Cytokeratin immunohistochemistry improves interobserver variability between unskilled pathologists in the evaluation of tumor budding in T1 colorectal cancer.

Tumor budding is a major risk factor for T1 colorectal cancer. Quality control of the pathological diagnosis of budding is crucial, irrespective of the pathologist's experience. This study examines the interobserver variability according to pathologists' experience and evaluates the influence of cytokeratin (CK) immunostaining in the assessment of budding. Hematoxylin-eosin (HE) and CK-immunostained slides of 40 cases with T1 primary colorectal cancer were examined. Budding grades were individually evaluated by 12 pathologists who we categorized into three groups by their experience (expert, with >10 years of experience (n = 4), senior, with 5-10 years (n = 4), and junior, < 5 years (n = 4)). The results revealed a tendency for the more experienced pathologists to assign higher budding grades compared to the less-experienced pathologists. In the junior group, the interobserver variability obtained with HE slides was poor, but it was markedly improved in the evaluation using CK-immunostained slides. The benefit of CK immunostaining was only slight in the expert group. CK immunostaining would be useful when a pathologist is not experienced enough or does not have enough confidence in the assessment of budding.

Changes in foveal thickness after vitrectomy for macular edema with branch retinal vein occlusion and intravitreal vascular endothelial growth factor.

Purpose To examine the outcome of vitrectomy for macular edema associated with branch retinal vein occlusion (BRVO) and determine the relationship between the severity of macular edema and the concentration of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in the vitreous fluid. Design Prospective observational case series. Patients and Methods Thirty-four consecutive patients (34 eyes) with macular edema associated with BRVO underwent vitrectomy. Retinal thickness was examined using optical coherence tomography. VEGF and IL-6 levels in the vitreous fluid were determined by enzyme-linked immunosorbent assay. The patients were followed for 6 months and longer after surgery. Results Visual acuity and the retinal thickness at 6 months after operation were significantly improved (P = 0.0042 and P < 0.0001, respectively). There was a significant positive correlation between the vitreous levels of VEGF and improved level of the severity of macular edema. The vitreous levels of VEGF were significantly higher in patients who showed greater improvement in the severity of macular edema (r = 0.4277, P = 0.0116). The vitreous levels of IL-6 were not significantly correlated with improvement in the severity of macular edema (r = 0.1996, P = 0.2578). Conclusion Vitrectomy appears effective for treatment of macular edema with BRVO. A higher VEGF level in the vitreous fluid may be associated with greater improvement of macular edema with BRVO.

Developing an instrument to measure climacteric symptoms among Korean and Japanese women.

PURPOSE: The purpose of this study was to construct a measurement instrument for climacteric symptoms among Korean and Japanese women. METHODS: From Dec. 1st of 2003 to March 30th of 2004, in-depth interviews were made with 26 women (15 in Jinju, Korea and 11 in Nagasaki, Japan) aged from 45 to 59 years who had not taken hormone replacement therapy to relieve the climacteric symptoms. A draft questionnaire with 45 items was constructed on the basis of the interview data and literature review. Three obstetricians, three PhDs in nursing science, and a chief nurse who was exclusively in charge of the climacteric management, examined the draft questionnaire to evaluate content validity. After deletions 39 items remained for a preliminary questionnaire. A survey was conducted by using a convenient sampling method in Jinju of Korea and Nagasaki of Japan during the period from April 1st, 2004 to July 10th, 2005. RESULTS: Factor analysis identified 4 factors, which were "mental and psychological symptoms", "physical symptoms", "loss of autonomic nervous system symptoms", "sexual symptoms". These four factors explained 46.9% of total variance. CONCLUSIONS: The results demonstrated that climacteric symptom scale was multidimensional, and the reliability and validity of the scale was supported.

Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6.

