Epidemiology of limb trauma interventions in France: Current state and future projections.

CONTEXT: The distributions and projections of trauma, treated according to the anatomical region, have not been studied in France. The objectives of this study were to obtain French epidemiological data specific to trauma procedures in orthopedic surgery, as well as to establish a statistical trend on the evolution of medical and surgical procedures resulting from this, since 2013 and over the years to come. Our hypothesis was that an increasing trend in trauma procedures since 2013 exists, with an epidemiological forecast of a continuing increase over 50 years, mainly in the context of the management of osteoporotic fractures related to the ageing French population. MATERIAL AND METHODS: We conducted a retrospective study using national data to obtain completion of procedures between the start of 2013 and the end of 2021. RESULTS: From 2013 to 2021, we noted a total of 5,216,567 procedures related to orthopedic traumatology for an average of 579,618 procedures per year. We noted an overall increase in all procedures, continuing from 2013 to 2019, with an average annual increase of 1.125%. The most commonly performed procedure was osteosynthesis, with an average of 276,989 procedures per year. This was followed by wound sutures with an average of 185,023 procedures, orthopedic reductions of fractures and/or dislocations at an average of 62,960, then arthroplasties with 25,425 procedures per year, musculotendinous ruptures were 19,755 procedures per year, surgical reductions of fractures and/or dislocations represented 6920 procedures per year, and fasciotomies with 2848 procedures. From 2013 to 2021, there was an annual average of 276,989 osteosynthesis procedures. Open osteosynthesis, with an average of 146,547 procedures per year, represented 55% of osteosynthesis procedures. Fractures of the proximal end of the femur represented 79,549 procedures on average per year, including 46,621 (58%) involving the trochanter, while 32,852 (41%) were of the femoral neck. Wrist fractures accounted for an annual average of 55,300. Hand fractures represented an annual average of 38,444, of which 52.2% were closed (17,778). On average, 1000 fractures per year involved the carpus without scaphoid involvement, and 2177 scaphoid fractures. Ankle fractures represented 37,951 procedures on average per year, including 74% of the malleolar complex (28,199). Leg fractures represented 17,613 procedures per year, 58% tibial diaphysis (10,091), 41% tibial plateau (6,857). The strengths of this study are the exhaustiveness of the data, presenting all the Common Classification of Medical Procedures (CCAM) chosen during the defined period. CONCLUSION: This study allowed us to establish, to our knowledge, the first epidemiological database of French orthopedic traumatology. LEVEL OF EVIDENCE: IV; epidemiological descriptive study.

Partial-Length Treatment With Brachytherapy in Patients With Endometrial Cancer With High-Risk Features Is as Effective as Full-Length Vaginal Brachytherapy but With Reduced Toxicity.

PURPOSE: Full-length vaginal (FLV) brachytherapy for patients with endometrial cancer and high-risk features should be considered as per the American Brachytherapy Society to reduce distal vaginal recurrence in patients with endometrial cancers with papillary serous/clear cell histologies, grade 3 status, or extensive lymphovascular invasion. We sought to investigate this patient population and report outcomes of treatment with high-dose-rate (HDR) brachytherapy in women treated with FLV brachytherapy versus partial-length vaginal (PLV) brachytherapy. METHODS AND MATERIALS: With institutional review board approval, we identified patients with endometrial cancer meeting American Brachytherapy Society criteria of high-risk features treated with adjuvant HDR between 2004 and 2010. HDR doses were 21Gy in 3 fractions delivered to either the full-length or partial-length vagina. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group scale and Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer grading, respectfully. Vaginal recurrences were assessed by physical examination and pap smears. Statistical analyses were performed using SPSS version 23 software. RESULTS: Of 240 patients treated with HDR brachytherapy, 121 were treated with FLV brachytherapy, and 119, with PLV brachytherapy. The median follow-up was 9.5 years (range, 8-11 years) for FLV patients and 8.5 years (range, 7-10 years) for PLV patients; 0% of patients had vaginal recurrences, and 1.4% and 0.9% had proximal vaginal recurrences, respectively (P = .54). All patients treated with FLV brachytherapy developed grade 3 mucositis of the lower vagina/introitus (P < .0001) and had increased analgesics use compared with those treated with PLV brachytherapy (P < .0001). In total, 23% of patients treated with FLV brachytherapy developed grade 3 stenosis of the lower vagina/introitus, in contrast to 0% of patients treated with PLV brachytherapy (P < .0001). CONCLUSIONS: PLV brachytherapy is as effective as FLV brachytherapy in reducing local recurrence and causes a significantly lower incidence of acute and late toxicities. The results of this study caution radiation oncologists regarding the careful use of FLV brachytherapy in patients with endometrial cancer and high-risk features.

