FGFR2c Mesenchymal Isoform Expression Is Associated with Poor Prognosis and Further Refines Risk Stratification within Endometrial Cancer Molecular Subtypes.

PURPOSE: The two most common molecular subtypes of endometrial cancers, mismatch repair deficient (MMRd) and p53 wild-type (p53wt) comprise the majority of endometrial cancers and have intermediate prognoses where additional risk stratification biomarkers are needed. Isoform switching of FGFR2 from FGFR2b to FGFR2c (normally expressed in mesenchymal cells), has been reported in other solid carcinomas. The objective of this study was to investigate the role of FGFR2c in risk stratification of endometrial cancer. EXPERIMENTAL DESIGN: We have developed and optimized a BaseScope RNA ISH assay to detect FGFR2c. FGFR2c expression was determined in a preliminary screening cohort of 78 endometrial cancers and a clinically and molecularly annotated Vancouver cohort (n = 465). Cox regression model analyses were performed to assess the prognostic value of FGFR2c. RESULTS: Univariate and multivariate analyses revealed FGFR2c expression was significantly associated with shorter disease-specific survival (DSS) and progression-free survival (PFS) in endometrioid endometrial cancer (EEC, n = 302). Notably, FGFR2c expression was significantly associated with shorter PFS and DSS in patients with grade 3 EECs (P < 0.003 and P < 0.002) and the European Society Medical Oncology (ESMO) high-risk group (P < 0.0001 and P < 0.002), respectively. Moreover, within the MMRd subtype, FGFR2c expression was significantly associated with shorter PFS (P < 0.048) and DSS (P < 0.001). CONCLUSIONS: FGFR2c expression appears an independent prognostic biomarker in patients with EEC and further discerns the outcomes within grade 3 tumors, ESMO high-risk groups, as well as within the MMRd and p53wt subtypes. FGFR2c inclusion into future molecular subtyping can further refine risk stratification of EEC.

Reduction of adverse drug events and medication errors in a community hospital setting.

Keys to success in reducing ADEs have included the support of administrative leaders through their visibility and emphasis on safety as an organizational priority, and financial support for safety projects. Administrative participation was also helpful in promoting safety efforts through the reinforcement of expectations when progress was sluggish. The use of rapid cycle change provided enough early success to serve in motivating staff to push ahead. It allowed staff the opportunity to analyze changes, make adjustments, and retest on a slightly larger scale. Other key success factors included the motivation of teams through continual sharing of progress and success stories; celebrations for achievements are held routinely. As an organization, SJMC has shared its success strategies with other organizations and promoted networking with other organizations to determine what strategies have worked elsewhere. This is helpful as it prevents time from being wasted on solutions that have been tried without success. Within the OSF Healthcare System, the following phrase has been adopted in regard to patient safety, "Safety is like peeling an onion; the more you look, the more you find, and each layer makes you cry."

Somatization Disorder in Elderly Patients.

Little is known about the prevalence, characteristics, or natural history of somatization disorder in elderly patients. The authors evaluated 353 adult women (from outpatient psychiatric and medical clinics) for somatization disorder. Twenty-four percent of patients were 55 years old or older. The sample of older women did not differ from younger women in the proportion who were positive for somatization disorder, the number of somatic symptoms, or characteristics of the disorder. The authors compare these findings with prior literature and make suggestions for future prospectively designed studies.

Patient safety.

Patient safety is a cause for concern among health care providers, payers, employers, policy makers, and the general public. But it is difficult for most case managers to get their arms around what they can do about patient safety in hospitals. This article discusses the patient safety movement in this country and defines the vital role case managers can play in making health care safer for patients. It describes the changing case manager challenges and competencies needed to meet these challenges.

Intermediate term biochemical progression rates after radical prostatectomy and radiotherapy in patients with screen detected prostate cancer.

