The role of second-look laparotomy in treatment of epithelial ovarian cancer

Forty-two patients underwent a second-look laparotomy to assess response to systemic chemotherapy for epithelial ovarian cancer. In 20 cases the operation showed no histologic evidence of disease. None of these cases received additional treatment at the time of negative second-look laparotomy. There has only been one recurrence noted in an average follow-up interval of 38.5 months. The remaining 22 cases did have residual carcinoma and 16 have developed progressive carcinoma despite secondary treatment. We found second-look laparotomy to be a safe and reliable assessment tool. However, we could not demonstrate a medical benefit from the procedure.     

A molecularly integrated grade for meningioma

BackgroundMeningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.MethodsWe evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.ResultsWe developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.ConclusionWe propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.     

Studies to elucidate the mechanism of fenarimol-induced infertility in male rats

Fenarimol (alpha-(2-chlorophenyl)-alpha-(4-chlorophenyl)-5- pyrimidinemethanol a pyrimidine carbinol fungicide, caused a dose-related decrease in male fertility in Wistar rats. The effect was particularly evident in the anatomically normal progeny of dams treated with fenarimol throughout gestation and lactation. Based on the observation that the infertility was associated with the absence of vaginal sperm at the time of mating, the effect appeared to be the result of an absence of male sexual behavior. Fenarimol does not readily cross the placenta but does concentrate in milk, reaching three- to fivefold higher concentrations than those observed in the maternal plasma. These results suggest that fenarimol might be acting to block the perinatal development of male patterns of sexual behavior which involves the action of gonadal steroids within the central nervous system (CNS). To test this hypothesis, [14C]fenarimol was administered to dams and the radioactivity measured in the brains of the neonates. Radioactivity in the hypothalamus was three- to fourfold higher and the half-life four times longer than that observed in the remainder of the brain. Since the hypothalamus is believed to play a key role in the development and expression of male sexual behavior, it appears likely that fenarimol is acting centrally to decrease male sexual behavior, thereby decreasing male fertility.     

A nucleic acid amplification test‐based strategy does not help inform return to work for healthcare workers with COVID‐19

ObjectiveThe objective of this study is to assess the utility of a nucleic acid amplification test‐based approach to shorten isolation of healthcare workers (HCWs) with COVID‐19 in the setting of the highly transmissible omicron variant.MethodsBetween December 24, 2021, and January 5, 2022, HCWs who tested positive for SARS‐CoV‐2 were retested with PCR at least 5 days since onset of symptoms.ResultsForty‐six sequential fully COVID‐19 vaccinated HCWs who had tested positive for SARS‐CoV‐2 underwent follow‐up testing. All the samples were confirmed as omicron variants and only four (8.7%) were negative in the follow‐up test performed at a median of 6 (range 5–12) since onset of symptoms.ConclusionsImplementation of a test‐based strategy is logistically challenging, increases costs, and did not lead to shorter isolation in our institution.     

Empowerment movements and mental health: Locus of control and commitment to the united farm workers

Psychologists in the community mental health field have contended that enhancement of psychological well-being is a likely benefit for individual participants in selfhelp, social-change-oriented organizations. This investigation sought to provide an empirical test of that proposition. A cross-section of 102 Mexican-American male seasonal farm workers who were differentially related to the United Farm Workers (Cesar Chavez, Director) were found to differ significantly on the I-E locus of control variable. It was possible to demonstrate a positive relationship for the participants between commitment (involvement) to the U. F. W. and an internal locus of control orientation (low perceived powerlessness).     

Children's understanding of their emotionally disturbed peers: A replication

Despite increasing recognition of the early importance of peer relations, virtually no systematic information exists on the way in which normal children view their emotionally disturbed peers. This paper reports a replication of recent findings on children's use of the concept of emotional disturbance. Ss were 40 fourth and sixth graders. Five vignettes that described one normal and four emotionally disturbed boys were read to individual Ss, who were interviewed about their understanding of the central figures (CFs). Interviews were coded to a 5-point scale of degree of perceived emotional disturbance. Earlier findings were replicated to a remarkable degree. Ss differentiated among the CFs in a manner congruent with clinician judges' ratings. Grade differences indicate the differential attention to and valuing of specific behaviors, rather than global differences in perception of emotional disturbance.     

ATR inhibition sensitizes liposarcoma to doxorubicin by increasing DNA damage

Liposarcomas account for approximately 20% of all adult sarcomas and have limited therapeutic options outside of surgery. Inhibition of ataxia-telangiectasia and Rad3 related protein kinase (ATR) has emerged as a promising chemotherapeutic strategy in various cancers. However, its activation, expression, and function in liposarcoma remain unkown. In this study, we investigated the expression, function, and potential of ATR as a therapeutic target in liposarcoma. Activation and expression of ATR in liposarcoma was analyzed by immunohistochemistry, which was further explored for correlation with patient clinical characteristics. ATR-specific siRNA and the ATR inhibitor VE-822 were applied to determine the effect of ATR inhibition on liposarcoma cell proliferation and anti-apoptotic activity. Migration activity and clonogenicity were examined using wound healing and clonogenic assays. ATR (p-ATR) was overexpressed in 88.1% of the liposarcoma specimens and correlated with shorter overall survival in patients. Knockdown of ATR via specific siRNA or inhibition with VE-822 suppressed liposarcoma cell growth, proliferation, migration, colony-forming ability, and spheroid growth. Importantly, ATR inhibition significantly and synergistically enhanced liposarcoma cell line chemosensitivity to doxorubicin. Our findings support ATR as critical to liposarcoma proliferation and doxorubicin resistance. Therefore, the addition of ATR inhibition to a standard doxorubicin regimen is a potential treatment strategy for liposarcoma.     

Neoadjuvant therapy and biliary decompression lower biliary and pancreatic juice vascular endothelial growth factor levels in patients with periampullary adenocarcinoma

Increased expression of vascular endothelial growth factor (VEGF) by pancreatic cancer correlates with poor survival. The significance of VEGF in biliary and pancreatic secretions in periampullary cancers is unknown. Bile and pancreatic juice samples were collected from patients undergoing pancreaticoduodenectomy (PD). All samples were frozen at -70 degrees C until subsequent analysis for VEGF concentration using enzyme-linked immunoabsorbent assay (ELISA). Plasma VEGF levels in pancreatic cancer patients were <10 pg/mL. The biliary VEGF concentration for patients with malignancy was significantly elevated compared to benign disease (P = 0.05). There was no difference in pancreatic VEGF concentrations between benign and malignant disease. Cancer patients undergoing preoperative chemoradiation (CRT) had lower biliary and pancreatic VEGF concentrations than those who did not. Preoperative biliary drainage (BD) was associated with decreased VEGF concentrations in bile (3500 pg/mL vs 7740 pg/mL, P = 0.027). Patients undergoing both CRT and BD had diminished biliary and pancreatic VEGF concentrations compared to those who had neither. This was statistically significant for pancreatic VEGF concentrations (917 pg/mL vs 4723 pg/mL, P = 0.044). VEGF is highly concentrated in bile and pancreatic juice compared to plasma. Preoperative CRT and BD significantly reduce these levels in patients with periampullary cancers. Antiangiogenic therapy aimed at interrupting the VEGF pathway appears to be a logical target in periampullary cancer.