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Objectives: Endometrial cancer due to loss of mismatch repair proteins may be caused by epigenetic or genetic factors. Complete profiling is not routinely performed in clinical practice. We sought to explore outcomes of women with mismatch repair deficiency (MMRd) due to epigenetic MLH-1 promoter hypermethylation (MMRd-MLH). We hypothesize that MMRd-MLH correlates with worse clinical outcomes in endometrial cancer. Methods: Under an IRB protocol, we retrospectively identified patients with endometrioid endometrial adenocarcinoma undergoing hysterectomy at our institution from 2016-2020. These patients underwent routine immunohistochemical testing for MMRd, with subsequent genetic testing or methylation studies for loss of MMR proteins. We examined patient data in three cohorts: MMR proficient (MMRp), MMRd-MLH, and MMRd deficiency due to germline mutation (MMRd-G). We excluded patients who did not undergo MMR testing and those who were MMR deficient due to other causes. We examined clinical data via univariate and multivariate tests and Kaplan-Meier survival analyses. Results: We identified 327 patients who met the criteria for review. The majority (243, 74%) were MMRp, 74 (23%) were MMRd-MLH, and ten (3%) were MMRd-G. On univariate analysis, we observed no differences in the history of post-menopausal hormone replacement therapy, family history of cancer, personal history of hypertension or diabetes mellitus, or body mass index. We found that when compared to the other two groups, MMRd-MLH patients were more like to have grade 2-3 tumors (p < 0.01) and LVSI (p < 0.001). We identified statistically significant associations between age at surgery (60, 67, and 60 years, respectively) and depth of invasion (0.41cm, 0.67cm, and 0.18cm). We did not observe significant differences in the stage. We identified that MMRd-MLH was associated with pathologic high-intermediate risk factors leading to increased adjuvant therapy in stage I disease (p=0.04). We observed a 4.1% recurrence rate in MMRp compared to 8.1% in the MMRd-MLH group compared to no recurrences in MMRd-G (p = NS). When comparing MMRp and MMRd-MLH in Kaplan-Meier analyses, we observed a statistical difference in disease-free survival favoring those who were MMRp (p = 0.02). Median survival was not reached. There were no significant differences in overall survival between MMRp and MMRd-MLH. We did not identify independent prognostic factors for recurrence when controlling for age, stage, grade, or MMR status. [Display omitted] Conclusions: MMRd-MLH is associated with LVSI, higher grade, deeper tumor invasion, and a significantly higher rate of adjuvant therapy. We observed patients with MMRd-MLH were more likely to recur despite adjuvant therapy. MMRd-MLH may represent a poor prognostic factor and a target for further adjuvant therapy. [ABSTRACT FROM AUTHOR]

We hypothesize that women with brain metastases from endometrial cancer (EC) will share similar features of histology, initial stage, and time to recurrence. A retrospective chart review was performed with case identification through Natural language processing with Deep6 AI to identify all patients with endometrial cancer and bone metastasis at our institution between 2010 and 2020. Patient demographics, stage, grade, timing of metastasis and other characteristics were recorded. Standard statistical analyses were used to analyze the data. Twelve patients who met study inclusion were identified. The median age at initial diagnoses was 61 years. Two patients (16%) were diagnosed with brain metastasis at initial diagnosis of EC. Patients were equally distributed between stage I, III and IV with 4 patients (33%) in each group. Histology divided between serous (41%) Endometrioid (41%) Dedifferentiated (8%) and Mixed (8%) at diagnosis. Of endometrioid tumors(n=5) all were grade II. Mismatch repair (MMR) status was available for 4 patients (33%) patients and of those 1 was positive for MLH1 Mutation. In those patients who did not have brain metastasis present on initial diagnosis the median time from initial diagnosis to first location of recurrence was 24 months (Range 4-107 months) and to brain metastasis was 41 months (Range 4-140 months). Of those patients who had recurrent disease then progressed to brain metastasis, the median time from initial recurrence to brain metastasis was 25.5 months (Range 4-116 months). Other locations of recurrence included bone, lungs, liver, and mediastinum. Treatment for the brain metastasis varied widely but the most common was radiation which was included in the therapy of 77% of those treated. 22% had surgery which was combined with radiation or other systemic therapy. One patient with leptomeningeal disease was treated with intrathecal methotrexate. [Display omitted] Patients with brain metastasis from endometrial cancer tend to have higher grade and stage tumors at initial diagnosis. They have varying histology, presenting stage, and time to recurrence. Time of progression of initial non-brain recurrence to brain metastasis varies greatly. Further study is required to define patterns and timing of recurrence so treatment and counseling on risks can be optimized. [ABSTRACT FROM AUTHOR]

Tumor testing identified anaplastic lymphoma kinase gene rearrangements, and the patient was placed on crizotinib 250 mg orally twice daily for 20 weeks. Nagumo et al and Butrynski et al have reported cases that show drastic improvement in tumor size with use of crizotinib in patients with anaplastic lymphoma kinase rearrangement.2,3 Studies such as these have led the National Comprehensive Cancer Network to include crizotinib as standard treatment for patients with inflammatory myofibroblastic sarcomas and anaplastic lymphoma kinase rearrangements.4 Given the longevity of our patient and the success of others, we strongly encourage health care providers to perform fluorescence in situ hybridization testing of rare inflammatory myofibroblastic sarcomas to assess for anaplastic lymphoma kinase rearrangements. [Extracted from the article]

Study Design: Cadaveric biomechanical study. Objective: To determine fatigue behavior of cortical bone trajectory (CBT) pedicle screws. Summary Of Background Data: Cortical bone trajectory screws have been becoming popular in spine surgery; however, the long-term fatigue behavior of the new CBT screws remains understudied and limitations not well defined. Methods: Twelve vertebrae from six cadaveric lumbar spines were obtained. After bone mineral density (BMD) measurements, each vertebral body was instrumented with screws from each group, that is, CBT (4.5 × 25 mm) or standard pedicle screw (6.5 × 55 mm). A load (± 4 Nm sagittal bending) was applied under displacement control at 1 Hz. Each construct was loaded for 100 cycles or until 6° of loosening was observed. After fatigue testing, the screws were pulled out axially at 5 mm/min. Results: The standard pedicle screw showed better resistance against 100 cycle loading compared with the CBT screws (P < 0.001, 6.9° ± 4.8° vs. 15.2° ± 5.5°, respectively). The standard pedicle screw testing usually required more than 100 cycles of loading to achieve the critical loosening (3592 ± 4564 cycles), whereas the CBT screw never exceeded 100 cycles (84 ± 24 cycles) (P = 0.002). Increased BMD was significantly associated with a higher number of cycles and less loosening. The standard pedicle screw group had a higher postfatigue pullout load than the CBT screw group (P = 0.001, 776 ± 370 N and 302 ± 232 N, respectively). Conclusion: The standard pedicle screw had a better fatigue performance compared with the CBT screw in vertebra with compromised bone quality. The proper insertion of the CBT screw might be prevented by the laminar anatomy depending on the screw head design. The CBT screw damaged the bone along its shaft by rotating around a fulcrum, located at either the pars, pedicle isthmus, or the junction of the pedicle and superior endplate, contingent upon the strength of the bone. [ABSTRACT FROM AUTHOR]