Male nursing students' experiences during prelicensure education: An integrative review.

BACKGROUND: Males represent less than 10 % of the global nursing workforce. To increase the recruitment and representation of male nurses, their experiences in prelicensure nursing education must be understood. OBJECTIVES: The purpose of this integrative review was to explore literature related to male nursing students' experiences during prelicensure education. DESIGN: An integrative review of the literature was conducted using Whittemore and Knafl's methodology. DATA SOURCES: Database searches of CINAHL, PubMed, ERIC, Emcare, and Scopus were conducted. REVIEW METHODS: Database searches identified 237 articles for initial review. Titles, abstracts, and full-text articles were screened for relevance. Quality appraisal was evaluated using the Mixed Methods Appraisal Tool Version 2018. Data analysis was conducted using Conventional Content Analysis. RESULTS: Twenty-two articles (19 qualitative, two quantitative, and one mixed-methods) were included in this review. The existing literature suggests that male nursing students have generally negative experiences during their prelicensure education due to external reactions from family, friends, peers, and healthcare providers to their choice of nursing as a profession; lack of male role models; extensive assistance with physical tasks in the clinical setting; exclusion in obstetrics clinical experiences; and female-gendered descriptions of nurses within the educational environment. Fostering new relationships was identified as a positive experience during prelicensure education. CONCLUSIONS: Generally, male nursing students have negative experiences during their prelicensure education, with limited positive experiences. As such, nurse educators should implement strategies, such as avoiding gendered references when referring to the nurse, offering male mentorship when possible, and providing comparable clinical assignments to students regardless of gender, to improve male nursing students' experiences in prelicensure education and, consequently, increase the recruitment and retention of men into the nursing profession. Future research is needed to more comprehensively understand male nursing students' experiences during prelicensure education and the impact of teaching strategies on their experiences.

Surveillance Only for High-risk FIGO Stage IA/IB Malignant Ovarian Germ Cell Tumors: Results From a National Cancer Database.

OBJECTIVES: Investigate the use and outcomes of a surveillance only strategy for patients with high-risk stage I malignant ovarian germ cell tumors. METHODS: Patients with International Federation of Gynecology and Obstetrics stage IA/IB grade 2 or 3 immature teratoma, yolk sac, or mixed germ cell tumor diagnosed between 2004 and 2014 who had at least 1 month of follow-up were drawn from the National Cancer Database. Overall survival (OS) was evaluated for each histologic subtype using Kaplan-Meier curves, and compared with the log-rank test. RESULTS: A total of 497 patients were identified; 115 (23.1%) with grade 2 immature teratoma, 157 (31.6%) with grade 3 immature teratoma, 101 (20.3%) with yolk sac tumor, 124 (25%) with mixed germ cell tumor. Rate of adjuvant chemotherapy was 68.2% (655 patients), while rate of lymph node biopsy/dissection was 55.2%. A total of 19 (3.8%) deaths were observed at a median of 29.8 months. There was no difference in OS between patients who did and did not receive adjuvant chemotherapy with grade 2 (P=0.35) and grade 3 immature teratoma (P=0.47) or mixed germ cell tumors (P=0.55). Patients with yolk sac tumors those who received chemotherapy had better OS compared with those who did not, P=0.019; 5-year OS rates were 92.7% and 79.6%, respectively. CONCLUSIONS: A surveillance only strategy for patients with stage I malignant ovarian germ cell tumors is associated with excellent survival outcomes for patients with grade 2 or 3 immature teratoma or mixed germ cell tumors.

Clinicopathologic features of endometrial cancer with mismatch repair deficiency.

