Implementation of endometrial cancer molecular subtyping into a hybrid community-academic practice.

OBJECTIVES: We sought to confirm utility of our institution's modified Proactive Molecular Risk Classifier for Endometrial Cancer protocol in our daily practice, which includes mismatch repair (MMR), p53, and L1 cell adhesion molecule (L1CAM) immunohistochemistry with in-house next-generation sequencing for POLE, TP53, and CTNNB1. METHODS: We conducted a retrospective review of all patients in our institution who underwent primary endometrial carcinoma resection from the year prior to protocol implementation (PRE; October 1, 2020, to September 30, 2021) through first year of implementation (POST; October 1, 2021, to September 30, 2022) to compare the distribution of molecular and traditional staging factors using GOG-249 criteria to assign clinical risk. RESULTS: In total, 136 of 260 PRE patients were classified as clinically low risk (LR), of whom 31 were MMR deficient. Of the 157 LR POST patients with endometrioid-type carcinoma, 45 were MMR deficient, 5 were POLE mutant, 5 were TP53 mutant, 56 were of no specific molecular profile (NSMP), and 46 did not receive full protocol testing. Of all 79 POST NSMP endometrioid-type cases, 18 were CTNNB1 mutated and 8 showed L1CAM expression. CONCLUSIONS: Our protocol identified 22 (14%) of 157 LR tumors that harbored incipient intermediate- to high-risk molecular aberrations in TP53, CTNNB1, or L1CAM. Moving forward, results of ongoing trials assessing adjuvant therapy decisions based on molecular classification are necessary to confirm protocol utility and identify appropriate modifications.

Robot-assisted versus laparoscopic minimally invasive surgery for the treatment of stage I endometrial cancer.

OBJECTIVE: Recent reports in both cervical and endometrial cancer suggest that minimally invasive surgery (MIS) had an unanticipated negative impact on long-term clinical outcomes, including recurrence and death. Given increasing use of robotic surgery since the LAP2 trial, we sought to compare the intermediate and long-term outcomes between those who underwent robotic surgery or laparoscopy for Stage I endometrial cancer. METHODS: We performed a retrospective review of patients from a single, large, academic, urban practice who underwent either laparoscopic or robot-assisted MIS (RA-MIS) for the treatment of endometrial carcinoma between 2006 and 2016, ensuring at least 5 years of potential follow-up. To adjust for differences in confounding variables between groups, propensity score-based inverse probability of treatment weighting (IPTW) was performed. Overall and recurrence-free survival were compared using Cox proportional hazards regression models adjusting for confounding weights. RESULTS: 1027 patients were included; 461 received laparoscopy and 566 received RA-MIS. RA-MIS use increased steadily during the study window, which resulted in longer mean surveillance in laparoscopy group (median 8.7 years versus 6.3 years, p < 0.001). RA-MIS was associated poorer recurrence-free (HR: 1.41, 95% CI: 1.12, 1.77) and overall survival (HR: 1.39, 95% CI: 1.06, 1.83). Disease-specific survival was also poorer in the RA-MIS group (HR: 3.51, 95% CI: 2.19, 5.63). Among those who recurred, median time to first recurrence was shorter in the RA-MIS group than the laparoscopy group (16.3 vs. 28.7 months, p = 0.07). CONCLUSION: RA-MIS was associated with poorer long-term patient outcomes. Our data in this lower-risk population indicate relevant clinical endpoints may be occurring during intermediate and long-term follow-up windows. These findings support a prospective evaluation of the long-term outcomes of RA-MIS.

Cross-sectional study of psychosocial well-being among lesbian, gay, bisexual, and heterosexual gynecologic cancer survivors.

