Metabolic syndrome, dyslipidemia and prostate cancer recurrence after primary surgery or radiation in a veterans cohort.

BACKGROUND: Metabolic syndrome (MetS) has been hypothesized to be associated with cancer, including prostate cancer (PCa), but the relationship is not well characterized. We analyze the relationship between MetS features and localized PCa recurrence after treatment. METHODS: Men having primary treatment for localized PCa were included from a multi-site regional veteran network. Recurrence was defined as nadir PSA +2 ng ml(-1) (radiation) or PSA⩾0.2 ng ml(-1) (prostatectomy). MetS was based on consensus professional society guidelines from the American Heart Association and International Diabetes Federation (three of: hypertension >130/85 mm Hg, fasting blood glucose ⩾100 mg dl(-1), waist circumference >102 cm, high-density lipoprotein <40 mg dl(-1), triglycerides ⩾150 mg dl(-1)). Closely related abnormality in low-density lipoprotein (LDL; >130 mg dl(-1)) was also examined. Analysis of PCa recurrence risk included multivariable Cox proportional hazards regression with propensity adjustment. RESULTS: Of the 1706 eligible men, 279 experienced recurrence over a median follow-up period of 41 months (range 1-120 months). Adjustment variables associated with PCa recurrence included: index PSA, Gleason, and tumor stage. Independent variables of interest associated with PCa recurrence were hyperglycemia and elevated LDL. Elevated LDL was associated with PCa recurrence (multivariable hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.03, 1.74; propensity adjusted HR 1.33, 95% CI 1.03, 1.72). There was also an association between impaired fasting glucose and PCa recurrence in (multivariable HR 1.54, 95% CI 1.10, 2.15; propensity adjusted HR 1.41, 95% CI 1.01, 1.95). MetS was not associated with PCa recurrence (multivariable: HR 0.96, 95% CI 0.61, 1.50; propensity adjusted HR 1.04, 95% CI 0.67, 1.62). CONCLUSIONS: PCa recurrence is not associated with MetS but is associated with elevated LDL and impaired fasting glucose. If confirmed, these data may help provide modifiable targets in preventing recurrence of PCa.

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

Outcome after open reduction and internal fixation of Lisfranc joint injuries.

BACKGROUND: Open reduction and internal fixation has been recommended as the treatment for most unstable injuries of the Lisfranc (tarsometatarsal) joint. It has been thought that purely ligamentous injuries have a poor outcome despite such surgical management. METHODS: We performed a retrospective study of patients who underwent open reduction and screw fixation of a Lisfranc injury in a seven-year period. Among ninety-two adults treated for that injury, forty-eight patients with forty-eight injuries were followed for an average of fifty-two months (range, thirteen to 114 months). Fifteen injuries were purely ligamentous, and thirty-three were combined ligamentous and osseous. Patient outcome was assessed with use of the American Orthopaedic Foot and Ankle Society (AOFAS) midfoot score and the long-form Musculoskeletal Function Assessment (MFA) score. RESULTS: The average AOFAS midfoot score was 77 points (on a scale of 0 to 100 points, with 100 points indicating an excellent outcome), with patients losing points for mild pain, decreased recreational function, and orthotic requirements. The average MFA score was 19 points (on a scale of 0 to 100 points, with 0 points indicating an excellent outcome), with patients losing points because of problems with "leisure activities" and difficulties with "life changes and feelings due to the injury." Twelve patients (25 percent) had posttraumatic osteoarthritis of the tarsometatarsal joints, and six of them required arthrodesis. The major determinant of a good result was anatomical reduction (p = 0.05). The subgroup of patients with purely ligamentous injury showed a trend toward poorer outcomes despite anatomical reduction and screw fixation. CONCLUSIONS: Our results support the concept that stable anatomical reduction of fracture-dislocations of the Lisfranc joint leads to the best long-term outcomes as patients so treated have less arthritis as well as better AOFAS midfoot scores.

Reported ovarian cancer screening among a population-based sample in Washington state.

OBJECTIVE: To assess the prevalence of reported ovarian cancer screening among a population-based sample of women from Washington state and identify factors that influence the decision to be screened. METHODS: A population-based sample of 6749 women aged 54-84 years, living in 40 predominately rural communities in Washington state, was surveyed about their utilization of ultrasonography and CA 125 for ovarian cancer screening. We also assessed relevant demographic, family history, psychosocial, and health behavior variables. RESULTS: After exclusions, data from 4938 respondents were available. Two percent (n = 96) reported having been screened. Multiple logistic regression identified ovarian cancer worry, contact with an obstetrician-gynecologist, and family history of ovarian cancer as independently associated with screening. Based on self-reported family histories, 27 women had pedigrees consistent with high risk of ovarian cancer, but none of those women reported having been screened. CONCLUSION: Ovarian cancer screening is rare. Women at high risk of it might not be getting recommended screening.

Changing incidence rate of invasive lobular breast carcinoma among older women.

BACKGROUND: In 1998, an unusually large number of invasive lobular breast carcinoma cases were seen at the University of Washington. The purpose of this study was to assess whether the incidence rate of invasive lobular carcinoma has been increasing disproportionately compared with the incidence rate of invasive ductal carcinoma. METHODS: Age specific and age-adjusted breast carcinoma incidence rates from 1977-1995 were obtained from the nine population-based cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) program. Three histologic groupings were used: lobular, ductal, and all invasive breast carcinomas. Overall incidence rates for each grouping, as well as for each stage (local, regional, and distant), were obtained. RESULTS: The rate of incidence of lobular carcinoma increased steadily from 1977-1995 in women age >/= 50 years whereas it remained stable in women age < 50 years. Alternatively, the rate of incidence of ductal carcinoma increased steadily from 1977-1987, but from 1987-1995 it remained relatively constant across all age groups. CONCLUSIONS: The incidence rates of invasive lobular breast carcinomas increased steadily since 1977 whereas the incidence rates of invasive ductal carcinoma have plateaued since 1987. This rise occurred specifically among women age >/= 50 years and may be related to postmenopausal status. Further epidemiologic, clinical, and laboratory research is required to assess what factors are contributing to this trend.

[Scanning electron microscopic analysis of vessel wall reactions after coronary stenting]. / Rasterelektronenmikroskopische Analyse der reaktiven und reparativen Veränderungen humaner Koronararterien nach Stentimplantation.

High restenosis rates are still a major factor limiting the use of minimal invasive coronary stenting. Tissue reactions to the implanted alloplastic endoprostheses are still barely understood. 18 coronary artery segments 32 hours up to 340 days after stent implantation of 16 patients were post-mortem investigated. The pathomorphological findings of the vessel wall after stent insertion were studied by scanning electron microscopy (SEM). Stent integration can be divided with intraindividual differences in three phases: In the acute phase (<6 weeks) the border between vascular lumen and arterial wall is constituted by a thin, multi-layered thrombus. During the time course of integration, increasing amounts of Smooth Muscle Cells (SMC) and extracellular matrix can be detected. No endothelial cells can be found in the implantation zone. In the intermediate phase (6 weeks to 12 weeks) the neointima consists of extracellular matrix and increasing numbers of SMC. The borderline between lumen and neointima is generated by SMC and extracellular matrix. Increasing amounts of endothelial cells are found on the luminal surface of the stent neointima. Complete reendothelization is first noted in the chronic phase three months after stenting. Matrix structures are increasing whereas the amount of SMC decreases. In all phases of stent incorporation, the alloplastic stent material is covered by a thin (few nanometer) proteinaceous layer.