The inclusion of DNA mismatch repair (MMR) evaluation as a standard of care for endometrial cancer management will result in a growing population of patients with MMR deficiency and negative germline Lynch syndrome testing (MMR-deficient). In this systematic review and study, the clinicopathologic features of endometrial cancer in patients with MMR-intact, MLH1 methylation positive, MMR-deficient or Lynch syndrome are evaluated. A systematic search of online databases between 1990 and 2018 identified studies of endometrial cancer patients with tumour testing (MMR protein immunohistochemistry or microsatellite instability) and germline assessment for Lynch syndrome. Extracted data included tumour testing, germline genetic testing, age, body mass index (BMI), family history, tumour stage, grade and histologic type. Associations between MMR-intact, MLH1 methylation positive, MMR-deficient and Lynch syndrome groups were analysed using descriptive statistics. The comprehensive search produced 4,400 publications, 29 met inclusion criteria. A total of 7,057 endometrial cancer cases were identified, 1,612 with abnormal immunohistochemistry, 977 with microsatellite instability. Nine-hundred patients underwent germline genetic testing, identifying 212 patients with Lynch syndrome. Patients in the Lynch syndrome and MMR-deficient groups were significantly younger than patients in the MMR-intact and MLH1 methylation positive groups. Patients with MMR-intact tumours had the highest BMI, followed by MMR-deficient, then Lynch syndrome. MMR-intact tumours were more likely to be grade I at diagnosis than other groups. Patients with Lynch syndrome and MMR-deficient tumours were less likely to have stage I disease as compared to patients with MMR-intact tumours. Endometrial cancer patients with MMR-deficient tumours have similar features to those with germline Lynch syndrome mutations, including age, grade, histology and stage. Even in the absence of a germline mutation, tumour evaluation for MMR status may have important clinical implications.

Is hysterectomy necessary for the treatment of preinvasive stratified mucin producing intraepithelial lesions of the cervix?

OBJECTIVES: Stratified mucin producing intraepithelial lesion (SMILE) is an uncommon premalignant cervical intraepithelial lesion, characterized by histopathologic features resembling those observed in high grade squamous intraepithelial lesions and adenocarcinoma in situ of the cervix. Its hybrid morphology poses a pathologic challenge with no specific management guidelines. The goal of this study was to review the natural history of SMILE and treatment based outcomes. METHODS: A retrospective pathology review of all cases of cervical intraepithelial lesions, with confirmation of all SMILE lesions, at one institution between 2007 and 2019, was performed. Clinical and pathologic characteristics, management options, and patient outcomes were reviewed and analyzed. Inclusion criteria included all patients diagnosed initially with SMILE on biopsy, excisional procedure, or simple hysterectomy. Patients diagnosed with SMILE had to fulfill the following pathologic features: stratified columnar epithelium with nuclear atypia and mucin production throughout the epithelial thickness with increased mitotic activity, and/or apoptotic bodies. Pathologic slides were re-evaluated by a pathologist to confirm the diagnosis and review margin status. RESULTS: 24 patients with SMILE were identified. Mean age at diagnosis was 36.2 years (range 25-53) with 67% (16/24) diagnosed before the age of 40. The majority (54%, 13/24) were nulliparous and 63% (15/24) had a past history of abnormal Pap smears. 92% (22/24) of patients were positive for high risk human papillomavirus, with 13% (n=3) presenting with a normal Pap smear. Diagnosis was made primarily on colposcopy (n=16), cold knife cone/loop electrosurgical excision procedure (n=7), or hysterectomy (n=1). Most patients (71%, 17/24) had a co-existing precancerous lesion at the time of diagnosis and the most common was high grade squamous intraepithelial lesion (53%). Five invasive lesions were also identified at the time of diagnosis of SMILE (2 adenocarcinoma, 3 adenosquamous), 1 of which underwent chemoradiation. Among all patients, 25% (6/24) underwent hysterectomy (4 simple, 2 radical), while 63% (17/24) of patients underwent a fertility sparing excisional procedure; 4% (1/24) were incidentally diagnosed on hysterectomy. 18 patients had negative margins and 2 patients had positive margins. Over a median follow-up of 29 months (range 3-105), all of the fertility sparing patients with negative margins had no recurrence. Among the two patients with positive margins, one had no recurrence on repeat excision and the other underwent repeat excision with persistent SMILE identified, subsequent negative margin, and no recurrence since. DISCUSSION: Our data showed that most patients with SMILE were young, positive for high risk human papillomavirus, nulliparous, and presented with coexisting lesions. Excisional procedures with negative margins may be sufficient fertility sparing treatment in patients with preinvasive SMILE with a low risk of recurrence. There should be consideration of hysterectomy at the completion of childbearing.

Outcomes of minimally invasive surgery for patients with endometrial carcinoma involving the cervix.

