Five-Year Clinical Outcomes of Inferior Quadrant Trabectome Surgery for Open Angle Glaucoma.

PRCIS: This retrospective study of 264 eyes having inferior quadrant trabectome surgery confirms its safety and relative effectiveness. Most patients however still require IOP-lowering agents, and a considerable proportion may need additional glaucoma surgery. PURPOSE: To report outcomes from a large single-center cohort of inferiorly-applied trabectome surgery. PATIENTS AND METHODS: Retrospective review of patients undergoing trabectome surgery for chronic open angle glaucoma (COAG) at the University Eye Clinic Bonn, Germany, from 2012 to 2020. RESULTS: Two hundred sixty-four eyes of 206 patients with COAG were included. The mean review period was 45.43 (range 12-101) months. One hundred five eyes (39.8%) underwent standalone surgery, of which 74 were pseudophakic and 31 phakic. The mean preoperative IOP was 17.58 mm Hg (range 12-50 mm Hg). One hundred five eyes (39.8%) developed a 'failure event' according to pre-defined criteria at a mean interval of 14.8 months postoperative. In absolute terms, 211 patients (79.9%) had a long-term IOP >14 mm Hg at 7.6 months, 174 patients (65.9%) >16 mm Hg at 10.6 months, 127 patients (48.1%) >18 mm Hg at 10.9 months, and 77 patients (29.2%) >21 mm Hg at 11.1 months. Over a five-year period, overall mean IOP remained stable at 13 mm Hg. The majority of patients were still on glaucoma drops (the mean number reduced from 2.9 to 2.7 agents). Subgroup analyses showed that a higher preoperative IOP was a positive predictor for failure, whereas combined surgery (with phaco) had better IOP outcomes (16.5 mm Hg vs. 19.3 mm Hg, respectively). Forty-one patients (15.5%) developed minor complications: 22 had high postoperative IOP within 3 months, 11 developed a self-resorbing hyphema, and 6 had fibrinous uveitis. CONCLUSIONS: Trabectome surgery is a safe and relatively effective procedure for lowering IOP, but most patients still need IOP-lowering agents, and a considerable proportion may need additional glaucoma surgery within a relatively short time. Inferior quadrant treatment may result in inferior IOP outcomes when compared with nasal quadrant surgery.

Clinical Outcomes of XEN45®-Stent Implantation after Failed Trabeculectomy: A Retrospective Single-Center Study.

BACKGROUND: The implantation of a collagen gel micro-stent (XEN45®) as a minimally invasive form of glaucoma surgery (MIGS) after a failed trabeculectomy (TE) may be an effective option with few risks. This study investigated the clinical outcome of XEN45® implantation after a failed TE, with follow-up data of up to 30 months. MATERIALS AND METHODS: In this paper, we present a retrospective review of patients undergoing XEN45® implantation after a failed TE at the University Eye Hospital Bonn, Germany, from 2012 to 2020. RESULTS: In total, 14 eyes from 14 patients were included. The mean follow-up time was 20.4 months. The mean time duration between the failed TE and XEN45® implantation was 110 months. The mean intraocular pressure (IOP) decreased from 17.93 mmHg to 12.08 mmHg after one year. This value increased again to 17.63 mmHg at 24 months and 16.00 mmHg at 30 months. The number of glaucoma medications decreased from 3.2 to 0.71, 2.0, and 2.71 at 12, 24, and 30 months, respectively. CONCLUSIONS: XEN45® stent implantation after a failed TE did not lead to an effective long-term decrease in IOP and glaucoma medications in many patients in our cohort. Nevertheless, there were cases without the development of a failure event and complications, and others in whom further, more invasive surgery was delayed. XEN45® implantation in some failed trabeculectomy cases may, therefore, be a good option, especially in older patients with multiple comorbidities.

Monocyte chemoattractant protein-1 serum levels in patients with breast cancer.

The chemokine monocyte chemoattractant protein (MCP)-1 is thought to be involved in breast carcinogenesis. We evaluated MCP-1 serum levels in patients with breast cancer (n = 135), ductal carcinoma in situ (DCIS) I-III (n = 30), benign breast lesions (n = 143) and in healthy women (n = 27). We determined the value of MCP-1 serum levels as a differentiation marker between malignant, preinvasive and benign breast diseases and as a predictive marker for the biological phenotype of breast carcinoma. Median (range) MCP-1 serum levels in patients with breast cancer, DCIS I-III, benign breast lesions and healthy women were 200 (57-692) pg/ml, 194 (58-525) pg/ml, 174 (39-529) pg/ml and 175 (67-425) pg/ml, respectively. No differences were ascertained between the patient groups. In patients with breast cancer, increased MCP-1 serum levels were correlated with advanced tumor stage (p = 0.04) and lymph node involvement (p = 0.04). We were not able to establish MCP-1 as a differentiation marker between malignant and benign breast diseases. Our data might indicate that MCP-1 influences breast carcinogenesis by facilitating tumor growth and metastatic spread, thus altering the biological phenotype of the disease.

Reference values for peripheral blood lymphocyte phenotypes applicable to the healthy adult population in Switzerland.

