83 research outputs found
19 Overall survival after surgical staging by lymph node dissection versus sentinel lymph node biopsy in endometrial cancer: a national cancer database study
No full textObjectives To investigate the association between the type of lymph node (LN) assessment and overall survival (OS) in endometrial cancer (EC). Methods Patients with stage I-III EC who underwent a hyster- ectomy and LN assessment from 2012 to 2015 were identi- fied from the National Cancer Database. Multivariable Cox proportional hazards regression analysis was performed to assess factors associated with OS. Results Of 68,614 patients identified, 64,796 underwent lym- phadenectomy (LND) only, 1,777 sentinel lymph node biopsy only (SLN-B), and 2,041 both procedures (SLN-B/LND). On multivariable analysis, SLN-B and SLN-B/LND were not associ- ated with different OS compared to LND (hazard ratio [HR]: 0.92; 95%CI: 0.73–1.17 - HR: 0.91; 95%CI: 0.77–1.07,respectively). Similarly, when stratified by LN status, SLN-B and SLN-B/LND reported similar OS compared to LND, both in negative (HR: 1.03; 95%CI: 0.85–1.26 – HR :0.95; 95% CI: 0.73–1.23, respectively) and positive (HR: 0.92; 95%CI: 0.55–1.54 – HR: 0.76; 95%CI: 0.57–1.03, respectively) LNs. Including only LND with !10 pelvic and !1 para-aortic LNs removed, no difference in OS was observed between LND and SLN-B or SLN-B/LND in the entire cohort, and in nega- tive or positive LNs. In all analyses, older age, Charlson-Deyo Score !2, black race, higher American Joint Committee on Cancer (AJCC) pathologic T stage, grade 3, presence of lym- phovascular infiltration, type-2 histology, and absence of che- motherapy or radiation therapy were independently associated with worse OS. Conclusions When compared to SLN-B or SLN-B/LND, LND does not appear to improve OS in EC, even in the presence of LN metastases
Adoption of Minimally Invasive Surgery and Decrease in Surgical Morbidity for Endometrial Cancer Treatment in the United States
No full textTo assess how the widespread adoption of minimally invasive surgery in the United States is associated with changes in 30-day morbidity and mortality in endometrial cancer treatment.OBJECTIVE: To assess how the widespread adoption of minimally invasive surgery in the United States is associated with changes in 30-day morbidity and mortality in endometrial cancer treatment. METHODS: In this retrospective cohort study, the American College of Surgeons' National Surgical Quality Improvement Project database for 2008-2014 was reviewed for patients who had undergone surgery for endometrial cancer according to their primary Current Procedural Terminology (CPT) codes. Women with CPT codes for advanced cancer or with disseminated disease were excluded. A trend analysis across the time period by surgical approach (open surgery through laparotomy, vaginal surgery, and minimally invasive surgery) was performed using a Cochran-Armitage test for trend. Thirty-day surgical outcomes were compared between patients who had minimally invasive surgery and open surgery. Inverse probability of treatment weighting models were used to investigate the independent effect of minimally invasive surgery on 30-day outcomes.RESULTS: Overall, 12,283 patients met the inclusion criteria. A significant implementation of minimally invasive surgery (24.2-71.4%) and a concomitant decrease in open surgery through laparotomy (71.1-26.4%) were observed from 2008 to 2014 (both P<.001). Rate of vaginal surgery did not change over time (1.5-2.2%, P=.06). After adjusting for possible confounders, open surgery (compared with minimally invasive surgery) was independently associated with increased odds of major complications (n=347 versus n=274, adjusted odds ratio [OR] 2.4, 95% CI 2.0-2.8), readmission (n=269 versus n=238, adjusted OR 2.2, 95% CI 1.8-2.6), reoperation (n=80 versus n593, adjusted OR 1.5, 95% CI 1.2-2.1), superficial surgical site infection (n=190 versus n=55, adjusted OR 6.8, 95% CI 5.0-9.2), perioperative transfusion (n=430 versus n=149, adjusted OR 5.9, 95% CI 4.8-7.1), and death (n=41 vs, n=20, adjusted OR 3.8, 95% CI 2.2-6.6). A comprehensive decrease in 30-day morbidity for the treatment of endometrial cancer overall was observed from 2008 to 2014 (P<.001), whereas 30-daymortality remained stable (P=.24).CONCLUSION: The widespread adoption of minimally invasive surgery is associated with substantial decreases in 30-day morbidity, readmission, and reoperation for women treated for endometrial cancer in the United States
Abstract P1-11-08: Tumor and procedural factors associated with positive margins at lumpectomy in women undergoing breast conservation surgery
No full textAbstract
Background:
Negative margins are important in decreasing risk of local recurrence after breast conservation surgery. Further, positive margins on final pathology require a second operation, burdening patients and increasing costs. We identified factors predicting positive margins at lumpectomy prompting intraoperative re-excision in a large referral center.