OBJECTIVE: Most studies evaluating the oncologic safety of minimally invasive surgery for endometrial cancer focus on patients with stage I disease. The aim of this study was to investigate the outcomes of minimally invasive surgery for patients with endometrial carcinoma involving the cervix. METHODS: Patients diagnosed between January 2010 and December 2015, with clinical stage II endometrial carcinoma, who underwent hysterectomy with lymphadenectomy, were drawn from the National Cancer Database. Inclusion criteria were clinical International Federation of Gynecology and Obstetrics (FIGO 2009) stage II, patients who underwent hysterectomy with lymphadenectomy, and known route of surgery (open or minimally invasive). Patients who received radiation therapy prior to surgery, those who had subtotal/supracervical hysterectomy, or unknown type of hysterectomy were excluded. The exposure of interest was performance of minimally invasive surgery either laparoscopic or robotic-assisted. Overall survival (primary endpoint) was assessed for patients diagnosed between January 2010 and December 2014 following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for confounders. RESULTS: A total of 2175 patients were identified and 1282 (58.9%) had minimally invasive surgery. Of these, 339 and 943 patients had laparoscopic or robotic-assisted laparoscopic hysterectomy, respectively. Minimally invasive surgery was converted to open surgery in 74 (5.8%) patients. Those undergoing minimally invasive surgery had shorter hospital stay (median 1 vs 3 days, p<0.001), lower unplanned readmission rate (2.7% vs 4.7%, p=0.014), and 90-day mortality (0.8% vs 1.8%, p=0.05). Patients who had open surgery (n=796) had worse overall survival compared with those who had minimally invasive surgery (n=1048, p=0.003); 3-year overall survival rates were 76.8% and 83.6%, respectively. After controlling for patient age, race, type of insurance, presence of co-morbidities, performance of extensive lymphadenectomy, presence of positive lymph nodes, tumor histology, presence of lymphovascular space invasion, tumor size, and administration of radiotherapy, performance of minimally invasive surgery was not associated with worse survival (HR 0.90, 95% CI 0.73 to 1.11). CONCLUSIONS: In this retrospective analysis, minimally invasive surgery in patients with stage II endometrial carcinoma was associated with superior short-term peri-operative outcomes and improved 3-year overall survival.

Primary total hip replacement in Ficat-Arlet stage 3 and 4 osteonecrosis: a retrospective study at a minimum 12-year follow-up.

INTRODUCTION: Results of total hip replacement (THR) for aseptic osteonecrosis are controversial and conflicting according to implant type and generation. The present study consisted in a retrospective assessment of implant survival in primary THR for aseptic osteonecrosis, using a cemented stem, standard polyethylene press-fit acetabular component, and metal-metal bearing. The study hypothesis was that THR results are equivalent between aseptic osteonecrosis and osteoarthritis of the hip. MATERIAL AND METHOD: A single-center retrospective study included 54 patients with metal-on-metal THR for femoral head osteonecrosis. The main endpoint was revision surgery for all causes, whether implant related or procedure related; secondary endpoints were complications and progression in clinical scores. RESULTS: Mean follow-up was 13.9 ± 1.6 years (range 12.0-17.1 years). Eighteen of the 54 patients (33.3%) died. Implant survival at last follow-up was 93.8% (95% CI, 87.1-100). There were 12 complications (22.2%): 1 intraoperative, 5 (9.3%) immediate postoperative, and 6 (11.1%) long term. Clinical assessment found a significant 43.1 point improvement in mean Harris score (p = 8.4E-33) and a 5.6 point improvement in mean PMA score (p = 2.9E-22). CONCLUSION: Survival in primary THR for aseptic osteonecrosis was good. Follow-up needs to be rigorous to screen for onset of complications. Primary THR is thus justified in Ficat-Arlet stage 3 and 4 aseptic osteonecrosis of the hip. LEVEL OF EVIDENCE: IV.

Low-grade serous ovarian cancer: State of the science.

In January 2019, a group of basic, translational, and clinical investigators and patient advocates assembled in Miami, Florida, to discuss the current state of the science of low-grade serous carcinoma of the ovary or peritoneum-a rare ovarian cancer subtype that may arise de novo or following a diagnosis of serous borderline tumor. The purpose of the conference was to review current knowledge, discuss ongoing research by established researchers, and frame critical questions or issues for future directions. Following presentations and discussions, the primary objective was to initiate future collaborations, uniform database platforms, laboratory studies, and clinical trials to better understand this disease and to advance clinical care outside the boundaries of single academic institutions. This review summarizes the state of the science in five principal categories: epidemiology and patient outcomes, pathology, translational research, patient care and clinical trials, and patients' perspective.

Primary malignant ovarian carcinoid; management and outcomes.

