Kathryn Osann

Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers

To compare the survival of women with uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CC) to those with grade 3 endometrioid uterine carcinoma (G3EC). Demographic, pathologic, treatment, and survival information were obtained from the Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Data were analysed using Kaplan–Meier and Cox proportional hazards regression methods. Of 4180 women, 1473 had UPSC, 391 had CC, and 2316 had G3EC cancers. Uterine papillary serous carcinoma and CC patients were older (median age: 70 years and 68 vs 66 years, respectively; P<0.0001) and more likely to be black compared to G3EC (15 and 12% vs 7%; P<0.0001). A higher proportion of UPSC and CC patients had stage III–IV disease compared to G3EC patients (52 and 36% vs 29%; P<0.0001). Uterine papillary serous carcinoma, CC and G3EC patients represent 10, 3, and 15% of endometrial cancers but account for 39, 8, and 27% of cancer deaths, respectively. The 5-year disease-specific survivals for women with UPSC, CC and G3EC were 55, 68, and 77%, respectively (P<0.0001). The survival differences between UPSC, CC and G3EC persist after controlling for stage I–II (74, 82, and 86%; P<0.0001) and stage III–IV disease (33, 40, and 54; P<0.0001). On multivariate analysis, more favourable histology (G3EC), younger age, and earlier stage were independent predictors of improved survival. Women with UPSC and CC of the uterus have a significantly poorer prognosis compared to those with G3EC. These findings should be considered in the counselling, treating and designing of future trials for these high-risk patients.

Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients.

The purpose of the current study was to determine the potential therapeutic role of lymphadenectomy in women with endometrioid corpus cancer.

A replication of the Autism Diagnostic Observation Schedule (ADOS) revised algorithms

OBJECTIVE To replicate the factor structure and predictive validity of revised Autism Diagnostic Observation Schedule algorithms in an independent dataset (N = 1,282). METHOD Algorithm revisions were replicated using data from children ages 18 months to 16 years collected at 11 North American sites participating in the Collaborative Programs for Excellence in Autism and the Studies to Advance Autism Research and Treatment. RESULTS Sensitivities and specificities approximated or exceeded those of the old algorithms except for young children with phrase speech and a clinical diagnosis of pervasive developmental disorders not otherwise specified. CONCLUSIONS Revised algorithms increase comparability between modules and improve the predictive validity of the Autism Diagnostic Observation Schedule for autism cases compared to the original algorithms.

Altered Innate Immune Functioning of Dendritic Cells in Elderly Humans: A Role of Phosphoinositide 3-Kinase-Signaling Pathway

Aging represents a state of paradox where chronic inflammation is associated with declining immune responses. Dendritic cells (DCs) are the major APCs responsible for initiating an immune response. However, DC functions in aging have not been studied in detail. In this study, we have compared the innate immune functions of monocyte-derived myeloid DCs from elderly subjects with DCs from young individuals. We show that although phenotypically comparable, DCs from the aging are functionally different from DCs from the young. In contrast to DCs from the young, DCs from elderly individuals display 1) significantly reduced capacity to phagocytose Ags via macropinocytosis and endocytosis as determined by flow cytometry; 2) impaired capacity to migrate in vitro in response to the chemokines MIP-3β and stromal cell-derived factor-1; and 3) significantly increased LPS and ssRNA-induced secretion of TNF-α and IL-6, as determined by ELISA. Investigations of intracellular signaling revealed reduced phosphorylation of AKT in DCs from the aging, indirectly suggesting decreased activation of the PI3K pathway. Because the PI3K-signaling pathway plays a positive regulatory role in phagocytosis and migration, and also functions as a negative regulator of TLR signaling by inducing activation of p38 MAPK, this may explain the aberrant innate immune functioning of DCs from elderly subjects. Results from real-time PCR and protein expression by flow cytometry demonstrated an increased expression of phosphatase and tensin homolog, a negative regulator of the PI3K-signaling pathway, in DCs from the aging. Increased phosphatase and tensin homolog may thus be responsible for the defect in AKT phosphorylation and, therefore, the altered innate immune response of DCs from elderly humans.

Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features

Background. Bronchioloalveolar lung carcinoma (BAC) is a unique type of lung cancer with distinguishing pathologic, biologic, epidemiologic, demographic, and perhaps etiologic features.

Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers

OBJECTIVE To compare the clinico-pathologic characteristics and survival of women with clear cell versus other epithelial ovarian cancers. METHODS Data were obtained from the Surveillance, Epidemiology and End Results Program between 1988 and 2001 and analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS Of 28,082 women with epithelial ovarian cancer, 1411 (5%) had clear cell, 13,835 (49.3%) papillary serous, 3655 (13%) endometrioid, 2711 (9.7%) mucinous, and 6470 (23%) had unspecified histologies. The median age of overall patients was 64 years; with clear cell patients presenting at younger age (55 years). The proportion of clear cell histology was significantly higher in Asians versus Whites, Blacks, and others (11.1% versus 4.8%, 3.1%, and 5.5%; p<0.001). Clear cell carcinoma is more likely to be diagnosed at early-stage (67.3%) compared to 19.2% in serous, 61.6% endometrioid, and 61.3% in mucinous carcinomas (p<0.005). Retroperitoneal lymph node metastases were found in 13.6% of serous carcinomas, 7.9% clear cell, 7.3% endometrioid, and 3.8% of mucinous (p<0.001). Adjusted for stage, the 5-year disease-specific survival of patients with clear cell carcinoma is worse compared to serous: 85.3% vs. 86.4% for stage I, 60.3% vs. 66.4% stage II, 31.5% vs. 35.0% stage III, and 17.5% vs. 22.2% for stage IV, respectively (p<0.001). On multivariate analysis, age, stage, grade, histology, and surgical treatment were independent predictors of disease-specific survival. CONCLUSIONS Our data suggest that women with clear cell ovarian cancer present at a younger age, are more likely to be Asian, and have a poorer prognosis compared to serous cancers.

Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths.

OBJECTIVE The purpose of this study was to determine factors responsible for the increasing number of deaths from corpus cancer over three time periods. STUDY DESIGN Data were collected from the Surveillance, Epidemiology and End Results database from 1988-2001. Kaplan-Meier and Cox proportional hazards regression analyses were performed. RESULTS Of 48,510 women with corpus cancer, there was an increase in the proportion of patients dying from advanced cancers (52.1% to 56.0% to 68.8%; P < .001), grade 3 disease (47.5% to 53.3% to 60.6%; P < .001), serous tumors (14.3% to 18.4% to 16.6%; P < .001), and sarcomas (19.1% to 20.4% to 27.2%; P < .001) over time. On multivariate analysis, older age, African American race, lack of primary staging procedures, advanced-stage, high-grade, and non-endometrioid histology were independent prognostic factors for worse survival. CONCLUSION Our data suggest that the increase in mortality in women with corpus cancer over the last 14 years may be related to an increased rate of advanced-stage cancers and high-risk histologies.

Endometrial stromal sarcoma: a population-based analysis

To determine independent prognostic factors for the survival of patients with endometrial stromal sarcoma (ESS), data were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute from 1988 to 2003. Kaplan–Meier and Cox proportional hazards models were used for analyses. Of 831 women diagnosed with ESS, the median age was 52 years (range: 17–96 years). In total, 59.9% had stage I, 5.1% stage II, 14.9% stage III, and 20.1% had stage IV disease. Overall, 13.0, 36.1, and 34.7% presented with grades 1, 2, and 3, respectively. Patients with stage I–II vs III–IV disease had 5 years DSS of 89.3% vs 50.3% (P<0.001) and those with grades 1, 2, and 3 cancers had survivals of 91.4, 95.4, and 42.1% (P<0.001). In multivariate analysis, older patients, black race, advanced stage, higher grade, lack of primary surgery, and nodal metastasis were independent prognostic factors for poorer survival. In younger women (<50 years) with stage I–II disease, ovarian-sparing procedures did not adversely impact survival (91.9 vs 96.2%; P=0.1). Age, race, primary surgery, stage, and grade are important prognostic factors for ESS. Excellent survival in patients with grade 1 and 2 disease of all stages supports the concept that these tumors are significantly different from grade 3 tumors. Ovarian-sparing surgeries may be considered in younger patients with early-stage disease.

