Objective: The antitumor effects of anti-PD-1 antibody against mismatch repair deficiency (MMR-D)-associated cancers have been reported. MMR-D is found in approximately 20%–30% of endometrial carcinomas (ECs) and frequently occurs due to MLH1 promoter hypermethylation (MLH1-PHM). ECs with MLH1-PHM are classified according to the molecular screening of Lynch syndrome (LS), but few detailed reports are available. The purpose of this study was to clarify the clinical features of EC with MLH1-PHM. Methods: Immunohistochemistry of MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed on specimens from 527 ECs treated at our university hospital from 2003 to 2018. MLH1 methylation analysis was added to cases with MLH1/PMS2 loss. ECs were classified as follows: cases that retained MMR proteins as “MMR-proficient;” cases with MLH1/PMS2 loss and MLH1-PHM as “met-EC;” and cases with other MMR protein loss and MLH1/PMS2 loss without MLH1-PHM as “suspected-LS.” The clinical features, including long-term prognosis, of each group, were analyzed. Results: Accordingly, 419 (79.5%), 65 (12.3%), and 43 (8.2%) cases were categorized as “MMR-proficient,” “suspected-LS,” and “met-EC,” respectively. Significantly, “met-EC” had a lower proportion of grade 1 tumors (37.5%) and a higher proportion of stage III/IV tumors (37.2%) than the other groups. The overall and progression-free survival of “met-EC” were significantly worse than those of “suspected-LS” in all cases. Conclusion In ECs with MMR-D, “met-ECs” were a subgroup with a poorer prognosis than “suspected-LS.” “Met-ECs” would be the main target for anti-PD-1 antibody treatment, and its clinical susceptibility should be verified individually.

Objective: To investigate the effectiveness and safety of continuous infusion of midazolam for the treatment of headache and/or nausea/vomiting in patients with brain tumors or cancer-associated meningitis. Methods: Patients who presented with headache and/or nausea/vomiting and underwent continuous infusion of midazolam from April 2005 to March 2021 were retrospectively analyzed. Results: Among 22 patients, 19 presented with headache and 14 with nausea/vomiting. The success rate of continuous infusion of midazolam for headache was 89% and that for nausea/vomiting was 78%. The mean number of vomiting episodes within 24 hours from the start of midazolam administration was 0.14±0.36, which was significantly lower than that from 24 hours before to the start of administration (1.43±1.60, P=0.015). Sedation was observed as an adverse event in five (23%) patients, but no patients developed respiratory depression. Conclusion: When conventional therapies are ineffective for headache and/or nausea/vomiting caused by brain tumors or cancer-associated meningitis, continuous infusion of midazolam may improve symptoms and should be considered as a treatment option.