OBJECTIVE: To investigate the clinicopathological characteristics and survival of patients with malignant ovarian carcinoid tumor (OC). MATERIALS AND METHODS: The National Cancer Database was accessed and patients diagnosed between 2004 and 2015 with a OC who did not have a personal history of a tumor at another site were selected. Overall survival (OS) was assessed for patients who had ≥1 month of follow-up. OS rates were estimated following generation of Kaplan-Meier curves and compared with the log-rank test. RESULTS: A total of 588 patients with a median age of 51.5 years were identified. The majority were White (71.6%), had unilateral tumors (94.2%) with a median size of 3.8 cm that were confined to the ovary (88%). Patients with early stage disease (n = 431) had excellent OS compared to those with advanced stage (II-IV) disease (n = 51), p < 0.001; 5-yr OS rates were 95.4% and 53.1% respectively. For patients with stage I disease, there was no difference in OS between those who did (n = 211) and did not (n = 175) have hysterectomy, p = 0.92. For patients with advanced stage disease, administration of adjuvant chemotherapy was not associated with better survival, p = 0.093. CONCLUSIONS: OCs are typically small, unilateral tumors confined to the ovary arising in perimenopausal patients. Survival outcomes are excellent for patients with early stage disease and unilateral salpingo-oophorectomy appears to be curative.

Prospective Feasibility Trial of a Novel Strategy of Facilitated Cascade Genetic Testing Using Telephone Counseling.

PATIENTS AND METHODS: Probands with newly diagnosed cancer-associated pathogenic variants were offered facilitated cascade testing whereby the genetics team identified and contacted ARRs by telephone to disclose the familial pathogenic variant and offer telephone counseling and mailed saliva testing. Results and guideline-based recommendations were reviewed by telephone and shared with the primary care physician. RESULTS: Thirty probands were enrolled, and 114 ARRs were identified. Twelve ARRs were excluded (lived outside of the United States, n = 5; proband did not approve of contact, n = 7). Among 102 ARRs telephoned, contact was established with 95 (93%). Among 114 identified ARRs, 66 (58%) completed genetic testing. Among those completing testing, 27 (41%) carried the familial pathogenic variant. Surveys of ARRs at the time of genetic testing and 6 months later demonstrated low levels of anxiety, depression, distress, and uncertainty and high levels of satisfaction with testing. At 6 months, 7 ARRs with pathogenic variants had undergone cancer surveillance interventions and 4 had undergone cancer risk-reducing surgery. CONCLUSION: Facilitated cascade testing with telephone genetic counseling and mailed saliva kits resulted in high testing uptake among ARRs. Positive genetic testing resulted in utilization of genetically targeted primary disease prevention at short-term follow-up. Facilitated cascade testing is a straightforward, low-cost, easily implemented strategy with significant potential to promote early detection for affected ARRs and reduce cancer mortality and should be evaluated in larger scale clinical trials.

Disparities in the Use of Adjuvant External Beam Radiation Therapy in Node-positive Cervical Cancer Patients Following Hysterectomy.

OBJECTIVE: The objective of this study was to investigate the use of adjuvant external beam radiation therapy (EBRT) among patients with early-stage cervical carcinoma metastatic to regional lymph nodes (LNs). MATERIALS AND METHODS: The National Cancer Database was accessed and patients with early-stage cervical carcinoma diagnosed between 2004 and 2015 were identified. Those with regional LN metastases who had a hysterectomy were selected and administration of adjuvant EBRT was evaluated. Travel distance from the reporting facility was categorized into short (<12.5 miles), intermediate (12.5 to 49.9 miles) and long (>49.9 miles). RESULTS: A total of 3436 patients met the inclusion criteria; the rate of EBRT use was 69.7%. Black women were less likely to receive EBRT compared with white (64.2% vs. 70.6%, P=0.037), while patients who had radical hysterectomy were more likely to receive EBRT compared with those who had simple hysterectomy (72.6% vs. 66%, P<0.001). Rates of EBRT administration for patients who traveled short distance was 74.3% compared with 68.9% and 56.9% for those who traveled intermediate and long distance, respectively (P<0.001). On multivariate analysis, patients who traveled long (odds ratio: 0.44, 95% confidence interval [CI]: 0.36, 0.54) or intermediate (OR: 0.73, 95% CI: 0.61, 0.86) distances were less likely to receive EBRT. After controlling for age, race, insurance, presence of comorbidities, stage, histology, and type of hysterectomy, omission of EBRT was associated with worse survival (hazard ratio: 1.53, 95% CI: 1.32, 1.78). CONCLUSIONS: A large percentage of patients with early-stage cervical cancer and positive LNs did not receive EBRT following hysterectomy. Black women were less likely to receive EBRT than white women. Travel burden may negatively influence appropriate treatment.

Evaluation of lysophosphatidic acid in vaginal fluid as a biomarker for ovarian cancer: A pilot study.