Methods
With IRB approval we reviewed all breast cancer lumpectomy cases from January 2012 to December 2013. Associations between rates of positive margin (defined as tumor at ink) and patient and tumor factors were assessed using chi square tests and univariate and adjusted multivariable logistic regression, overall and stratified by DCIS or invasive cancer.
Results
385 patients (105 DCIS and 280 invasive disease) were identified. Overall positive margin rate at lumpectomy requiring intraoperative re-excision was 62.3% and was higher in DCIS than in invasive disease (78.1% vs 56.4%, OR=2.78, p=0.001). Positive margin rates did not vary by surgeon, patient age, ER, PR or HER2 status of the tumor. On univariate analysis higher tumor grade was associated with a higher margin positive rate (grade 3 vs grade 1, OR=1.71, p=0.049).
Within the 105 DCIS cases, no factors had statistically significantly different odds of positive margins on univariate or multivariable analysis.
Within the 280 cases of invasive breast cancer, factors independently associated with lower odds of margin positivity were neoadjuvant chemotherapy (OR 0.30, p=0.037, relative to no neoadjuvant therapy) and seed localized excision (OR 0.24, p=0.03, relative to no localization).
Multivariable Logistic Regression* Modeling DCISInvasive DiseaseVariableOdds RatioP-valueOdds RatioP-valueAge 50+ vs Age &lt;502.860.111.590.23Grade 2 vs Grade 10.940.921.500.21Grade 3 vs Grade 13.250.121.580.37Estrogen Receptor Positive vs Negative3.950.221.640.42Progesterone Receptor Positive vs Negative0.840.871.110.84Her2 Positive vs Negative 1.270.68Stage T2 vs T1 2.540.45Stage T3 vs T1 2.180.69Ki67 &lt;15% vs 15%+ 0.570.09Neoadjuvant Chemotherapy vs None 0.300.04Seed Localization vs No Localization 0.240.03Wire Localization vs No Localization 0.330.13Intraoperative Ultrasound vs No Localization 0.670.53*adjusted for individual surgeons (all p &gt;0.05)
Conclusion
DCIS was associated with higher rate of positive margins at lumpectomy than invasive breast cancer. Within invasive disease, neoadjuvant chemotherapy and seed localization were associated with lower rates of margin positivity. Strategies to decrease positive margins would be best employed in cases of lumpectomy for DCIS and for invasive disease treated without neoadjuvant chemotherapy. Seed localization may be one strategy to lower positive margin rates.
Citation Format: Boughey JC, Keeney MG, Glasgow AE, Keeney GL, Habermann EB. Tumor and procedural factors associated with positive margins at lumpectomy in women undergoing breast conservation surgery [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-11-08.</jats:p
Abstract PD7-05: How 21-gene recurrence score assay is being used to individualize adjuvant chemotherapy recommendations in ER+/HER2 -node positive breast cancer -A national cancer data base study
No full textAbstract
Introduction: The 21-gene Recurrence Score (RS) assay has been shown in retrospective studies to predict benefit of adjuvant chemotherapy (AC) in node positive (N+) breast cancer (BC) patients (pts). This study evaluates the trends and patterns of use of RS assay in N+, ER+/HER2-breast cancer and the impact of RS on decision to use AC in a real-world multi-institutional database.