BACKGROUND: Delays in care and increased risk for mental health diagnoses put individuals identifying as a sexual minority with cancer at risk for decreased quality of life. AIM: To assess psychosocial health among sexual minority gynecologic cancer survivors, we compared self-reported quality of life and psychosocial measures between individuals diagnosed with gynecologic cancers identifying as lesbian/gay/bisexual (LGB) and heterosexual. METHODS AND RESULTS: English-speaking adults with gynecologic cancers were invited to participate in an ongoing cohort survey study. Quality of life and psychosocial measures included the Functional Assessment of Cancer Therapy-General, Distress Thermometer (distress), Patient Health Questionnaire-8 (depression), General Anxiety Disorder-7 (anxiety), and Post-traumatic Stress Disorder Checklist for DSM-5 (post-traumatic stress disorder; PTSD). Measures were compared by self-reported sexual orientation (heterosexual vs. LGB) using descriptive statistics (frequencies and means) and linear and logistic regression models, adjusting for college education. Of 814 patients invited, 457 enrolled (56.1%) and 401 (92.6%) completed the survey and provided information on their sexuality. All but one self-identified as cisgender women and 22 (5.5%) as LGB. LGB participants were more likely to have completed college (68.2% vs. 40.1%, p = .009) but were otherwise similar across demographic and clinical characteristics. Quality of life and distress scores were similar between groups. LGB participants, compared to heterosexual, reported higher rates of depression (31.8% vs. 10.6%, adjusted odds ratio [OR] = 4.1 [95% confidence interval [CI]: 1.6-11.0], p = .004), anxiety (25.0% vs. 7.1%, adjusted OR = 5.4 [95% CI: 1.7-16.7], p= .004), and PTSD (13.6% vs. 3.5%, adjusted OR = 4.2 [95% CI: 1.1-16.3], p = .04). CONCLUSION: LGB participants reported poorer emotional health following a gynecologic cancer diagnosis than heterosexual participants. Our data suggest this population may need additional resources and support during and after their cancer diagnosis. Future work is needed to identify additional risk factors and the underlying sources of these disparities in order to improve patient care and wellness in this population.

Sentinel Nodal Metastasis Detection in Endometrial Carcinoma With Microcystic, Elongated, and Fragmented (MELF) Pattern by Cytokeratin Immunostaining.

OBJECTIVES: The microcystic, elongated, and fragmented (MELF) pattern of myoinvasion in endometrial carcinoma (EC) is associated with an increased risk of lymph node metastasis. Our aim is to assess the role of cytokeratin immunohistochemical (IHC) stains in detecting sentinel nodal metastasis in MELF pattern tumors. METHODS: We recovered 19 MELF pattern EC hysterectomies with lymphadenectomy from our files. Negative nodes were subjected to cytokeratin AE1/AE3 IHC. Ten additional cases with sentinel lymph node (SLN) biopsies primarily assessed by IHC were also analyzed. RESULTS: Of the 19 cases of EC, 6 had positive lymph nodes based on H&E-stained sections at the time of their initial diagnosis. With the addition of IHC stains, 8 previously negative cases were found to have node metastases, and 3 of these were SLNs. Among the 10 cases primarily assessed by IHC, 5 had malignant cells in their SLNs. CONCLUSIONS: Cytokeratin IHC staining detected malignant cells in 9 of 16 cases with SLNs in our sample of women with MELF pattern of myoinvasion. Immunohistochemical stains should be routinely performed on SLNs from all MELF-positive cases to detect occult lymph node metastases and isolated tumor cells.

Spontaneous Transvaginal Sigmoid Colon Evisceration and Sepsis From Complete Procidentia.

BACKGROUND: Transvaginal bowel evisceration is an exceptionally rare event. Most reported cases are of small bowel evisceration in postmenopausal women who have undergone hysterectomy. CASE: Here, we report an isolated case of complete procidentia and spontaneous sigmoid colon evisceration leading to sepsis in an 89-year-old woman with no surgical history. CONCLUSIONS: We highlight the risk factors, clinical presentation, and treatment options for this unique multidisciplinary emergency.

Insights into the structure and function of ciliary and flagellar doublet microtubules: tektins, Ca2+-binding proteins, and stable protofilaments.

Cilia and flagella are conserved, motile, and sensory cell organelles involved in signal transduction and human disease. Their scaffold consists of a 9-fold array of remarkably stable doublet microtubules (DMTs), along which motor proteins transmit force for ciliary motility and intraflagellar transport. DMTs possess Ribbons of three to four hyper-stable protofilaments whose location, organization, and specialized functions have been elusive. We performed a comprehensive analysis of the distribution and structural arrangements of Ribbon proteins from sea urchin sperm flagella, using quantitative immunobiochemistry, proteomics, immuno-cryo-electron microscopy, and tomography. Isolated Ribbons contain acetylated α-tubulin, ß-tubulin, conserved protein Rib45, >95% of the axonemal tektins, and >95% of the calcium-binding proteins, Rib74 and Rib85.5, whose human homologues are related to the cause of juvenile myoclonic epilepsy. DMTs contain only one type of Ribbon, corresponding to protofilaments A11-12-13-1 of the A-tubule. Rib74 and Rib85.5 are associated with the Ribbon in the lumen of the A-tubule. Ribbons contain a single ∼5-nm wide filament, composed of equimolar tektins A, B, and C, which interact with the nexin-dynein regulatory complex. A summary of findings is presented, and the functions of Ribbon proteins are discussed in terms of the assembly and stability of DMTs, ciliary motility, and other microtubule systems.