There remains a need to differentiate between women with a benign or a malignant adnexal mass prior to surgery. As part of an ongoing evaluation of vaginal fluid compounds as potential tumor biomarkers we evaluated whether vaginal lysophosphatidic acid (LPA) predicted the subsequent diagnosis of a malignant adnexal mass. In this prospective pilot study vaginal fluid was obtained from 100 post-menopausal women referred for evaluation of a suspicious adnexal mass and tested for LPA by ELISA. Clinical data and serum CA125 results were obtained only after completion of all laboratory testing. Twenty eight of the women were subsequently diagnosed with an ovarian malignancy, four had a borderline tumor and 68 had a benign diagnosis. Among women with a malignant ovarian mass, 11 (39.3%) had an endometrioid adenocarcinoma +/- Clear cell tumor components, 6 (21.4%) had a high grade serous carcinoma, 3 (10.7%) had a mucinous tumor, 2 each (7.1%) had a malignant mixed mesodermal or a granulosa tumor and 1 each (3.6%) had a Clear cell tumor, a mixed cell tumor, leimyosarcoma or metastatic adrenal tumor. Compared to the median vaginal LPA level in women with benign lesions (1.5 µM), LPA was significantly elevated only in women with endometrioid ovarian cancer (7.9 µM) (p = 0.0137). Of the 6 endometrioid tumors in which values for both plasma CA125 and vaginal LPA were available 5 were positive only for LPA while one was only CA125 positive. Detection of LPA in vaginal secretions may be of value for the noninvasive diagnosis of endometrioid ovarian malignancies in post-menopausal women.

Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population?

BACKGROUND: Universal tumor testing for defective DNA mismatch repair (MMR) is recommended for all women diagnosed with endometrial cancer to identify those with underlying Lynch syndrome. However, the effectiveness of these screening methods in identifying individuals with Lynch syndrome across the population has not been well studied. The aim of this study was to evaluate outcomes of MMR immunohistochemistry (IHC), mutL homolog 1 (MLH1) methylation, and microsatellite instability (MSI) analysis among patients with endometrial cancer. METHODS: A complete systematic search of online databases (PubMed, EMBASE, MEDLINE, and the Cochrane Library) for 1990-2018 was performed. A DerSimonian-Laird random effects model meta-analysis was used to estimate the weighted prevalence of Lynch syndrome diagnoses. RESULTS: The comprehensive search produced 4400 publications. Twenty-nine peer-reviewed studies met the inclusion criteria. Patients with endometrial cancer (n = 6649) were identified, and 206 (3%) were confirmed to have Lynch syndrome through germline genetic testing after positive universal tumor molecular screening. Among 5917 patients who underwent tumor IHC, 28% had abnormal staining. Among 3140 patients who underwent MSI analysis, 31% had MSI. Among patients with endometrial cancer, the weighted prevalence of Lynch syndrome germline mutations was 15% (95% confidence interval [CI], 11%-18%) with deficient IHC staining and 19% (95% CI, 13%-26%) with a positive MSI analysis. Among 1159 patients who exhibited a loss of MLH1 staining, 143 (13.7%) were found to be MLH1 methylation-negative among those who underwent methylation testing, and 32 demonstrated a germline MLH1 mutation (2.8% of all absent MLH1 staining cases and 22.4% of all MLH1 methylation-negative cases). Forty-three percent of patients with endometrial cancer who were diagnosed with Lynch syndrome via tumor typing would have been missed by family history-based screening alone. CONCLUSIONS: Despite the widespread implementation of universal tumor testing in endometrial cancer, data regarding testing results remain limited. This study provides predictive values that will help practitioners to evaluate abnormal results in the context of Lynch syndrome and aid them in patient counseling.

Impact of hospital surgical volume on complete gross resection (CGR) rates following primary debulking surgery for advanced stage epithelial ovarian carcinoma.

BACKGROUND: To investigate the impact of hospital surgical volume on the rate of complete gross resection for patients with advanced stage epithelial ovarian carcinoma undergoing primary debulking surgery. METHODS: The National Cancer Data Base was used to identify patients undergoing between 2010 and 2014 for an advanced stage (III-IV) epithelial ovarian cancer. For analyses purposes facility surgical volume was divided into tertiles (high, intermediate and low). Patients with bulky stage III disease who underwent primary debulking surgery with known residual disease status were selected for further analysis. RESULTS: A total of 8894 patients with macroscopic peritoneal disease were included. Rates of complete gross resection for patients managed in low, intermediate and high-volume centers were 41.0%, 41.6% and 43.3% respectively (p = 0.20). After controlling for year of diagnosis, age, insurance status, presence of co-morbidities, histology, size of peritoneal implants, stage, and complexity of surgery, patients undergoing primary debulking surgery at low (OR: 0.85, 95% CI: 0.74, 0.97, p = 0.013) and intermediate (OR: 0.90, 95% CI: 0.82, 0.99, p = 0.043) volume centers had a lower likelihood of achieving complete gross resection compared to those managed in high volume centers. CONCLUSIONS: After controlling for multiple potential confounders, patients receiving surgery in high volume centers had a higher likelihood of complete gross resection following primary debulking surgery for advanced-stage epithelial ovarian cancer.