OBJECTIVES: Use of domestic reference values is known to improve the accuracy of flow cytometric analysis by integrating local variation due to race, gender, and age. In the absence of previously published estimates, we now report establishment of reference values for a wide range of peripheral blood lymphocyte phenotypes applicable to the healthy adult population in Switzerland and other regions with similar demographic characteristics. METHODS: A representative sample population was recruited from among well characterized local blood donors (n = 70) and quantitative multiparametric flow cytometry used to estimate absolute and proportional values for a range of T-, B-, and NK-cell subsets, including those associated with activation and maturity. Distribution-free methods were then applied to generate 95% reference values and to estimate the significance of gender and age-related differences. RESULTS: Reference values were obtained for the absolute and proportional levels of total CD3(+) T cells (536-1787 cells/microL, 54.90-84.03%), helper CD4(+) T cells (309-1139 cells/microL, 32.53-62.88%), cytotoxic CD8(+) T cells (137-823 cells/microL, 11.55-38.60%), activated CD3(+) T cells expressing CD25 (7-94 cells/microL, 0.50-5.95%), CD38 (102-554 cells/microL, 5.98-26.80%), HLA-DR (18-186 cells/microL, 1.25-9.68%) or CD38/HLA-DR (4-52 cells/microL, 0.30-2.30%), activated CD4(+) T cells expressing CD25 (7-52 cells/microL, 0.33-2.80%), CD38 (69-547 cells/microL, 6.13-32.20%), HLA-DR (11-55 cells/microL, 0.80-4.43%) or CD38/HLA-DR (4-22 cells/microL, 0.30-1.35%), activated CD8(+) T cells expressing CD25 (0-12 cells/microL, 0.00-0.69%), CD38 (13-124 cells/microL, 0.93-7.03%), HLA-DR (6-108 cells/microL, 0.33-6.38%) or CD38/HLA-DR (2-47 cells/microL, 0.13-2.68%), naive CD4(+) T cells expressing CD45RA(+)/CD62L(+) (84-761 cells/microL, 9.48-41.88%), naive CD8(+) T cells expressing CD45RA(+)/CD62L(+) (42-360 cells/microL, 3.68-19.23%), memory CD4(+) T cells expressing CD45RO(+) (247-807 cells/microL, 16.50-42.15%), memory CD8(+) T cells expressing CD45RO(+) (72-377 cells/microL, 3.78-22.80%), B-cells expressing CD19 (72-460 cells/microL, 4.70-19.13%) or CD20 (66-529 cells/microL, 4.63-21.00%), total CD3(-)/(CD16(+)/CD56(+)) NK-cells (77-427 cells/microL, 5.35-30.93%), and activated NK-cells expressing CD25 (0-10 cells/microL, 0-0.50%) or HLA-DR (3-99 cells/microL, 0.20-7.28%). CONCLUSION: It is anticipated that availability of localized reference values for an extended range of peripheral blood lymphocyte phenotypes should supplement previously published reference values and enhance the utility of flow cytometric analysis undertaken in Switzerland.

Serum parameters of iron metabolism in patients with breast cancer.

BACKGROUND: The aim of our study was to determine the incidence of anemia as evidenced by altered serum levels of iron metabolism in patients with breast cancer (n = 84), ductal carcinoma in situ (DCIS) (n = 29), fibroadenoma (n = 100) and healthy women (n = 14). MATERIALS AND METHODS: Hemoglobin (Hb), serum iron, serum ferritin, serum transferrin and serum transferrin receptor were evaluated prior to surgery. No patient with breast cancer had anemia according to Hb level. RESULTS: No significant correlations between serum iron, transferrin and transferrin receptor were ascertained. Serum ferritin was significantly elevated in patients with breast cancer. Among patients with breast cancer, a significant correlation with positive lymph node involvement was noted. CONCLUSION: Elevated serum ferritin might indicate the presence of malignant disease and could be regarded as a predictor of positive lymph node involvement in patients with breast cancer.

Polymorphisms of the interleukin-1 gene cluster and ovarian cancer.

OBJECTIVE: Interleukin-1 (IL-1) is known to be critically involved in ovarian carcinogenesis. We investigated a panel of polymorphisms of the IL-1 and the IL-1 receptor antagonist (IL-1 RA) genes in patients with ovarian cancer. METHODS: One hundred thirty-four patients with surgically staged ovarian cancer, 27 patients with borderline ovarian cancer, and 134 healthy controls were genotyped for three polymorphisms of the IL-1 gene (-889 C/T polymorphism of the IL-1alpha gene [IL1A], -511 C/T polymorphism of the IL-1beta promoter [IL1B promoter], a polymorphism of IL-1beta exon 5 [IL1B exon 5]), and an 86-base pair repeat in intron 2 of the IL-1 RA gene [IL1RN]) using polymerase chain reaction and pyrosequencing. RESULTS: Allelic frequencies did not differ between patients with ovarian cancer and controls. In the ovarian cancer group, polymorphism did not correlate with any of the investigated clinicopathologic variables, including tumor stage, lymph node, and histologic grade. In univariate and multivariate models, there was no correlation between any polymorphism and patients' overall and disease-free survival. CONCLUSION: We investigated interleukin polymorphisms in ovarian cancer but did not find any association between common polymorphisms of IL1A, IL1B, and IL1RN and the occurrence of ovarian cancer. Allelic variation within the IL-1 gene clusters does not seem to play a role in ovarian carcinogenesis and does not appear to be a useful tool for possible screening and risk evaluation.