Methods: Pts with T1-T4c, N1mi-N3, ER+/HER2- BC diagnosed between 2010 and 2013, included in the National Cancer Data Base were analyzed. Pts who received neo-AC were excluded. Analyses included Cochrane-Armitage tests for trends and multivariable logistic regression assessing factors influencing RS testing and AC recommendations based on RS.
Results: Among 73,049 pts, RS was obtained in 20.6%, increasing from 14.9% in 2010 to 24.4% in 2013 (p&lt;0.001). RS testing was most common in N1mi (43.6%) and N1 (22.0%) and rare in N2/N3 (3.3%) BC. Of the 12,540 BC with quantitative RS results, 61.1% were low RS, 32.3% intermediate RS and 6.6% high RS. AC recommendation was less frequent in pts with RS testing compared to pts not tested (50.4% recommended AC vs 80.9%, p&lt;0.001). In pts with N1mi/N1 BC, recommendation rates for AC were higher with higher RS (see table), however in N2/N3 BC, AC was recommended in the majority (71-88%) regardless of RS. Most pts (&gt;85%) with RS 26-30 or high risk RS were recommended AC regardless of N stage. For pts with low risk RS, recommendation for AC increased significantly with increasing N stage (see table). On multivariable analysis, in pts with low risk RS, AC was more likely to be recommended in those with N1/N2+ stage (OR 2.3 and 9.1 vs N1mi), T2 and T3/T4 tumors (OR 1.3 and 2.2 vs T1 tumors), poorly differentiated tumors (OR 1.6) and younger age (OR 3.4 and 1.7, respectively, for &lt;40 and 40-49 vs 50-59) (all p&lt;0.001). Among pts with RS 18-25, AC was more likely to be recommended in those with higher tumor grade, younger age but the effect of N stage was less pronounced. Histology (IDC vs ILC) did not influence AC recommendation in any RS subset.
Path N StageRS Risk GroupLow RiskIntermediate RiskHigh RiskRS&lt;18RS 18-25RS 26-30RS&gt;30N1mi AC No1,854 (75.9%)389 (36.9%)36 (14.6%)16 (7.0%)N1mi AC Yes590 (24.1%)666 (63.1%)210 (85.4%)212 (93.0%)N1 AC No3,000 (60.6%)699 (33.0%)75 (14.8%)33 (6.0%)N1 AC Yes1,954 (39.4%)1,422 (67.0%)431 (85.2%)518 (94.0%)N2/N3 AC No76 (29.0%)17 (16.7%)3 (12.5%)7 (14.9%)N2/N3 AC Yes186 (71.0%)85 (83.3%)21 (87.5%)40 (85.1%)p-value&lt;0.001&lt;0.0010.880.16
Conclusions: RS was obtained in about one fifth of pts with N+ ER+/HER2- BC, predominantly for N1mi and N1 disease. Overall, RS testing decreased frequency of recommendation of AC in N+ BC pts. The RS influenced use of AC particularly in N1mi and N1 pts, likely avoiding overtreatment of those with low risk RS and RS 18-25. Prospective data regarding RS to direct AC in N+ BC are awaited.
Citation Format: Peethambaram PP, Hoskin TL, Heins CN, Habermann EB, Boughey JC. How 21-gene recurrence score assay is being used to individualize adjuvant chemotherapy recommendations in ER+/HER2 -node positive breast cancer -A national cancer data base study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD7-05.</jats:p
Abstract P3-01-01: Management of the axilla in metaplastic breast carcinoma
No full textAbstract
Background
Metaplastic breast cancer (MBC), characterized by a mixture of epithelial, squamous or mesenchymal elements and a usually triple-negative (TN) phenotype, accounts for &lt;1% of breast cancer diagnoses. MBC has a poor prognosis with frequent distant spread, but, paradoxically, a lower than expected rate of nodal positivity (6 to 40%). Due to its rarity there is little data on how best to evaluate and manage the axilla in women with these tumors. Thus we undertook this study to evaluate axillary management and oncologic outcomes.