Role of adjuvant chemotherapy in the management of non-granulosa cell ovarian sex cord-stromal tumors.

OBJECTIVE: To investigate the role of adjuvant chemotherapy (CT) in the management of ovarian non-granulosa cell (GC) sex cord-stromal tumors (SCSTs). METHODS: The National Cancer Database was accessed and patients diagnosed between 2004 and 2013 with a malignant non-GC SCST were selected. Overall survival (OS) was evaluated with Kaplan-Meier curves and compared with the log-rank test. Multivariate survival analysis was performed with Cox regression. Factors associated with the administration of CT were evaluated with the chi-square test and binary logistic regression. RESULTS: A total of 391 patients were identified. The majority had a Sertoli-Leydig cell tumor (SLCT) (73.2%) and early stage disease (84.8%). A total of 203 (51.9%) patients received CT. Advanced disease stage, younger age, high-grade histology, White race, large tumor size and SLCT histology were associated with administration of CT. For patients with early stage disease, there was no difference in OS between those who did (n=134) and did not receive CT (n=157), p=0.40; 5-year OS rates were 81.7% and 84.6%, respectively. No mortality benefit was observed (hazard ratio=0.73; 95% confidence interval=0.38-1.4) after controlling for tumor histology. Median OS of women with advanced stage disease who received CT (n=41) was 34.96 months compared to 15.51 months for those who did not (n=11), p=0.013. CONCLUSION: Adjuvant CT was associated with improved survival for patients with advanced stage non-GC SCSTs. No clear benefit was found for those with early stage disease.

Prognostic significance of residual disease in advanced stage malignant ovarian germ cell tumors.

OBJECTIVE: To investigate the prognostic significance of complete gross resection following cytoreductive surgery for patients with advanced stage malignant ovarian germ cell tumors. METHODS: The National Cancer Data Base was accessed and patients diagnosed with an advanced stage (II-IV) malignant ovarian germ cell tumor who underwent primary cytoreductive surgery between 2011 and 2014 were selected for further analysis. For analysis purposes two groups were formed: patients with complete gross resection and those with macroscopic residual disease. Demographic and clinico-pathological characteristics were compared with the chi-square and Mann-Whitney U test. Univariate survival analysis was performed with the log-rank test after generation of Kaplan-Meier curves, while a Cox proportional hazard model was constructed to evaluate mortality after controlling for confounders. RESULTS: A total of 343 patients who met the inclusion criteria were identified. Residual disease status was available for 276 patients: the rate of complete gross resection was 69.2 %. By univariate analysis there was no difference in overall survival between patients in the complete gross resection and macroscopic residual disease groups, P= 0.26; 3-year overall survival rates: 86.4 % and 82.8 %, respectively. No difference in overall survival was noted following stratification by histology; P = 0.64 and P = 0.24 for dysgerminoma and non-dysgerminoma tumor groups. After controlling for stage IV disease, histology and the administration of chemotherapy, macroscopic residual disease was not associated with a worse mortality (HR: 1.22, 95% CI: 0.61 to 2.46). CONCLUSIONS: Macroscopic residual disease following primary cancer-directed surgery was not associated with a worse prognosis in a cohort of patients with advanced stage malignant ovarian germ cell tumors.

Prevalence of nonfounder BRCA1/2 mutations in Ashkenazi Jewish patients presenting for genetic testing at a hereditary breast and ovarian cancer center.