The use of anti-T-cell receptor-Vbeta antibodies for the estimation of treatment success and phenotypic characterization of clonal T-cell populations in cutaneous T-cell lymphomas.

Sézary syndrome and Mycosis fungoides are the most common forms of cutaneous T-cell lymphomas. To assess the response to different therapies especially in Sézary syndrome, it is helpful to monitor the percentage of circulating tumour cells in the blood. The use of T-cell receptor (TCR)-Vbeta specific monoclonal antibodies provides a suitable tool for detecting Sézary cells. In this study, we analysed the levels of clonal CD4+Vbeta+ cells of seven patients with various treatment modalities using flow cytometry and investigated the immunophenotype of the clonal cells by double staining with a panel of antibodies recognizing lymphatic surface markers. Additionally, a polymerase chain reaction-denaturing gradient gel electrophoresis assay was performed on clonal CD4+Vbeta2+ cells, showing that these cells carry a Vgamma10/11, JgammaP1/2 TCR rearrangement. Follow-up studies revealed close association of the Vbeta+ clone developmentwith the clinical response to different therapiesinsixpatients. Intwo cases, the CD4+Vbeta+ cells decreased accompanied by partial regression or even complete remission. In four cases, a stable or increasing clonal CD4+Vbeta+ population reflected well a stable or progressing course of the disease. Double staining of Vbeta+ cells revealed the following pattern, CD3+, CD5+, CD7+, CD28+, CD80-, CD86+ and human leucocyte antigen (HLA) class I+. In contrast, HLA-DR was heterogeneously expressed. We conclude that identification and monitoring of CD4+Vbeta+ clonal T cells by fluorescence-activated cell sorting with double staining is a suitable method to assess clinical responses to different therapies.

Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer.

OBJECTIVE: The free radical nitric oxide is known to be critically involved in ovarian carcinogenesis by inducing apoptosis and by mediating various cytostatic and cytotoxic effects, but also by promoting growth, invasion, and metastasis. METHODS: We investigated two polymorphisms (exon 7 Glu298Asp and a 27-bp repeat in intron 4) of the gene encoding endothelial nitric oxide synthase (Nos3) in 130 patients with ovarian cancer, 26 patients with borderline ovarian cancer, and 133 healthy age-matched Caucasian women using PCR and pyrosequencing, respectively. RESULTS: Genotypes and allelic frequencies did not differ between patients with ovarian cancer and controls. Within the ovarian cancer group, however, the presence of at least one mutant allele of intron 4 was associated with advanced tumor stage and positive lymph node involvement, but not with tumor grading. The presence of the mutant allele of exon 7 was not associated with the investigated clinicopathological parameters. No correlation with patients' overall and disease-free survival was ascertained. CONCLUSIONS: We are the first to report on Nos3 polymorphisms in ovarian cancer. Allelic variation within intron 4 of Nos3 is associated with an advanced tumor stage and positive lymph node involvement in ovarian cancer.

Serum vascular endothelial growth factor and serum leptin in patients with cervical cancer.

OBJECTIVE: Serum levels of vascular endothelial growth factor (VEGF) can be seen as surrogate markers of angiogenesis. Recently, leptin, which is involved in the control of satiety and energy expenditure, was also shown to modulate angiogenesis. As angiogenesis plays an abundant role in cervical carcinogenesis, we evaluated serum VEGF and leptin in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: Serum VEGF and leptin were measured in 84 patients with cervical cancer, in 28 patients with CIN I-III, and in 35 healthy women, using a commercially available enzyme-linked immunosorbent assay and radioimmunoassay, respectively. RESULTS: Serum VEGF was significantly elevated in patients with cervical cancer and in patients with CIN I-III compared to healthy women. In patients with cervical cancer serum VEGF was significantly correlated with tumor stage, but not with lymph node involvement and histological grade. Univariate and multivariate analyses showed that elevated pretreatment serum VEGF was not associated with the duration of disease-free and overall survival. Serum leptin did not differ among patients with cervical cancer, patients with CIN I-III, and healthy women. Serum leptin was significantly correlated with body mass index (BMI). All further analyses were performed with absolute and serum leptin corrected by BMI. No differences in serum leptin could be ascertained between patients with cervical cancer and patients with CIN I-III. Serum leptin was not associated with any clinicopathological parameter and patients' survival. No correlation between serum VEGF and leptin was found. CONCLUSIONS: It can be speculated that serum VEGF might be used as a surrogate marker of angiogenesis in patients with cervical cancer. Our data support the concept that VEGF plays a role in malignant transformation and tumor growth, but not in the lymphatic spread of cervical cancer. This is the first report on leptin in a gynecological malignancy. Our results show that serum leptin falls short of being a useful marker in patients with cervical cancer.