BPI) and Visual Analog Scale (VAS). RESULTS: The treatment group used a mean of 64.9 mg morphine in the first 24h compared to 69.3mg for controls (primary outcome, p=0.52). After age-adjustment, the treatment group used a mean of 11.1mg morphine less than controls (p=0.09). Postoperative pain scores assessed by the BPI (6.44 vs. 6.97, p=0.37) and the VAS (3.12 vs. 3.61, p=0.30) were equivalent. Block placement was uncomplicated in 98.4% of participants with mean BMI of 35.3 kg/m(2). Linear regression revealed an approximate 8.1mg decrease in morphine equivalents used per additional decade of life (p=0.0008). There was a positive correlation between the amount of opiates and BMI with an additional 8.8 mg of morphine per 10 kg/m(2) increase in BMI (p=0.0012). CONCLUSIONS: TAP block is safe and feasible in this patient population with a large proportion of morbid obesity. Preoperative TAP block does not significantly decrease opiate use. However; based on these data, a clinically useful nomogram has been created to aid clinicians in postoperative opiate-dosing for patients based on age and BMI.

Outcomes following surgery and adjuvant radiation in stage II endometrial adenocarcinoma.

PURPOSE: To evaluate locoregional control, disease free survival, and overall survival in patients treated with surgery and adjuvant radiation for stage II adenocarcinoma of the endometrium. Secondary goals include identification of prognostic factors and the comparison of toxicity profiles after vaginal cuff brachytherapy (VB) alone or combined with pelvic external beam radiation therapy (EXT). MATERIALS AND METHODS: All patients receiving adjuvant radiation at the University of Wisconsin following surgery for FIGO stage II adenocarcinoma of the endometrium between January 1991 and December 2006 were retrospectively reviewed. RESULTS: Between January 1991 and December 2006, 71 patients with FIGO stage II adenocarcinoma of the endometrium (23 stage IIA, 48 stage IIB) received adjuvant radiation at the University of Wisconsin. Fifty patients were treated with EXT and VB, twenty with VB alone, and one with EXT alone. At a mean follow-up of 5.1 years (range, 0.5-16.8 years), 5-year overall and disease-free survival were both 82%. Factors associated with an increased risk for recurrence include depth of myometrial invasion (p=0.005) and lymphovascular invasion (p=0.02). Receiving EXT was significantly associated with increased depth of myometrial invasion (p=0.007), higher grade (p=0.003), and less extensive surgery (p=0.01). Of the nine recurrences, three were initially local and six were distant recurrences alone. Grade 2 or greater acute and late side effects were significantly greater with EXT therapy compared to VB alone (p<0.0001 and p=0.02, respectively), although severe toxicities (grade 3 or greater) were limited with either modality. DISCUSSION: Local recurrence rates remain low after surgery and adjuvant radiation therapy for stage II endometrial cancer using a combination of VB and EXT tailored to the surgical and pathologic features. VB alone resulted in fewer toxicities without an increased recurrence risk compared to the combination of EXT and VB, suggesting that VB without EXT is sufficient for patients with low-risk histopathologic features and comprehensive surgical staging with complete lymphadenectomy.

Endothelin and the regulation of uteroplacental perfusion in nitric oxide synthase inhibition-induced fetal growth restriction.

The vasoactive mediators nitric oxide and endothelin are both produced in and active in the uterine and placental vasculature. Inhibition of nitric oxide synthase (NOS) results in fetal growth restriction. Endothelin (ET-1) is upregulated in the setting of NOS inhibition. Our purpose was to determine the impact of ET-1 on uterine and placental perfusion in the pregnant rat treated with a NOS inhibitor. Timed-pregnant Sprague-Dawley rats were treated with L-NAME (2.5 mg/kg/h), with and without A-127722 (10 mg/kg/day), or their respective vehicles, for 1, 4, or 7 days beginning on day 14 of gestation. Blood flow to various organs was determined by microsphere infusion. Maternal and fetal plasma nitrate/nitrite (NOx) was determined by fluorometric assay. Uterine and placental perfusion was significantly decreased by NOS inhibition and was restored to normal by ETA antagonism at 1 and 4 days of infusion but not at 7 days. Maternal plasma NOx, but not fetal plasma NOx, was significantly decreased by NOS inhibition alone. ETA antagonism in combination with NOS inhibition significantly lowered fetal plasma NOx. These results indicate that ET-1 is an important regulator of uterine and placental perfusion in the NOS inhibition model of fetal growth restriction. Our results also suggest that maternal administration of L-NAME does not result in significant transport of L-NAME across the placenta, but that addition of an ETA antagonist results in increased placental perfusion, allowing L-NAME greater access to the fetal compartment.

