Citations

AbstractLeukemia-cell expression of ZAP-70, CD38, or unmutated immunoglobulin heavy chain variable region genes (U-IGHV) each is associated with aggressive disease in patients with chronic lymphocytic leukemia (CLL). To assess the relative strength of each marker, we defined thresholds for designating a case as positive for CD38 or ZAP-70 in a test cohort of 307 patients and used these data-defined criteria to stratify patients in an independent cohort of 705 patients. Multivariable analysis revealed that ZAP-70 was the strongest risk factor. Knowledge of the IGHV mutation status or CD38 did not improve our ability to predict the time to first treatment except for ZAP-70–negative cases, which could be segregated into 2 groups of intermediate-risk or low-risk disease based on whether they expressed unmutated or mutated IGHV. ZAP-70 maintained its high relative prognostic value for the subset of patients with early-stage, asymptomatic disease, including patients evaluated within 1 year of diagnosis. Although it is premature to recommend therapy based on these risk factors, patients with ZAP-70–positive CLL cells should be monitored closely for disease progression as they have a median time from diagnosis to requiring initial therapy by standard criteria of approximately 3 years.

AbstractRecent studies have shown the importance of helper CD4 T cells in initiating and sustaining tumor-specific CD8 T-cell immunity. This has paved the way for identifying MHC class II epitopes that could be incorporated into class I–based vaccines. In this study, the goal was to identify an HLA-DR–degenerate epitope pool derived from insulin-like growth factor binding protein 2 (IGFBP-2). IGFBP-2, a regulator of insulin-like growth factor action, is overexpressed in the majority of breast and ovarian cancers. Using algorithms, we predicted 29 HLA-DR1–binding epitopes. Binding assays targeting 15 different HLA-DRs revealed that 10 epitopes were degenerate, binding to at least four different HLA-DR variants. An IFN-γ enzyme-linked immunosorbent spot assay was used to assess immunity to these 10 epitopes in 48 patients with either breast or ovarian cancer and 18 controls. Elevated T-cell immunity in patients was detected in 4 of the 10 epitopes (IGFBP2.17, IGFBP2.22, IGFBP2.249, and IGFBP2.293). The cumulative T-cell frequency of these four epitopes was elevated in patients relative to controls. All four peptides are naturally processed and presented to CD4 T-cells. The degenerate pool of peptides covers nearly 80% of patients and may be useful for augmenting CD4 T-cell immunity in patients undergoing immunization. [Cancer Res 2008;68(12):4893–901]

Study Design and SettingA two‐center prospective case series analysis.PatientsOne hundred fourteen patients with previously treated laryngeal or pharyngeal squamous cell carcinoma who underwent salvage transoral laser microsurgery (TLM).InterventionsTLM in 114 patients, neck dissection in 22 (19%) patients, adjuvant radiotherapy in 12 (11%) patients.ResultsNinety‐one (80%) patients had recurrent primary tumors whereas 23 (20%) patients had second primary tumors occur within a previously irradiated field. The minimum follow‐up was 1 year (median, 3 years). The distribution of tumor location was oropharynx 52 (46%), glottic and subglottic larynx 44 (39%), supraglottic larynx 11 (10%), and pyriform/hypopharynx 7 (6%). Overall, three‐year local and locoregional control estimates were 70 percent and 67 percent, respectively; and three‐year survival and disease‐free survival estimates were 62 percent and 64 percent, respectively. The average duration of hospitalization was 2.3 days. Four (3.5%) patients had significant postoperative bleeding. Two (<2%) patients had treatment‐related deaths.ConclusionsTransoral laser microsurgery offers select patients an attractive alternative salvage surgical therapy to the recurrent and second primary tumor site.

ABSTRACT Introduction Sexual function through pregnancy and the postpartum period is an important aspect of quality of life. Despite this, prospective studies are limited, and the impact of body image on sexual function has not been explored. Aim To prospectively assess the effects of pregnancy on sexual function, and explore causative factors for sexual function alterations such as body image and pelvic floor symptoms. Materials and Methods Pregnant women completed the questionnaires in the first and third trimester and at 6 months postpartum. These included general information, questions regarding sexual activity and practices, and five validated indices: the Female Sexual Function Index (FSFI), the Body Exposure during Sexual Activities Questionnaire, short forms of Urogenital Distress Inventory and Incontinence Impact Questionnaire, and the Fecal Incontinence Quality of Life Scale. Main Outcome Measures An assessment of the FSFI domains through the 6 months postpartum and relationships between sexual function, body image, and pelvic floor symptoms. Results One hundred seven women were enrolled, 63 completed the final questionnaire. Sexual function declined through pregnancy and was not recovered by postpartum (P = 0.017); sexual frequency was highest prior to becoming pregnant (P &lt; 0.0005). Sexual practices changed during pregnancy but returned to early pregnancy levels in the postpartum period. Although body image during sexual functioning did not significantly change during pregnancy, it worsened in the postpartum period (P = 0.01). In early pregnancy, low sexual function was associated with impaired body image, while in the postpartum period, worse urinary symptoms correlated with poor FSFI. Conclusion Sexual function worsens during pregnancy and is not recovered by the 6 months postpartum; poor scores may be attributable to low body image and urinary complaints.

Object Approximately 20% of patients with an intracranial saccular aneurysm report a family history of intracranial aneurysm (IA) or subarachnoid hemorrhage. A better understanding of predictors of aneurysm detection in familial IA may allow more targeted aneurysm screening strategies. Methods The Familial Intracranial Aneurysm (FIA) study is a multicenter study, in which the primary objective is to define the susceptibility genes related to the formation of IA. First-degree relatives (FDRs) of those affected with IA are offered screening with magnetic resonance (MR) angiography if they were previously unaffected, are ≥ 30 years of age, and have a history of smoking and/or hypertension. Independent predictors of aneurysm detection on MR angiography were determined using the generalized estimating equation version of logistic regression. Results Among the first 303 patients screened with MR angiography, 58 (19.1%) had at least 1 IA, including 24% of women and 11.7% of men. Ten (17.2%) of 58 affected patients had multiple aneurysms. Independent predictors of aneurysm detection included female sex (odds ratio [OR] 2.46, p = 0.001), pack-years of cigarette smoking (OR 3.24 for 20 pack-years of cigarette smoking compared with never having smoked, p < 0.001), and duration of hypertension (OR 1.26 comparing those with 10 years of hypertension to those with no hypertension, p = 0.006). Conclusions In the FIA study, among the affected patients' FDRs who are > 30 years of age, those who are women or who have a history of smoking or hypertension are at increased risk of suffering an IA and should be strongly considered for screening.