Long-term disease-free survival with chemotherapy and pembrolizumab in a patient with unmeasurable, advanced stage dedifferentiated endometrial carcinoma.

Dedifferentiated endometrial carcinoma is a rare, highly aggressive subtype of endometrial cancer associated with poor survival outcomes. Current guidelines recommend treatment of advanced-stage disease with surgical staging or cytoreduction and platinum/taxane-based chemotherapy. Despite these approaches, the achievement of long-term remission or prolonged survival is challenging. Recent Phase III studies demonstrate that the addition of PD-1 inhibitors to standard chemotherapy significantly improves progression-free survival in patients with measurable, mismatch repair deficient (dMMR) and proficient (pMMR) advanced-stage or recurrent endometrial carcinoma. However, the role of PD-1 blockade in the treatment of undifferentiated and dedifferentiated endometrial carcinoma remains unclear, as very few patients with these cancer subtypes were included in the trials. In this case report, we present a patient with dMMR dedifferentiated endometrial carcinoma, treated with primary surgery to no gross residual disease, followed by carboplatin/paclitaxel chemotherapy and a short course of maintenance pembrolizumab. To date, the patient remains with a prolonged disease-free survival of 61 months, supporting the potential use of PD-1 inhibitors in the upfront treatment of unmeasurable, advanced-stage, dMMR dedifferentiated endometrial carcinoma.

Overweight and obese women's symptoms, knowledge, and preferences regarding endometrial biopsy for endometrial cancer detection: A threshold technique survey.

Background: The incidence of endometrial cancer (EC) in the United States continues to rise, driven mainly by the obesity epidemic. We sought to determine overweight and obese women's cancer risk knowledge and preferences regarding diagnostic endometrial biopsy (EMB) for EC detection. Methods: An online survey was administered to overweight and obese women without EC recruited through the electronic medical record's online patient portal. Baseline questions queried gynecologic history, cancer risk knowledge, and factors potentially influencing decision-making for EMB. We used the threshold survey technique to identify the minimum acceptable risk (MAR) threshold at which each respondent would be willing to undergo an EMB to detect EC. Results: Of 357 respondents (median age 45 years (interquartile range [IQR]: 38-54); median BMI 39 [IQR: 36.0-44.6]), fewer than half (48.7 %) were aware that obesity is a risk factor for EC, and 10 % considered their risk of EC to be high. Almost half (42 %) of respondents reported MAR thresholds characterized as very low (0-1 %), and these were more common among respondents with higher BMIs. Forty percent identified their weight as a factor influencing their MAR threshold decision, while 76 % identified their perceived personal risk as a factor. Less than half cited immediate risks of the procedure. Conclusion: Many patients reported being willing to undergo an EMB at very low risk thresholds for EC. Perceived personal risk is a stronger factor in decision-making than immediate procedural risks. Providers should focus on communicating patients' risk to motivate EMB to detect EC where appropriate.

Case report: prolonged durable clinical benefit and low toxicity from combination endocrine therapy in a patient with recurrent endometrial carcinoma.

Background: Endometrial carcinoma is the most common gynecologic cancer, with increasing incidence and mortality. Combination endocrine therapy comprised of tamoxifen and progestational agents has demonstrated promising results in treating recurrent disease. This case report describes the prolonged clinical benefit of treatment with tamoxifen and megestrol acetate in a woman with recurrent, metastatic endometrial endometrioid carcinoma positive for estrogen (ER) and progesterone receptors (PR). Case: A 71-year-old gravida 1 para 1 woman presented with postmenopausal bleeding and vaginal discharge. Pelvic ultrasound and magnetic resonance imaging confirmed a 4.7 cm endometrial mass. The patient underwent a total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, and cystoscopy; pathology revealed a FIGO stage IA grade 1 ER/PR-positive endometroid endometrial adenocarcinoma. She continued under active surveillance for approximately 42 months until she experienced bone metastases in her pelvis, for which she received radiation therapy. Five months later, pulmonary metastases were detected, and she received six cycles of carboplatin and paclitaxel. She then started megestrol acetate and tamoxifen and has remained clinically stable with minimal side effects and reasonable quality of life for approximately 57 months. Conclusion: Our case suggests that combination endocrine therapy has the potential to provide substantial long-term clinical benefit in women with recurrent endometrial cancer and bone metastases, despite multiple prior treatments, allowing patients to experience stable disease and quality of life. In patients with recurrent endometrioid, ER/PR-positive disease, endocrine therapy alone or in combination with other targeted therapies are regimens that may be considered due to their low overall toxicity.

Impact of enhanced recovery after surgery (ERAS) protocol on gastrointestinal function in gynecologic oncology patients undergoing laparotomy.