High dose rate (192)Ir afterloading brachytherapy for cancer of the vagina.

We report results of brachytherapy for carcinoma of the vagina, utilizing a Nucletron high dose rate system for Delclos Vaginal Applicators (cylinder) and Syed Template Applicators (interstitial). The linear quadratic (LQ) model was used to determine the optimum time-dose-fractionation schedules. Interstitial doses were determined at the isodose line that included gross tumour. Cylinder doses were determined either at the vaginal surface (5 cases), at 0.5 cm depth (5 cases), or at 1.0 cm depth (1 case). For the first treatment (n=19), interstitial templates were utilized in 8 patients and vaginal cylinders in 11. 11 patients received second treatments: 6 templates and 5 cylinders. The median dose of external beam radiation (n=15) was 40.0 Gy followed, after a median 23 day interval, by high dose rate brachytherapy (HDRB) of 4 fractions in 30-42 h; then a median interval gap of 25 days, followed by repeat HDRB. The median total fractionated HDRB dose per patient was 23.0 Gy (range: 6.9 Gy to 40.4 Gy; calculated low dose rate equivalent of 29.8 Gy). Tumour histologies included 14 squamous cell carcinomas, 2 adenocarcinomas, 2 melanomas, and 1 small cell tumour. Three patients experienced early brachytherapy-related complications (diarrhoea, dysuria and labial dermatitis). Three patients (15.8%) developed serious/late complications including ureteral stenosis, painful vaginal necrosis and small bowel obstruction. The first of these patients received 2 templates, the second a cylinder followed by a template and a cylinder, and the third a single cylinder. The 2 year progression-free survival was 39.3% (median 15.7 months), while the 2 year overall survival was 66.1% (median 29.9 months). (192)Ir afterloading HDRB is a feasible approach to women with vaginal cancer with acceptable toxicity and tumour response. Potential advantages include patient preference, outpatient cost-effectiveness in the case of cylinder technique, and no radiation exposure to hospital personnel. Long-term follow-up is needed to further assess late complications, and larger studies are needed to confirm our results.

Antisense cancer therapy: the state of the science.

Over the last few years, antisense technology has emerged as an exciting and promising strategy in the fight against cancer. The antisense concept is to selectively bind short, modified DNA or RNA molecules to messenger RNA in cells and prevent the synthesis of the encoded protein. As anticancer agents, these molecules can be targeted against a myriad of genes involved in cell transformation, cell survival, metastasis, and angiogenesis. Indeed, the list of possible antisense targets increases as the knowledge of the genetic basis of oncogenesis expands. One aim of this review is to focus on those antisense cancer drugs that have entered human clinical trials. At least four of these compounds are currently in phase II trials, including those targeting protein kinase C-alpha, bcl-2, c-raf, and the R1-alpha subunit of protein kinase A. A new development in antisense chemistry (peptide nucleic acids) is discussed, along with alternative antisense-related strategies (ribozymes and 2-5A-antisense) designed to overcome some of the challenges of this already encouraging technology.

Safety and efficacy of adjuvant single-agent ifosfamide in uterine sarcoma.

PURPOSE: The role of adjuvant therapy for completely resected uterine sarcoma continues to be debated. Previous chemotherapy trials have shown little, if any, advantage over surgery alone, with significant added toxicity. To our knowledge, the current study is the first to evaluate adjuvant ifosfamide in completely resected uterine sarcomas. METHODS: Between 1992 and 1999, 13 consecutive patients with completely resected moderate- to high-grade uterine sarcoma received three cycles of adjuvant ifosfamide (1.5 g/m(2)/day x 3 days, repeated every 28 days). Mesna was given 30 min prior to infusion. Postinfusion mesna was administered to 10 of the patients in the outpatient setting utilizing a subcutaneous infusion pump. The remaining 3 patients received traditional intravenous mesna at 4 and 8 h after infusion. RESULTS: The median follow-up of the patient population was 26 months. For early-stage patients (n = 10), the 2-year progression-free survival was 60%, with a median of 26 months. The 2-year overall survival was 100%, dropping to 67% at 3 years. Early-stage patients showed an advantage in both progression-free and overall survival. Early-stage patients with mixed müllerian tumor (MMT) had a significantly longer time to progression that those with leiomyosarcoma (LMS) (2-year progression-free survival of 100% versus 33%; P = 0.019). Three patients required dose reduction secondary to grade 2-3 toxicities (neutropenia x2, nausea and vomiting x1). All significant toxicity was eliminated with dose reduction. CONCLUSIONS: Adjuvant ifosfamide appears to be safe and well tolerated in patients with completely resected uterine sarcoma. It can easily be given in the outpatient setting if mesna is administered via a subcutaneous pump. Our data, consistent with previous studies in advanced sarcoma, suggest a potentially greater role for ifosfamide in MMT than in LMS.