Methods
With IRB approval, we identified adult patients diagnosed with MBC at our institution from 2001 to 2011 from our prospective surgical pathology database. Patient, pathology, imaging, treatment and outcome data were obtained from electronic medical record, tumor registry, pathology slide and imaging review. Median follow-up for surviving patients was 66 months. Statistical analyses were performed using JMP 10.0 software.
Results
We identified 41 MBC patients, median age 60 years (range 33-89 years), with a median tumor size of 2.7 cm; 33 (80%) were TN. 23 patients (56%) had a preoperative axillary ultrasound (AUS): 9 (39%) showed at least one suspicious axillary lymph node (LN) of whom 6 had a preoperative fine needle LN biopsy (FNA) of which 3 were positive for metastasis. 6 patients, including the 3 LN+ on FNA, had neoadjuvant chemotherapy (NAC). Operation included axillary dissection (ALND) in 14, sentinel LN biopsy (SLNB) in 23, and SLNB followed by ALND in 1, while 3 patients had no axillary surgery. 10 patients were LN+ at operation. Among 22 patients who had both an AUS and axillary surgery, AUS had a sensitivity of 100% and specificity of 78%. Patient and tumor variables in association with pathologic LN status are summarized in the table. LN positivity correlated with increasing tumor size, T stage, grade and angiolymphatic invasion. 16 patients recurred, most with distant disease (10/16, 63%), although there was a solitary axillary recurrence 8 months after a negative SLNB in one patient who did not have a preoperative AUS. Thus the accuracy of SLNB was 96% (23/24) overall, but among those without preoperative AUS, 1/7 (14%) SLNBs were falsely negative. 5-year disease-free and breast cancer-specific survival estimates were 49% and 63%.
LN- N=28 (74%)LN+ N=10 (26%)p-valueSize, median (IQR), cm2.7 (1.6-4.6)6.6 (2.5-16.5)0.001T stage 0.03T19 (100%)0 (0%) T214 (78%)4 (22%) T33 (60%)2 (40%) T42 (33%)4 (67%) Grade 0.04Low6 (16%)0 (0%) Intermediate/High22 (58%)10 (26%) Estrogen Receptor 0.61Positive (&gt;1%)5 (71%)2 (29%) Negative (&lt;1%)23 (74%)8 (26%) Angiolymphatic Invasion 0.002No26 (87%)4 (13%) Yes2 (25%)6 (75%) Dominant Histology 0.65Adenosquamous2 (100%)0 (0%) Matrix producing4 (80%)1 (20%) Spindle cell14 (74%)5 (26%) Squamous*8 (67%)4 (33%) *any squamous component
Conclusion
Our study is the first to specifically address AUS and SLNB for patients with metaplastic breast cancer. AUS had 100% sensitivity and 78% specificity, while one patient without a preoperative AUS had a falsely negative SLNB. Further, AUS with FNA of suspicious LNs was useful for staging at the time of diagnosis and informing treatment. We recommend this approach for patients with MBC.
Citation Format: Murphy BL, Fazzio RT, Hoskin TL, Glazebrook KN, Keeney MG, Habermann EB, Hieken TJ. Management of the axilla in metaplastic breast carcinoma [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-01.</jats:p
Regarding pathogenesis of middle ear cholesteatoma
No full textУ роботі автор дійшов висновку, що розвиток холестеатоми середнього вуха при хронічному
гнійному середньому отиті є результатом порушення нормальних процесів загоєння в кістковій рані.
Дотримуючись концепції Habermann, він вважає, що розвиток холестеатоми в середньому вусі
пов’язане з атипичним запальним розростанням вростаючого в середнє вухо епидермиса зовнішнього
слухового проходуThe author concludes in his work that cholesteatoma development in the middle ear at chronic otopyosis
media results from bony-wound reparation disorders. Following Habermann’s conception, the author suggests
that cholesteatoma development in the middle ear is linked to atypical inflammatory in-growth of the external
auditory canal epidermis into the middle ear cavity
Regarding pathogenesis of middle ear cholesteatoma
No full textУ роботі автор дійшов висновку, що розвиток холестеатоми середнього вуха при хронічному
гнійному середньому отиті є результатом порушення нормальних процесів загоєння в кістковій рані.