OBJECTIVE: To evaluate the impact of enhanced recovery after surgery (ERAS) on postoperative gastrointestinal function in gynecologic oncology patients. METHODS: This retrospective cohort study compared gynecology oncology patients undergoing non-emergent laparotomy from 10/2016 to 6/2017 managed on an ERAS protocol to a control cohort from the year prior to ERAS implementation. Major changes to postoperative care after ERAS implementation included multimodal analgesia, early feeding, goal-directed fluid resuscitation, and early ambulation. The primary outcome was rate of postoperative ileus, defined as nausea and vomiting requiring nothing-per-mouth status or nasogastric tube (NGT) placement. Secondary outcomes included length of stay (LOS) and 30-day readmission. RESULTS: 376 patients met inclusion criteria; 197 in the control group and 179 in the ERAS group. Patient demographics were similar between groups. Ileus rate was significantly lower in the ERAS group (2.8% vs. 15.7%; p < 0.001), and fewer patients in the ERAS group required NGT placement (2.2% vs. 7.1%; p = 0.06). ERAS remained independently associated with decreased ileus rates when controlling for other patient and surgical factors (OR 0.2; p = 0.01). Epidural use was correlated with a significant increase in ileus risk (OR 2.6; p = 0.03), as was increased Charlson Comorbidity Index (OR 1.2; p < 0.01). LOS was significantly decreased in the ERAS group (2.9 vs. 4.0 days; p = 0.04), while 30-day readmission rates were similar (10.1% vs. 10.7%; p = 0.62). CONCLUSIONS: Implementation of an ERAS protocol significantly decreases the risk of postoperative ileus in gynecologic oncology patients undergoing laparotomy. ERAS also reduced LOS compared to pre-ERAS controls.

Leaf shape evolution has a similar genetic architecture in three edaphic specialists within the Mimulus guttatus species complex.

BACKGROUND AND AIMS: The genetic basis of leaf shape has long interested botanists because leaf shape varies extensively across the plant kingdom and this variation is probably adaptive. However, knowledge of the genetic architecture of leaf shape variation in natural populations remains limited. This study examined the genetic architecture of leaf shape diversification among three edaphic specialists in the Mimulus guttatus species complex. Lobed and narrow leaves have evolved from the entire, round leaves of M. guttatus in M. laciniatus, M. nudatus and a polymorphic serpentine M. guttatus population (M2L). METHODS: Bulk segregant analysis and next-generation sequencing were used to map quantitative trait loci (QTLs) that underlie leaf shape in an M. laciniatus × M. guttatus F2 population. To determine whether the same QTLs contribute to leaf shape variation in M. nudatus and M2L, F2s from M. guttatus × M. nudatus and lobed M2L × unlobed M. guttatus crosses were genotyped at QTLs from the bulk segregant analysis. KEY RESULTS: Narrow and lobed leaf shapes in M. laciniatus, M. nudatus and M. guttatus are controlled by overlapping genetic regions. Several promising leaf shape candidate genes were found under each QTL. CONCLUSIONS: The evolution of divergent leaf shape has taken place multiple times in the M. guttatus species complex and is associated with the occupation of dry, rocky environments. The genetic architecture of elongated and lobed leaves is similar across three species in this group. This may indicate that parallel genetic evolution from standing variation or new mutations is responsible for the putatively adaptive leaf shape variation in Mimulus.

Diabetes connect: African American men's preferences for a community-based diabetes management program.

PURPOSE: The purpose of the study is to explore African American men's perceptions of how community-based, community-health worker (CHW)-delivered diabetes interventions might best be implemented. METHODS: Four 90-minute focus groups were guided by a trained moderator with a written guide to facilitate discussion on the topic of diabetes management and preferences for community-based programs. Participants were recruited from the diabetes education database at a safety-net health system in Jefferson County, AL. Two independent reviewers performed content analysis to identify major themes using an iterative, combined deductive and inductive approach. RESULTS: There were 25 male participants. Mean years living with diabetes was 9.6 (range, 1-20). Participants demonstrated knowledge of self-management strategies and identified various hardships including emotional and physical manifestations of diabetes, dietary restrictions, and institutional frustrations with the health system that contributed to self-management barriers. Their preferred CHW responsibilities were to educate, hold support groups, help track daily activities, and help find resources. Potential concerns included the need for confidentiality and fears of being stereotyped. CONCLUSIONS: Participants identified critical self-management strategies but endure hardships that present barriers to daily diabetes management. Preferences for community-based programs and suggested CHW responsibilities could help to overcome many of those barriers by increasing access and providing support.