BACKGROUND: Genetic assessment in Ashkenazi Jewish (AJ) patients often is limited to BRCA1/2 founder mutation testing. With access to time-efficient and cost-efficient multigene panel testing, some advocate expanding genetic testing in this population. However, to the best of the authors' knowledge, rates of nonfounder BRCA1/2 mutations and mutations in cancer-associated genes other than BRCA1/2 among AJ are not known. In the current study, the authors sought to assess the prevalence of mutations other than BRCA1/2 founder mutations among AJ patients undergoing genetic assessment. METHODS: The authors reviewed the medical records for all AJ patients who underwent genetic assessment at a single institution between June 2013 and December 2016. Mutations were categorized as 1) BRCA1/2 AJ founder mutations (BRCA1 185delAG, BRCA1 5382insC, or BRCA2 6174delT); 2) nonfounder BRCA1/2 mutations; or 3) mutations in non-BRCA1/2 cancer-associated genes. RESULTS: A total of 732 AJ patients underwent genetic assessment. Of these, 371 patients (51%) had a personal history of breast or ovarian cancer, 540 patients (73.8%) had a family history of breast cancer, and 132 patients (18%) had a family history of ovarian cancer. In the study population, 101 patients (13.8%) were found to have a pathogenic mutation, 78 patients (10.7%) had a BRCA1/2 founder mutation, 3 patients (0.4%) had a nonfounder BRCA1/2 mutation, and 20 patients (2.7%) had a mutation in a non-BRCA1/2 cancer-associated gene. Non-BRCA1/2 cancer-associated genes harboring mutations included RAD51D, TP53, mutS homolog 6 (MSH6), checkpoint kinase 2 (CHEK2), adenomatous polyposis coli (APC), and Fanconi anemia group C protein (FANCC). CONCLUSIONS: Among AJ patients found to have a pathogenic mutation on genetic assessment, approximately 22.8% had a mutation that would be missed with BRCA1/2 AJ founder mutation testing. Comprehensive multigene panel sequencing can provide clinically relevant genetic information for AJ patients and should be considered for genetic assessment in this population.

Minimally Invasive Staging of Apparent Stage I Malignant Ovarian Germ Cell Tumors: Prevalence and Outcomes.

STUDY OBJECTIVE: Evaluate the prevalence, trends, and outcomes of minimally invasive surgical (MIS) staging of malignant ovarian germ cell tumors (MOGCTs) apparently confined to the ovary. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Participating hospitals in the National Cancer Data Base. PATIENTS: Women diagnosed between 2010 and 2014 with a MOGCT apparently confined to the ovary with information on the planned surgical approach. INTERVENTIONS: Staging with MIS or laparotomy. MEASUREMENT AND MAIN RESULTS: A total of 918 patients were identified. MIS was planned for 294 patients (32%): a laparoscopic approach for 237 patients and a robotic-assisted approach for 57 patients. Rate of conversion to laparotomy was 11% (46 cases), 1.7% and 15.6% in the robotic and laparoscopy groups, respectively (p = .003). No difference in the use of MIS was noted based on year of diagnosis (p = .38). By multivariate analysis white race, higher level of education, and smaller tumor size were associated with the receipt of MIS. Patients in the MIS group were less likely to undergo lymph node dissection (39.6% vs 51.3%, p = .001) and omentectomy (18.7% vs 28.5%, p = .002). Hospital stay after surgery was shorter for patients who had MIS (median, 2 vs 3 days; p <.001). Unplanned 30-day readmission rate was also lower in the MIS group (1.4% vs 3.9%, p = .043). No difference in overall survival was noted between the 2 groups (p = .81). CONCLUSION: MIS for apparent early-stage MOGCTs was less comprehensive but associated with a decreased hospital stay and unplanned readmission rate.

Small Cell Carcinoma of the Ovary: A Rare Tumor With a Poor Prognosis.

OBJECTIVE: The aim of this study was to investigate the demographic and clinicopathological characteristics and prognosis of women diagnosed with small cell carcinoma of the ovary. METHODS: The National Cancer Data Base was accessed, and women diagnosed with small cell carcinoma of the ovary, between 2004 and 2014 were identified. Median and 3- and 5-year overall survival (OS) rates were calculated following generation of Kaplan-Meir curves and compared with the log-rank test. A Cox multivariate model was constructed to identify variables associated with mortality. RESULTS: A total 469 women were identified with a median age of 39 years; 81.7% of tumors were unilateral, whereas median size was 13 cm. Only 20.1% of patients had stage I disease. Women who underwent cancer-directed surgery had a 5-year OS rate of 24.1%. Five-year OS rates were 48.6%, 30.7%, 18%, and 12.3% for those with stages I, II, III, and IV disease, respectively, P < 0.001. Younger age (P = 0.013) and the combination of surgery with chemotherapy (CT) (P < 0.001) were associated with superior OS. By multivariate analysis, earlier disease stage and use of CT, but not patient age or performance of lymphadenectomy, were associated with lower mortality. CONCLUSIONS: Small cell carcinomas of the ovary are unilateral tumors primarily arising in premenopausal women. Multimodal treatment with cancer-directed surgery and CT results in a modest increase of a generally poor survival.