Prevalence and Significance of Fluoroquinolone Resistant Escherichia coli in Patients Undergoing Transrectal Ultrasound Guided Prostate Needle Biopsy

PURPOSE We estimated the prevalence of fluoroquinolone resistant Escherichia coli in patients undergoing repeat transrectal ultrasound guided prostate needle biopsy and identified high risk groups. MATERIALS AND METHODS From January 2009 to March 2010 rectal swabs of 136 men from 3 institutions undergoing transrectal ultrasound guided prostate needle biopsy were obtained. There were 33 men with no previous biopsy who served as the controls. Participants completed questionnaires and rectal swab culture was obtained just before performing the prostate biopsy. Selective media was used to specifically isolate fluoroquinolone resistant E. coli and sensitivities were obtained. The patients were contacted via telephone 7 days after the procedure for a followup questionnaire. RESULTS A total of 30 patients had cultures positive for fluoroquinolone resistant bacteria for an overall rate of 22% (95% CI 15, 29). Patients with diabetes and Asian ethnicity had higher risks of resistant rectal flora colonization (OR 2.3 and 2.8, respectively). However, differences did not reach statistical significance (p = 0.09 and p = 0.08, respectively). Patients with no prior biopsy had a positive rate of 15% (5 of 33) compared to 24% (25 of 103) in those with 1 or more prior biopsies (OR 1.8, p = 0.27). Five patients (3.6%) had post-biopsy fever while only 1 of those patients had a positive rectal swab. CONCLUSIONS Using selective media to isolate fluoroquinolone resistant E. coli from the rectum before transrectal ultrasound guided prostate biopsy, we isolated organisms in 22% of patients with a wide resistance pattern. This protocol may be used to provide information regarding targeted antibiotic prophylaxis before transrectal prostate biopsies.

Significance of comprehensive surgical staging in noninvasive papillary serous carcinoma of the endometrium.

OBJECTIVE To evaluate the biological behavior of noninvasive papillary serous carcinoma of the endometrium. METHODS; From 1990 to 2001, all women with noninvasive uterine papillary serous carcinoma (UPSC) at three Southern California hospitals were identified from tumor registry databases. Data for analysis were collected from hospital charts, office records, and tumor registry files. RESULTS Of the 100 patients diagnosed with UPSC, 16 had noninvasive lesions. Twelve underwent a comprehensive surgical staging procedure with omental resection. Six of these 12 women were found to have disease beyond the uterine corpus, including 4 with adnexal involvement, 3 with omental disease, 2 with cervical extension, 1 with pelvic lymph node involvement, and 3 with positive washings. Three women were found to have positive cytology and metastases in more than one location. Of the 12 patients, 1 of the 6 with stage IA disease had distant recurrence and 4 of the 6 with stage II-IV disease recurred. Of the remaining 4 patients who underwent a staging procedure without pathologic omental assessment, 1 was found to have cervical extension. In these 4 women, 1 with stage IA disease recurred. CONCLUSION The typical patterns of spread and prognostic factors for endometrioid carcinoma of the uterus do not apply to UPSC. In our series, omental assessment was necessary to detect the 25% of patients with stage IVB disease due to omental involvement. Thus, women with noninvasive UPSC should undergo a comprehensive staging procedure including omental sampling to determine the extent of disease.