Дотримуючись концепції Habermann, він вважає, що розвиток холестеатоми в середньому вусі
пов’язане з атипичним запальним розростанням вростаючого в середнє вухо епидермиса зовнішнього
слухового проходуThe author concludes in his work that cholesteatoma development in the middle ear at chronic otopyosis
media results from bony-wound reparation disorders. Following Habermann’s conception, the author suggests
that cholesteatoma development in the middle ear is linked to atypical inflammatory in-growth of the external
auditory canal epidermis into the middle ear cavity
Author response
No full textHolliday junctions (HJs) are key DNA intermediates in homologous recombination. They link homologous DNA strands and have to be faithfully removed for proper DNA segregation and genome integrity. Here, we present the crystal structure of human HJ resolvase GEN1 complexed with DNA at 3.0 Å resolution. The GEN1 core is similar to other Rad2/XPG nucleases. However, unlike other members of the superfamily, GEN1 contains a chromodomain as an additional DNA interaction site. Chromodomains are known for their chromatin-targeting function in chromatin remodelers and histone(de)acetylases but they have not previously been found in nucleases. The GEN1 chromodomain directly contacts DNA and its truncation severely hampers GEN1's catalytic activity. Structure-guided mutations in vitroand in vivo in yeast validated our mechanistic findings. Our study provides the missing structure in the Rad2/XPG family and insights how a well-conserved nuclease core acquires versatility in recognizing diverse substrates for DNA repair and maintenance
Optimality considerations for propulsive fuselage power savings
No full textThe paper discusses optimality constellations for the design of boundary layer ingesting propulsive fuselage concept aircraft under special consideration of different fuselage fan power train options. Therefore, a rigorous methodical approach for the evaluation of the power saving potentials of propulsive fuselage concept aircraft configurations is provided. Analytical formulation for the power-saving coefficient metric is introduced, and, the classic Breguet–Coffin range equation is extended for the analytical assessment of boundary layer ingesting aircraft fuel burn. The analytical formulation is applied to the identification of optimum propulsive fuselage concept power savings together with computational fluid dynamics numerical results of refined and optimised 2D aero-shapings of the bare propulsive fuselage concept configuration, i.e. fuselage body including the aft–fuselage boundary layer ingesting propulsive device, obtained during the European Union-funded DisPURSAL and CENTRELINE projects. A common heuristic for the boundary layer ingesting efficiency factor is derived from the best aero-shaping cases of both projects. Based thereon, propulsive fuselage concept aircraft design optimality is parametrically analysed against variations in fuselage fan power train efficiency, systems weight impact and fuselage-to-overall aircraft drag ratio in cruise. Optimum power split ratios between the fuselage fan and the underwing main fans are identified. The paper introduces and discusses all assumptions necessary in order to apply the presented evaluation approach. This includes an in-depth explanation of the adopted system efficiency definitions and drag/thrust bookkeeping standards.Flight Performance and Propulsio
INFORMATE Project - CHORUS Report Summaries - 20231106
No full text<p>These data provide a summary of the All, Author Affiliation, and Dataset Reports generated by the <a href="https://dashboard.chorusaccess.org/">CHORUS Dashboard</a> for three agencies: the U.S. National Science Foundation, U.S. Geological Survey, and the U.S. Agency for International Development. The reports summarized here was collected on November 6-7, 2023 as part of the INFORMATE Project funded by NSF.</p><p>The columns are:</p><p>Column Definition</p><p>agency The funding agency [NSF, USGS, or USAID]</p><p>date. The date of data retrieval (YYYYMMDD)</p><p>report. The report [all, authors, datasets]</p><p>Property Name of the column in the input file</p><p>count Number of values (rows) of the property</p><p>unique Number of unique values of the property</p><p>top Most common value of the property</p><p>freq Number of occurrences (frequency) of the most common value</p><p>Count % The percentage of rows that include the property</p>
- …
