Context-dependent environmental associations with endometrial cancer histotype and genotype.

OBJECTIVE: MLH1 loss due to MLH1 methylation, detected during Lynch syndrome screening, is one of the most common molecular changes in endometrial cancer. It is well established that environmental influences such as nutritional state can impact gene methylation, both in the germline and in a tumor. In colorectal cancer and other cancer types, aging is associated with changes in gene methylation. The objective of this study was to determine if there was an association between aging or body mass index on MLH1 methylation in sporadic endometrial cancer. METHODS: A retrospective review of patients with endometrial cancer was performed. Tumors were screened for Lynch syndrome via immunohistochemistry, with MLH1 methylation analysis performed when there was loss of MLH1 expression. Clinical information was abstracted from the medical record. RESULTS: There were 114 patients with mismatch repair deficient tumors associated with MLH1 methylation, and 349 with mismatch repair proficient tumors. Patients with mismatch repair deficient tumors were older than those whose tumors were proficient. Mismatch repair deficient tumors had a higher incidence of lymphatic/vascular space invasion. When stratified by endometrioid grade, associations with body mass index and age became apparent. Patients with endometrioid grades 1 and 2 tumors and somatic mismatch repair deficiency were significantly older, but body mass index was comparable with that of the mismatch repair intact group. For endometrioid grade 3, patient age did not significantly vary between the somatic mismatch repair deficient group and the mismatch repair intact group. In contrast, body mass index was significantly higher in the patients with grade 3 tumors with somatic mismatch repair deficiency. CONCLUSION: The relationship of MLH1 methylated endometrial cancer with age and body mass index is complex and somewhat dependent on tumor grade. As body mass index is modifiable, it is possible that weight loss induces a 'molecular switch' to alter the histologic characteristics of an endometrial cancer.

Dispensing and Purchasing Antibiotics Without Prescription: A Cross-sectional Study Among Pharmacists and Patients in Beirut, Lebanon.

Antimicrobial resistance is a global public health issue, exacerbated by dispensing and purchasing antibiotics without a prescription, common in low- and middle-income countries, such as Lebanon. This study aimed to (1) describe behavioral patterns underpinning dispensing and purchasing antibiotics without a prescription among pharmacists and patients, (2) describe reasons for, and (3) attitudes toward these behaviors. A cross-sectional study targeted pharmacists and patients, respectively, identified through stratified random sampling and convenience sampling from all 12 Beirut quarters. Questionnaires assessed behavioral patterns, reasons for, and attitudes toward dispensing and purchasing antibiotics without prescription among the 2 samples. A total of 70 pharmacists and 178 patients were recruited. About a third (37%) of pharmacists supported dispensing antibiotics without a prescription, considering it acceptable; 43% of patients report getting antibiotics without a prescription. Reasons for distributing and purchasing antibiotics without prescription include financial costs associated with the drugs and convenience, coupled with inexistent law enforcement. Dispensing antibiotics without prescription was shared among a relatively high proportion of pharmacists and patients residing in Beirut. Dispensing antibiotics without prescription is common in Lebanon, where law enforcement needs to be stronger. National efforts, including anti-AMR campaigns and law enforcement, must be rapidly implemented to avoid the double disease burden, especially when old and new vaccines are available, and superbugs are making preventative public health efforts more difficult.

Molecular Characterizations of Gynecologic Carcinosarcomas: A Focus on the Immune Microenvironment.

Gynecologic carcinosarcomas, specifically of endometrial and ovarian origin, are aggressive and rare tumors. Treatment data are limited and are often extrapolated from other histologies and smaller retrospective studies. While the optimal therapy approach remains contentious, treatment is often multimodal and may include surgery, chemotherapy, radiation, or a combination of multiple strategies. However, despite aggressive treatment, these tumors fare worse than carcinomas of the same anatomic sites irrespective of their stage. Recent studies have described in-depth molecular characterizations of gynecologic carcinosarcomas. Although many molecular features mirror those seen in other uterine and ovarian epithelial tumors, the high prevalence of epithelial-mesenchymal transition is more unique. Recently, molecular descriptions have expanded to begin to characterize the tumor immune microenvironment. While the importance of the immune microenvironment has been well-established for other tumor types, it has been less systematically explored in gynecologic carcinosarcomas. Furthermore, the use of immunotherapy in patients with gynecologic carcinosarcomas has not been extensively evaluated. In this review, we summarize the available data surrounding gynecologic carcinosarcomas, with a focus on the immune microenvironment. We end with a discussion of potential immunotherapy uses and future directions for the field.