2-5A antisense directed against telomerase RNA produces apoptosis in ovarian cancer cells.

OBJECTIVE: RNase L is converted to an active form upon binding short 2',5'-oligoadenylates (2-5A). To direct RNase L to an RNA target, 2-5A is attached to an antisense oligonucleotide (2-5A antisense). This chimera can be directed against telomerase-an RNA-protein complex that elongates telomeric DNA and is involved in cellular immortalization. Our objective is to investigate the effect of 2-5A antisense by targeting telomerase RNA (hTR) in the ovarian cancer cell line, HEY-1B. METHODS: Baseline RNase L levels and telomerase activities were measured in both HEY-1B and normal ovarian epithelial cells (NOE). Cells were treated daily with chimeric oligonuclotides (ODN) directed against four different hTR sites, or control ODNs including nonchimeric antisense, 2-5A fused to a mismatched sequence, or inactive 2-5A fused to antisense. At 48 h, apoptosis was evaluated using the TUNEL assay. After six daily ODN administrations, telomerase activity was redetermined, and at 7 days viability counts were obtained. RESULTS: Both cell lines expressed similar levels of RNase L. Hey-1B displayed telomerase activity while NOE did not. After 7 days of transfection, 2-5A antisense ODNs caused profound cell death in the HEY-1B cells, but not in the NOE cells. This effect was seen regardless of hTR target site, and ODN controls showed no significant decrease in cell viability in either cell line. HEY1B cells treated with 2-5A antisense against hTR showed a decrease in telomerase activity and a profound induction of programmed cell death. CONCLUSIONS: The results suggest that 2-5A antisense directed against telomerase RNA results in apoptotic cell death in ovarian cancer cells, but not normal ovarian epithelial cells. The 2-5A antisense strategy may hold a considerable advantage over the conventional antisense approach in targeting cancer-causing genes.

Ovarian carcinoma metastatic to the choroid of the eye.

A case of papillary serous ovarian adenocarcinoma with choroidal metastasis to the eye is reported. Central nervous system metastasis of any kind is rare from this tumor, and only three cases of choroidal metastases have been reported to date. A 67-year-old women presented 2 years after diagnosis of Stage IIIC papillary serous ovarian adenocarcinoma with complaints of a "teardrop"-shaped visual field defect in her right eye. Fundoscopic examination revealed metastasis to the superior-temporal right choroid. No coexisting sites of recurrence were discovered. This case highlights the need to thoroughly and promptly investigate the etiology of visual field complaints in patients with a history of ovarian cancer.

Endometrial adenocarcinoma metastatic to the scalp: case report and literature review.

A rare case of scalp metastasis from endometrial adenocarcinoma, demonstrating the poor prognosis for these patients, is reported. A 56-year-old woman with FIGO Stage IC, Grade 1 endometrial adenocarcinoma presented 15 months after initial surgery and radiation therapy with a scalp metastasis. Metastatic evaluation revealed widespread extrapelvic disease. She did not respond to chemotherapy and died 3 months after recurrence. Her course typifies that of patients with other cutaneous metastases as described in the literature: disease noted elsewhere at the time of recurrence, poor response to therapy, and death within 6 months.

Total hip replacement and other orthopedic hip procedures.

The history of total hip replacement including that of the Girdlestone procedure and resurfacing procedures is discussed. An overview of total hip replacement and its indications and complications forms the bulk of this section. Also, the use of porous-coated prostheses and endoprostheses as well as pins and plates is discussed and illustrated.

Carpal instability in rheumatoid arthritis.

The authors examined prospectively the prevalence of and relations among patterns of carpal instability in 52 patients with proven rheumatoid arthritis. Posteroanterior, lateral and oblique radiographs of both wrists were obtained. Nineteen patients exhibited one or more patterns of instability. The most common isolated pattern was volar intercalated segmental instability, apparent in six patients. Five patients showed more than one pattern, most commonly a combination of ulnar translocation and volar carpal subluxation. Patients with active erosions or changes in the distal radioulnar joint were more likely to exhibit instability than those without such findings. Carpal instability is a frequent mechanical complication of rheumatoid arthritis. The radiologist should be aware of this possibility, so that a diagnosis can be made promptly and appropriate clinical management begun.