MLH1/PMS2 loss due to epigenetic hypermethylation of the MLH1 promoter is the most common cause of mismatch repair deficiency in endometrial carcinoma, and typically provides reassurance against an associated germline mutation. To further characterize the genetic features of MLH1/PMS2-deficient endometrial cancers, the departmental database was searched for cases with dual MLH1/PMS2 loss and retained MSH2/6 expression which underwent MLH1 hypermethylation testing. Genetic testing results were obtained when available. One hundred seventeen endometrial cancers met inclusion criteria 100 (85%) were MLH1-hypermethylated, 3 (3%) were low-level/borderline, 7 (6%) were nonmethylated, and 7 (6%) were insufficient for testing. Sixteen cases (12 MLH1-hypermethylated, 3 nonmethylated, and 1 insufficient for testing) underwent germline testing, 6 of which (37.5%) demonstrated germline variants of unknown significance (VUS) (MSH6, PMS2, POLD1, BRIP1, RAD51D, CHEK2) but no known deleterious mutations. Notably, however, the patients harboring the MSH6 and PMS2 germline VUS had clinical features concerning for Lynch syndrome. One nonmethylated, germline-normal case underwent somatic tumor testing, and demonstrated a somatic MLH1 mutation. In summary, MLH1-hypermethylation accounts for the vast majority of MLH1/PMS2-deficient cancers in a universally screened population, although MLH1 somatic and germline mutations can occur. Occasionally, patients with MLH1-hypermethlated tumors also bear germline VUS in other mismatch repair genes as well as genes implicated in other hereditary cancer syndromes, but their clinical relevance is unclear. Family and personal cancer histories must always be evaluated to determine the need for germline testing in women with loss of MLH1/PMS2, even in the setting of hypermethylation.Only a few cases of malignant peritoneal mesothelioma (MPeM) associated with endometriosis have been published; with chronic inflammation of the peritoneum associated with the latter being postulated as an inducing factor in the pathogenesis of this tumor. We assessed the clinicopathologic characteristics of MPeM associated with endometriosis to determine if there were other factors besides inflammation that may contribute to the pathogenesis in this patient population. Fifteen MPeM associated with endometriosis were retrieved from our files. Most presented with abdominal/pelvic pain, mass or distention; median age was 45 yr. Only 16% of patients had a history of asbestos exposure. In contrast, a third of the patients had a personal history of other neoplasms, and >80% had a family history of malignancies. Although most tumors had gross and microscopic features typical of MPeM, some had confounding features including “adhesion-like” appearance or gelatinous cysts/nodules, and signet ring cells. Tumors were epithelioid (9) and biphasic (6). MPeM was misdiagnosed as Müllerian carcinoma in 40% of cases. All patients (n=15) had cytoreductive surgery in addition to other therapies. Only 2/12 patients died of disease (17%). The 3- and 5-yr overall survival was 90%. MPeM associated with endometriosis tends to occur in patients with personal/familial history of malignancies, which may be a predisposing factor. In light of this finding, the role of endometriosis in the pathogenesis of MPeM is likely less relevant. The favorable outcome seen in these patients may be related to germline mutations or the hormonal milieu and needs further investigation.

Although indoor monitoring of radon and benchmarking of radon measurement devices remain important research topics, few intercomparisons of active radon measurement devices have been performed under realistic conditions, let alone dynamic ones enabling comparison of their transient behavior. Five different radon monitors were therefore placed in a poorly ventilated basement space under three different conditions 24 h under a steady, elevated radon level, 24 h with fans turned on to produce a radon washout transient, and 9 d with fans turned off for a radon buildup transient. Resulting radon concentrations varied between ~200 and ~2,000 Bq m-3. Accuracy of the devices were evaluated using root-mean-square error, and ventilation data were fit to first order linear compartmental models. To more accurately model behaviors such as cyclic diurnal variations, the source term corresponding to entry of radon from soil into the basement was considered to be non-constant, as it is likely to vary drastically with both to first order linear compartmental models. To more accurately model behaviors such as cyclic diurnal variations, the source term corresponding to entry of radon from soil into the basement was considered to be non-constant, as it is likely to vary drastically with both the indoor-outdoor pressure differential and soil concentration variations. The improved radon washout model fit very well with the measurements. Despite a wide variety in list prices, all devices performed similarly during transients and at different radon concentrations.

In the nuclear industry, wound contamination with americium is expected to increase with decommissioning and waste management. Treatment of workers with diethylenetriaminepentaacetic acid (DTPA) requires optimization to reduce internal contamination and radiation exposure. This work aimed at evaluating and comparing different DTPA protocol efficacies after wound contamination of rats with americium. Wound contamination was simulated in rats by depositing americium nitrate in an incision in the hind limb. selleck compound Different routes, times, and frequencies of DTPA administration were evaluated. Individual daily urinary americium excretion and tissue retention were analyzed using the statistical tool STATBIODIS. Urinary profiles, urinary enhancement factors, and inhibition percentages of tissue retention were calculated. A single DTPA administration the day of contamination induced a rapid increase in americium urinary excretion that decreased exponentially over 7 d, indicating that the first DTPA administration should ous injections were equally effective. Inherent difficulties in wound site activity measurements did not allow identification of a significant decorporating effect at the wound site. Repeated intravenous injections of DTPA also increased americium urinary excretion, which supports the use of multiple DTPA administrations shortly after wound contamination. Results from these statistical analyses will contribute to a better understanding of americium behavior in the presence or absence of DTPA and may aid optimization of treatment for workers.