PURPOSE: To determine whether correlations between vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contribute to the pathogenesis of macular edema in eyes of patients with branch retinal vein occlusion (BRVO). DESIGN: Retrospective case-control study. METHODS: Nineteen patients with macular edema with BRVO and seven patients with non-ischemic ocular disease (control group) were studied. The degree of retinal ischemia was evaluated in terms of the area of capillary non-perfusion, and the severity of macular edema was examined by optical coherence tomography. Aqueous humor samples were obtained at the time of combined vitrectomy and cataract surgery, and VEGF and IL-6 levels in aqueous humor and plasma were determined by enzyme-linked immunosorbent assay. RESULTS: Aqueous levels of VEGF (351 +/- 273 pg/ml) and IL-6 (7.10 +/- 6.51 pg/ml) were significantly elevated in patients with BRVO compared with the control patients (119 +/- 38.7 pg/ml and 2.27 +/- 1.11 pg/ml, respectively) (P = .0017 and P = .0052, respectively). Aqueous level of VEGF was significantly correlated with that of IL-6 (P = .0396), and aqueous levels of VEGF and IL-6 were correlated with the size of the BRVO non-perfused area (P < .0001 and P = .0331, respectively). Aqueous level of VEGF was correlated with the severity of macular edema (P = .0306). CONCLUSIONS: VEGF and IL-6 may be involved in the pathogenesis of macular edema with BRVO. The increase in these cytokines might be used as a unique index of BRVO, through which we can determine the severity of the ischemic condition as being in a quiescent state or an exacerbation of macular edema.

Neuroprotective effects of erythropoietin on glutamate and nitric oxide toxicity in primary cultured retinal ganglion cells.

Erythropoietin receptor (EpoR) is expressed in the central nervous system (CNS), however, no clear consensus has been obtained whether Epo acts as a prosurvival factor in neurons. Because retinal ganglion cell (RGC) death is a common cause of reduced visual function in several ocular diseases, we explored whether Epo might potentially be beneficial in protecting RGCs from glutamate and nitric oxide (NO)-induced cytotoxicity, using isolated RGCs by a two-step panning method. Brain-derived neurotrophic factor (BDNF) was used as a positive control. EpoR mRNA was expressed in isolated RGCs, and EpoR protein was expressed on the RGCs in the normal and ischemic retinas. Epo had less potential to improve the survival of primary RGCs in serum-free medium than BDNF. In these cells, BDNF, but not Epo, downregulated the expression of Bim, a proapoptotic Bcl-2 family member that plays a key role in cytokine-mediated cell survival, suggesting a possible mechanism for this difference. When RGCs were cultured with glutamate or an NO-generating reagent, the survival of RGCs was compromised, and Bcl-2 expression was decreased in these cells. Both Epo and BDNF significantly reduced RGC death induced by glutamate and NO. In agreement with this, these factors reversed the Bcl-2 expression. These findings suggest that Epo may be a potent neuroprotective therapeutic agent for the treatment of ocular diseases that are characterized by RGC death.

The negative correlation between age and intraocular pressures measured nyctohemerally in elderly normal-tension glaucoma patients.

PURPOSE: To evaluate the correlation between age and intraocular pressure (IOP) measured every 3 h for 24 h in older normal-tension glaucoma (NTG) patients. METHODS: Ninety consecutive patients suspected of having NTG on the basis of both visual field defect and disc appearance were hospitalized for measurement of nyctohemeral IOP every 3 h over a 24-h period with a Goldmann tonometer after a 4-week wash-out of any existing medication. Sixty-nine patients (76.7%) were diagnosed as having NTG. Sixty-nine eyes of 69 subjects were enrolled for this prospective, cross-sectional study. They were divided into two groups by age (cut-off between 59 and 60 years: group 1, under 60 years; group 2, over 60 years). The correlations between age and the mean, maximum and minimum IOP and IOP variation of the eight nyctohemeral IOP measurements nyctohemerally were evaluated for each group. The times of day at which the maximum and minimum IOPs were observed were recorded. RESULTS: Groups 1 and 2 consisted of 28 patients (age: 50.2+/-6.1 years) and 42 patients (age: 70.3+/-6.1 years) ( P<0.0001), respectively. Neither mean, maximum or minimum IOP nor the IOP variation was significantly different between the groups (all P values > or =0.115). The mean, maximum and minimum IOP in group 2 were all correlated with age ( n=41; r=-0.516, P=0.0004; r=-0.434, P=0.004; r=-0.522, P=0.0004, respectively), while none of those in group 1 was correlated with age (all P values > or =0.303). CONCLUSION: The IOPs of the elder NTG patients have a negative correlation with age while those of the younger ones have no relation to age.