PURPOSE: We compared biochemical progression rates measured by increasing prostate specific antigen (PSA) levels using a standard definition of biochemical recurrence among patients with screen detected prostate cancer treated with radical prostatectomy (RP) or radiotherapy (RT). MATERIALS AND METHODS: A total of 1,939 patients diagnosed with clinically localized prostate cancer in a community based screening study from 1989 to 1998, followed through 2001, were treated with RP or RT and agreed to enroll in a followup study. This prospective cohort study (median followup 62 months, range 0.2 to 141) used adjusted Cox proportional hazards models to examine time to progression. Selection bias was addressed with propensity scores. Biochemical evidence of cancer progression was defined as PSA greater than 0.2 ng/ml in patients who underwent RP and 3 consecutive PSA increases as recommended by the American Society for Therapeutic Radiology and Oncology criteria for radiotherapy. RESULTS: Of the patients 17% had evidence of cancer progression. The percentage with progression-free survival at 5 and 9 years for RP was 84% and 76%, respectively, and for RT 80% and 70%, respectively. Cox proportional hazards models produced a hazard ratio of 1.63 (95% CI, 1.12, 2.38) for RT compared with RP, adjusting for clinical stage, Gleason grade, preoperative PSA, biopsy age, treatment year and propensity for treatment type. CONCLUSIONS: With intermediate term followup, patients treated with RT were more likely to have cancer progression than with RP adjusting for demographics, clinical factors, selection bias and treatment year.

Patient preferences for outcomes associated with surgical management of prostate cancer.

PURPOSE: We used utility assessment to evaluate patient preferences for current urinary and sexual function after radical prostatectomy. MATERIALS AND METHODS: We measured preferences in 209 community volunteers enrolled in a prostate cancer screening study who underwent radical prostatectomy between 1994 and 1998. We compared preferences in 3 outcome groups, namely men bothered by current urinary and sexual functioning, only bothered by current sexual functioning and not bothered by current sexual or urinary functioning. Preferences were assessed via a computer based interview using time trade-off and standard gamble methods. Current functioning was assessed via a standardized questionnaire. RESULTS: Median time trade-off and standard gamble utilities were high at 0.9 across outcome groups, indicating that men were not willing to give up many remaining life years (10% of remaining life expectancy) with current functioning to achieve ideal functioning. However, mean time trade-off and standard gamble scores significantly decreased as the burden increased in men bothered by current sexual and urinary function (0.77 and 0.82), bothered by current sexual function only (0.87 and 0.89) and not bothered by sexual or urinary function (0.92 and 0.96, respectively). CONCLUSIONS: Health related quality of life was generally good in this observational study of patients treated for prostate cancer with radical prostatectomy. In addition, those bothered by urinary and/or sexual function would not be willing to trade much of the remaining life span to achieve perfect functioning. However, the perception of side effects was bothersome enough in some men to warrant appropriate patient counseling regarding the potential risks and benefits.

Prostate-specific antigen cutoff of 2.6 ng/mL for prostate cancer screening is associated with favorable pathologic tumor features.

OBJECTIVES: To evaluate the pathologic characteristics of clinical Stage T1c (nonpalpable, prostate-specific antigen [PSA]-detected) prostate cancers detected in the 2.6 to 4.0-ng/mL PSA range and compare them with Stage T1c cancers concurrently detected in the 4.1 to 10.0-ng/mL PSA range. All cancers were detected in a prostate cancer screening study. METHODS: We studied 94 patients with clinical Stage T1c prostate cancer diagnosed by four or six-sector ultrasound-guided needle biopsy who underwent radical prostatectomy between June 1995 and December 1996. We included all men whose prostatectomy specimens were processed with complete embedding of all prostatic tissue. Of these, 42 had a PSA level of 2.6 to 4.0 ng/mL and 52 a PSA level 4.1 to 10.0 ng/mL at the time of cancer detection. We determined the tumor volume by complete embedding and grid morphometry, pathologic stage, Gleason sum, and surgical margin status and compared the cancer volume and pathologic tumor stages for each group. RESULTS: Men with cancer detected at the 2.6 to 4.0 ng/mL PSA range had significantly smaller cancer volumes (1.1 +/- 1.1 cm(3) versus 1.8 +/- 1.5 cm(3), P = 0.02); however, no difference was found in the proportion (11.9% versus 11.5%, P = 0.9, and 23.8% versus 26.9%, P = 0.7, respectively) of tumors that met previously published criteria of "clinically insignificant" (organ confined, less than 0.2 cm(3) tumor volume, Gleason sum 6 or less) or "clinically unimportant" (organ confined, less than 0.5 cm(3) tumor volume, and Gleason sum 6 or less) tumors. Using the lower PSA cutoff point resulted in the detection of a significantly higher percentage of organ-confined tumors (88% versus 63%, P = 0.01). CONCLUSIONS: The use of a 2.6-ng/mL PSA threshold for screening resulted in the more frequent detection of small, organ-confined tumors without overdetecting possibly clinically insignificant ones.